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Regenerative Medicine - from Protocol to Patient pp 389–424Cite as

Cell Programming for Future Regenerative Medicine

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Abstract

Numerous diseases are characterized by malfunction of key cells or their faulty integration within highly complex organ systems. Intense research over the last decade has led to a better understanding of these disorders on the molecular level. This is an indispensable prerequisite for restoring the functionality of the affected organs, representing the first and foremost aim of the rapidly developing field of regenerative medicine. However, adult organs exhibit limited self-renewal capacity and often cannot accomplish a functional restoration on their own. Therefore, new strategies are currently being considered for cell programming based replacement therapies as well as for disease modelling and drug development. Before the discovery that somatic cells could be either reprogrammed to a pluripotent state or directly converted to other somatic cell types, the regenerative field was hampered by ethical concerns connected to human embryonic stem cells as well as by restricted availability of adult stem cells. Meanwhile, several strategies based on the introduction of lineage specific transcription factors, mRNAs, microRNAs and small molecules have opened up new perspectives for safe and efficient generation of induced pluripotent stem cells (iPSCs) as well as various specified somatic cell types. The foremost priority should be the generation of fully functional cells with characteristics as close as possible to their natural counterparts. Furthermore, the production of clinically relevant numbers of healthy cells as well as cells with defined disease patterns could provide an important link between basic research, drug screening and safety testing and ultimately clinical trials. In this article we summarize the remarkable recent successes in cellular reprogramming, which have highly contributed to the great progress of regenerative medicine over the last years.

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References

  • Aikawa N, Suzuki Y, Takaba K (2015) A simple protocol for the myocardial differentiation of human iPS cells. Biol Pharm Bull 38(7):1070–1075

    Article  CAS  PubMed  Google Scholar 

  • Anderson ME, Goldhaber J, Houser SR, Puceat M, Sussman MA (2014) Embryonic stem cell-derived cardiac myocytes are not ready for human trials. Circ Res 115(3):335–338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Araki R, Uda M, Hoki Y, Sunayama M, Nakamura M, Ando S, Sugiura M, Ideno H, Shimada A, Nifuji A, Abe M (2013) Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature 494(7435):100–104

    Article  CAS  PubMed  Google Scholar 

  • Ashcroft FM, Rorsman P (2012) Diabetes mellitus and the β cell: the last ten years. Cell 148(6):1160–1171

    Article  CAS  PubMed  Google Scholar 

  • Atkinson SP, Lako M, Armstrong L (2013) Potential for pharmacological manipulation of human embryonic stem cells. Br J Pharmacol 169(2):269–289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banga A, Akinci E, Greder LV, Dutton JR, Slack JMW (2012) In vivo reprogramming of Sox9+ cells in the liver to insulin-secreting ducts. Proc Natl Acad Sci U S A 109(38):15336–15341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barad L, Schick R, Zeevi-Levin N, Itskovitz-Eldor J, Binah O (2014) Human embryonic stem cells vs human induced pluripotent stem cells for cardiac repair. Can J Cardiol 30(11):1279–1287

    Article  PubMed  Google Scholar 

  • Bar-Nur O, Russ HA, Efrat S, Benvenisty N (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 9(1):17–23

    Article  CAS  PubMed  Google Scholar 

  • Basma H, Soto-Gutiérrez A, Yannam GR, Liu L, Ito R, Yamamoto T, Ellis E, Carson SD, Sato S, Chen Y, Muirhead D, Navarro-Alvarez N, Wong RJ, Roy-Chowdhury J, Platt JL, Mercer DF, Miller JD, Strom SC, Kobayashi N, Fox IJ (2009) Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology 136(3):990–999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Batta K, Florkowska M, Kouskoff V, Lacaud G (2014) Direct reprogramming of murine fibroblasts to hematopoietic progenitor cells. Cell Rep 9(5):1871–1884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benevento M, Tonge PD, Puri MC, Hussein SMI, Cloonan N, Wood DL, Grimmond SM, Nagy A, Munoz J, Heck AJR (2014) Proteome adaptation in cell reprogramming proceeds via distinct transcriptional networks. Nat Commun 5:5613

    Article  CAS  PubMed  Google Scholar 

  • Benraiss A, Toner MJ, Xu Q, Bruel-Jungerman E, Rogers EH, Wang F, Economides AN, Davidson BL, Kageyama R, Nedergaard M, Goldman SA (2013) Sustained mobilization of endogenous neural progenitors delays disease progression in a transgenic model of Huntington’s disease. Cell Stem Cell 12(6):787–799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisen J (2009) Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brade T, Pane LS, Moretti A, Chien KR, Laugwitz K-L (2013) Embryonic heart progenitors and cardiogenesis. Cold Spring Harb Perspect Med 3(10):a013847

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bressan M, Liu G, Mikawa T (2013) Early mesodermal cues assign avian cardiac pacemaker fate potential in a tertiary heart field. Science 340(6133):744–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruneau BG, Nemer G, Schmitt JP, Charron F, Robitaille L, Caron S, Conner DA, Gessler M, Nemer M, Seidman CE, Seidman JG (2001) A murine model of holt-oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell 106(6):709–721

    Article  CAS  PubMed  Google Scholar 

  • Buckingham M, Meilhac S, Zaffran S (2005) Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet 6(11):826–835

    Article  CAS  PubMed  Google Scholar 

  • Budniatzky I, Gepstein L (2014) Concise review: reprogramming strategies for cardiovascular regenerative medicine: from induced pluripotent stem cells to direct reprogramming. Stem Cells Transl Med 3(4):448–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai W, Albini S, Wei K, Willems E, Guzzo RM, Tsuda M, Giordani L, Spiering S, Kurian L, Yeo GW, Puri PL, Mercola M (2013) Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment. Genes Dev 27(21):2332–2344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caiazzo M, Dell’Anno MT, Dvoretskova E, Lazarevic D, Taverna S, Leo D, Sotnikova TD, Menegon A, Roncaglia P, Colciago G, Russo G, Carninci P, Pezzoli G, Gainetdinov RR, Gustincich S, Dityatev A, Broccoli V (2011) Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 476(7359):224–227

    Article  CAS  PubMed  Google Scholar 

  • Caprioli A, Koyano-Nakagawa N, Iacovino M, Shi X, Ferdous A, Harvey RP, Olson EN, Kyba M, Garry DJ (2011) Nkx2-5 represses Gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis. Circulation 123(15):1633–1641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carpenter L, Carr C, Yang CT, Stuckey DJ, Clarke K, Watt SM (2012) Efficient differentiation of human induced pluripotent stem cells generates cardiac cells that provide protection following myocardial infarction in the rat. Stem Cells Dev 21(6):977–986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caspi O, Huber I, Kehat I, Habib M, Arbel G, Gepstein A, Yankelson L, Aronson D, Beyar R, Gepstein L (2007) Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol 50(19):1884–1893

    Article  PubMed  Google Scholar 

  • Chen C-Z, Li L, Lodish HF, Bartel DP (2004a) MicroRNAs modulate hematopoietic lineage differentiation. Science 303(5654):83–86

    Article  CAS  PubMed  Google Scholar 

  • Chen S-L, Fang W-W, Ye F, Liu Y-H, Qian J, Shan S-J, Zhang J-J, Chunhua RZ, Liao L-M, Lin S, Sun J-P (2004b) Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 94(1):92–95

    Article  PubMed  Google Scholar 

  • Chen JX, Krane M, Deutsch M-A, Wang L, Rav-Acha M, Gregoire S, Engels MC, Rajarajan K, Karra R, Abel ED, Wu JC, Milan D, Wu SM (2012) Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5. Circ Res 111(1):50–55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng L, Hu W, Qiu B, Zhao J, Yu Y, Guan W, Wang M, Yang W, Pei G (2014) Generation of neural progenitor cells by chemical cocktails and hypoxia. Cell Res 24(6):665–679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chong JJH, Yang X, Don CW, Minami E, Liu Y-W, Weyers JJ, Mahoney WM, van Biber B, Cook SM, Palpant NJ, Gantz JA, Fugate JA, Muskheli V, Gough GM, Vogel KW, Astley CA, Hotchkiss CE, Baldessari A, Pabon L, Reinecke H, Gill EA, Nelson V, Kiem H-P, Laflamme MA, Murry CE (2014) Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510(7504):273–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clancy JL, Patel HR, Hussein SMI, Tonge PD, Cloonan N, Corso AJ, Li M, Lee D-S, Shin J-Y, Wong JJL, Bailey CG, Benevento M, Munoz J, Chuah A, Wood D, Rasko JEJ, Heck AJR, Grimmond SM, Rogers IM, Seo J-S, Wells CA, Puri MC, Nagy A, Preiss T (2014) Small RNA changes en route to distinct cellular states of induced pluripotency. Nat Commun 5:5522

    Article  CAS  PubMed  Google Scholar 

  • Cooke JP, Sayed N, Lee J, Wong WT (2014) Innate immunity and epigenetic plasticity in cellular reprogramming. Curr Opin Genet Dev 28:89–91

    Article  CAS  PubMed  Google Scholar 

  • Cyranoski D (2014) Japanese woman is first recipient of next-generation stem cells. Nature News. Nature Publishing Group. http://www.nature.com/news/japanese-woman-is-first-recipient-of-next-generation-stemcells-1.15915

  • David R, Brenner C, Stieber J, Schwarz F, Brunner S, Vollmer M, Mentele E, Müller-Höcker J, Kitajima S, Lickert H, Rupp R, Franz W-M (2008) MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling. Nat Cell Biol 10(3):338–345

    Article  CAS  PubMed  Google Scholar 

  • David R, Stieber J, Fischer E, Brunner S, Brenner C, Pfeiler S, Schwarz F, Franz W-M (2009) Forward programming of pluripotent stem cells towards distinct cardiovascular cell types. Cardiovasc Res 84(2):263–272

    Article  CAS  PubMed  Google Scholar 

  • David R, Jarsch VB, Schwarz F, Nathan P, Gegg M, Lickert H, Franz W-M (2011) Induction of MesP1 by Brachyury(T) generates the common multipotent cardiovascular stem cell. Cardiovasc Res 92(1):115–122

    Article  CAS  PubMed  Google Scholar 

  • Davis RL, Weintraub H, Lassar AB (1987) Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell Press 51(6):987–1000

    CAS  Google Scholar 

  • de Feo D, Merlini A, Laterza C, Martino G (2012) Neural stem cell transplantation in central nervous system disorders: from cell replacement to neuroprotection. Curr Opin Neurol 25(3):322–333

    Article  PubMed  CAS  Google Scholar 

  • de Val S, Black BL (2009) Transcriptional control of endothelial cell development. Dev Cell 16(2):180–195

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigó R (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22(9):1775–1789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doherty KR, Talbert DR, Trusk PB, Moran DM, Shell SA, Bacus S (2015) Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types. Toxicol Appl Pharmacol 285(1):51–60

    Article  CAS  PubMed  Google Scholar 

  • Du Y, Wang J, Jia J, Song N, Xiang C, Xu J, Hou Z, Su X, Liu B, Jiang T, Zhao D, Sun Y, Shu J, Guo Q, Yin M, Sun D, Lu S, Shi Y, Deng H (2014) Human hepatocytes with drug metabolic function induced from fibroblasts by lineage reprogramming. Cell Stem Cell 14(3):394–403

    Article  CAS  PubMed  Google Scholar 

  • Dubois NC, Craft AM, Sharma P, Elliott DA, Stanley EG, Elefanty AG, Gramolini A, Keller G (2011) SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells. Nat Biotechnol 29(11):1011–1018

    Article  CAS  PubMed  Google Scholar 

  • Ebert AD, Liang P, Wu JC (2012) Induced pluripotent stem cells as a disease modeling and drug screening platform. J Cardiovasc Pharmacol 60(4):408–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujioka Y, Matozaki T, Noguchi T, Iwamatsu A, Yamao T, Takahashi N, Tsuda M, Takada T, Kasuga M (1996) A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion. Mol Cell Biol 16(12):6887–6899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gai H, Leung EL-H, Costantino PD, Aguila JR, Nguyen DM, Fink LM, Ward DC, Ma Y (2009) Generation and characterization of functional cardiomyocytes using induced pluripotent stem cells derived from human fibroblasts. Cell Biol Int 33(11):1184–1193

    Article  CAS  PubMed  Google Scholar 

  • Garbern JC, Lee RT (2013) Cardiac stem cell therapy and the promise of heart regeneration. Cell Stem Cell 12(6):689–698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garbes L, Heesen L, Hölker I, Bauer T, Schreml J, Zimmermann K, Thoenes M, Walter M, Dimos J, Peitz M, Brüstle O, Heller R, Wirth B (2013) VPA response in SMA is suppressed by the fatty acid translocase CD36. Hum Mol Genet 22(2):398–407

    Article  CAS  PubMed  Google Scholar 

  • Ghosh TK, Song FF, Packham EA, Buxton S, Robinson TE, Ronksley J, Self T, Bonser AJ, Brook JD (2009) Physical interaction between TBX5 and MEF2C is required for early heart development. Mol Cell Biol 29(8):2205–2218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ginsberg M, James D, Ding B-S, Nolan D, Geng F, Butler JM, Schachterle W, Pulijaal VR, Mathew S, Chasen ST, Xiang J, Rosenwaks Z, Shido K, Elemento O, Rabbany SY, Rafii S (2012) Efficient direct reprogramming of mature amniotic cells into endothelial cells by ETS factors and TGFβ suppression. Cell 151(3):559–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guha P, Morgan JW, Mostoslavsky G, Rodrigues NP, Boyd AS (2013) Lack of immune response to differentiated cells derived from syngeneic induced pluripotent stem cells. Cell Stem Cell 12(4):407–412

    Article  CAS  PubMed  Google Scholar 

  • Guo Z, Zhang L, Wu Z, Chen Y, Wang F, Chen G (2014) In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model. Cell Stem Cell 14(2):188–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gurdon JB (1962) The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 10(10):622–640

    CAS  PubMed  Google Scholar 

  • Gurdon JB (2013) The egg and the nucleus: a battle for supremacy (Nobel Lecture). Angew Chem Int Ed Engl 52(52):13890–13899

    Article  CAS  PubMed  Google Scholar 

  • Hanna J, Wernig M, Markoulaki S, Sun C-W, Meissner A, Cassady JP, Beard C, Brambrink T, Wu L-C, Townes TM, Jaenisch R (2007) Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318(5858):1920–1923

    Article  CAS  PubMed  Google Scholar 

  • Hasenfuss G (1998) Animal models of human cardiovascular disease, heart failure and hypertrophy. Cardiovasc Res 39(1):60–76

    Article  CAS  PubMed  Google Scholar 

  • Hattori F, Chen H, Yamashita H, Tohyama S, Satoh Y-S, Yuasa S, Li W, Yamakawa H, Tanaka T, Onitsuka T, Shimoji K, Ohno Y, Egashira T, Kaneda R, Murata M, Hidaka K, Morisaki T, Sasaki E, Suzuki T, Sano M, Makino S, Oikawa S, Fukuda K (2010) Nongenetic method for purifying stem cell-derived cardiomyocytes. Nat Methods 7(1):61–66

    Article  CAS  PubMed  Google Scholar 

  • Hausburg F, Na S, Voronina N, Skorska A, Müller P, Steinhoff G, David R (2015) Defining optimized properties of modified mRNA to enhance virus- and DNA- independent protein expression in adult stem cells and fibroblasts. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 35(4):1360–1371

    Article  CAS  Google Scholar 

  • He J-Q, Ma Y, Lee Y, Thomson JA, Kamp TJ (2003) Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ Res 93(1):32–39

    Article  CAS  PubMed  Google Scholar 

  • Heinrich C, Blum R, Gascón S, Masserdotti G, Tripathi P, Sánchez R, Tiedt S, Schroeder T, Götz M, Berninger B (2010) Directing astroglia from the cerebral cortex into subtype specific functional neurons. PLoS Biol 8(5):e1000373

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Heinrich C, Bergami M, Gascón S, Lepier A, Viganò F, Dimou L, Sutor B, Berninger B, Götz M (2014) Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex. Stem Cell Rep 3(6):1000–1014

    Article  CAS  Google Scholar 

  • Heinrich C, Spagnoli FM, Berninger B (2015) In vivo reprogramming for tissue repair. Nat Cell Biol 17(3):204–211

    Article  PubMed  CAS  Google Scholar 

  • Ho S-M, Topol A, Brennand KJ (2015) From \“directed differentiation\” to \“neuronal induction\”: modeling neuropsychiatric disease. Biomark Insights 10(Suppl 1):31–41

    PubMed  PubMed Central  Google Scholar 

  • Hong KU, Li Q-H, Guo Y, Patton NS, Moktar A, Bhatnagar A, Bolli R (2013) A highly sensitive and accurate method to quantify absolute numbers of c-kit + cardiac stem cells following transplantation in mice. Basic Res Cardiol 108(3):346

    Article  PubMed  PubMed Central  Google Scholar 

  • Hosoda T, Zheng H, Cabral-da-Silva M, Sanada F, Ide-Iwata N, Ogórek B, Ferreira-Martins J, Arranto C, D’Amario D, del Monte F, Urbanek K, D’Alessandro DA, Michler RE, Anversa P, Rota M, Kajstura J, Leri A (2011) Human cardiac stem cell differentiation is regulated by a mircrine mechanism. Circulation 123(12):1287–1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, Zhao T, Ye J, Yang W, Liu K, Ge J, Xu J, Zhang Q, Zhao Y, Deng H (2013) Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 341(6146):651–654

    Article  CAS  PubMed  Google Scholar 

  • Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, Hu Y, Wang X, Hui L (2011) Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475(7356):386–389

    Article  CAS  PubMed  Google Scholar 

  • Huang P, Zhang L, Gao Y, He Z, Yao D, Wu Z, Cen J, Chen X, Liu C, Hu Y, Lai D, Hu Z, Chen L, Zhang Y, Cheng X, Ma X, Pan G, Wang X, Hui L (2014) Direct reprogramming of human fibroblasts to functional and expandable hepatocytes. Cell Stem Cell 14(3):370–384

    Article  CAS  PubMed  Google Scholar 

  • Huber I, Itzhaki I, Caspi O, Arbel G, Tzukerman M, Gepstein A, Habib M, Yankelson L, Kehat I, Gepstein L (2007) Identification and selection of cardiomyocytes during human embryonic stem cell differentiation. FASEB J 21(10):2551–2563

    Article  CAS  PubMed  Google Scholar 

  • Hussein SMI, Puri MC, Tonge PD, Benevento M, Corso AJ, Clancy JL, Mosbergen R, Li M, Lee D-S, Cloonan N, Wood DLA, Munoz J, Middleton R, Korn O, Patel HR, White CA, Shin J-Y, Gauthier ME, Lê Cao K-A, Kim J-I, Mar JC, Shakiba N, Ritchie W, Rasko JEJ, Grimmond SM, Zandstra PW, Wells CA, Preiss T, Seo J-S, Heck AJR, Rogers IM, Nagy A (2014) Genome-wide characterization of the routes to pluripotency. Nature 516(7530):198–206

    Article  CAS  PubMed  Google Scholar 

  • Ieda M, Fu J-D, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D (2010) Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142(3):375–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inagawa K, Miyamoto K, Yamakawa H, Muraoka N, Sadahiro T, Umei T, Wada R, Katsumata Y, Kaneda R, Nakade K, Kurihara C, Obata Y, Miyake K, Fukuda K, Ieda M (2012) Induction of cardiomyocyte-like cells in infarct hearts by gene transfer of Gata4, Mef2c, and Tbx5. Circ Res 111(9):1147–1156

    Article  CAS  PubMed  Google Scholar 

  • Inoue H, Nagata N, Kurokawa H, Yamanaka S (2014) iPS cells: a game changer for future medicine. EMBO J 33(5):409–417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Islas JF, Liu Y, Weng K-C, Robertson MJ, Zhang S, Prejusa A, Harger J, Tikhomirova D, Chopra M, Iyer D, Mercola M, Oshima RG, Willerson JT, Potaman VN, Schwartz RJ (2012) Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors. Proc Natl Acad Sci U S A 109(32):13016–13021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itzhaki I, Maizels L, Huber I, Zwi-Dantsis L, Caspi O, Winterstern A, Feldman O, Gepstein A, Arbel G, Hammerman H, Boulos M, Gepstein L (2011) Modelling the long QT syndrome with induced pluripotent stem cells. Nature 471(7337):225–229

    Article  CAS  PubMed  Google Scholar 

  • James D, Nam H-S, Seandel M, Nolan D, Janovitz T, Tomishima M, Studer L, Lee G, Lyden D, Benezra R, Zaninovic N, Rosenwaks Z, Rabbany SY, Rafii S (2010) Expansion and maintenance of human embryonic stem cell-derived endothelial cells by TGFbeta inhibition is Id1 dependent. Nat Biotechnol 28(2):161–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jayawardena TM, Egemnazarov B, Finch EA, Zhang L, Payne JA, Pandya K, Zhang Z, Rosenberg P, Mirotsou M, Dzau VJ (2012) MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res 110(11):1465–1473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jayawardena T, Mirotsou M, Dzau VJ (2014) Direct reprogramming of cardiac fibroblasts to cardiomyocytes using microRNAs. Methods Mol Biol 1150:263–272

    Article  CAS  PubMed  Google Scholar 

  • Jiang B, Xiang Z, Ai Z, Wang H, Li Y, Ji W, Li T (2015) Generation of cardiac spheres from primate pluripotent stem cells in a small molecule-based 3D system. Biomaterials 65:103–114

    Article  CAS  PubMed  Google Scholar 

  • Jung JJ, Husse B, Rimmbach C, Krebs S, Stieber J, Steinhoff G, Dendorfer A, Franz W-M, David R (2014) Programming and isolation of highly pure physiologically and pharmacologically functional sinus-nodal bodies from pluripotent stem cells. Stem Cell Rep 2(5):592–605

    Article  Google Scholar 

  • Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K (2009) Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 458(7239):771–775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamao H, Mandai M, Okamoto S, Sakai N, Suga A, Sugita S, Kiryu J, Takahashi M (2014) Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Rep 2(2):205–218

    Article  CAS  Google Scholar 

  • Kanemura H, Go MJ, Shikamura M, Nishishita N, Sakai N, Kamao H, Mandai M, Morinaga C, Takahashi M, Kawamata S (2014) Tumorigenicity studies of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration. PLoS One 9(1):e85336

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Karakikes I, Ameen M, Termglinchan V, Wu JC (2015) Human induced pluripotent stem cell-derived cardiomyocytes: insights into molecular, cellular, and functional phenotypes. Circ Res 117(1):80–88

    Article  CAS  PubMed  Google Scholar 

  • Karikó K, Muramatsu H, Keller JM, Weissman D (2012) Increased erythropoiesis in mice injected with submicrogram quantities of pseudouridine-containing mRNA encoding erythropoietin. Mol Ther 20(5):948–953

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kattman SJ, Huber TL, Keller GM (2006) Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. Dev Cell 11(5):723–732

    Article  CAS  PubMed  Google Scholar 

  • Kattman SJ, Witty AD, Gagliardi M, Dubois NC, Niapour M, Hotta A, Ellis J, Keller G (2011) Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8(2):228–240

    Article  CAS  PubMed  Google Scholar 

  • Katz TC, Singh MK, Degenhardt K, Rivera-Feliciano J, Johnson RL, Epstein JA, Tabin CJ (2012) Distinct compartments of the proepicardial organ give rise to coronary vascular endothelial cells. Dev Cell 22(3):639–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M, Gepstein A, Livne E, Binah O, Itskovitz-Eldor J, Gepstein L (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 108(3):407–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A (1997) A family of proteins that inhibit signalling through tyrosine kinase receptors. Nature 386(6621):181–186

    Article  CAS  PubMed  Google Scholar 

  • Kim D, Kim C-H, Moon J-I, Chung Y-G, Chang M-Y, Han B-S, Ko S, Yang E, Cha KY, Lanza R, Kim K-S (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4(6):472–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim YJ, Lim H, Li Z, Oh Y, Kovlyagina I, Choi IY, Dong X, Lee G (2014) Generation of multipotent induced neural crest by direct reprogramming of human postnatal fibroblasts with a single transcription factor. Cell Stem Cell 15(4):497–506

    Article  CAS  PubMed  Google Scholar 

  • Kitaoka S, Kondoh H, Inoue H (eds) (2011) Induced pluripotent stem cell technology for the study of neurodegenerative diseases, induced stem cells. Nova Science Publishers Inc, New York

    Google Scholar 

  • Knollmann BC (2013) Induced pluripotent stem cell-derived cardiomyocytes: boutique science or valuable arrhythmia model? Circ Res 112(6):969–976; discussion 976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kondo T, Asai M, Tsukita K, Kutoku Y, Ohsawa Y, Sunada Y, Imamura K, Egawa N, Yahata N, Okita K, Takahashi K, Asaka I, Aoi T, Watanabe A, Watanabe K, Kadoya C, Nakano R, Watanabe D, Maruyama K, Hori O, Hibino S, Choshi T, Nakahata T, Hioki H, Kaneko T, Naitoh M, Yoshikawa K, Yamawaki S, Suzuki S, Hata R, Ueno S-I, Seki T, Kobayashi K, Toda T, Murakami K, Irie K, Klein WL, Mori H, Asada T, Takahashi R, Iwata N, Yamanaka S, Inoue H (2013) Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness. Cell Stem Cell 12(4):487–496

    Article  CAS  PubMed  Google Scholar 

  • Kormann MSD, Hasenpusch G, Aneja MK, Nica G, Flemmer AW, Herber-Jonat S, Huppmann M, Mays LE, Illenyi M, Schams A, Griese M, Bittmann I, Handgretinger R, Hartl D, Rosenecker J, Rudolph C (2011) Expression of therapeutic proteins after delivery of chemically modified mRNA in mice. Nat Biotechnol 29(2):154–157

    Article  CAS  PubMed  Google Scholar 

  • Kraehenbuehl TP, Ferreira LS, Hayward AM, Nahrendorf M, van der Vlies AJ, Vasile E, Weissleder R, Langer R, Hubbell JA (2011) Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction. Biomaterials 32(4):1102–1109

    Article  CAS  PubMed  Google Scholar 

  • Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23(7):845–856

    Article  CAS  PubMed  Google Scholar 

  • Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, Reinecke H, Xu C, Hassanipour M, Police S, O’Sullivan C, Collins L, Chen Y, Minami E, Gill EA, Ueno S, Yuan C, Gold J, Murry CE (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25(9):1015–1024

    Article  CAS  PubMed  Google Scholar 

  • Lan F, Lee AS, Liang P, Sanchez-Freire V, Nguyen PK, Wang L, Han L, Yen M, Wang Y, Sun N, Abilez OJ, Hu S, Ebert AD, Navarrete EG, Simmons CS, Wheeler M, Pruitt B, Lewis R, Yamaguchi Y, Ashley EA, Bers DM, Robbins RC, Longaker MT, Wu JC (2013) Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent stem cells. Cell Stem Cell 12(1):101–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lang C, Lehner S, Todica A, Boening G, Zacherl M, Franz W-M, Krause BJ, Bartenstein P, Hacker M, David R (2014) In-vivo comparison of the acute retention of stem cell derivatives and fibroblasts after intramyocardial transplantation in the mouse model. Eur J Nucl Med Mol Imaging 41(12):2325–2336

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Sayed N, Hunter A, Au KF, Wong WH, Mocarski ES, Pera RR, Yakubov E, Cooke JP (2012) Activation of innate immunity is required for efficient nuclear reprogramming. Cell 151(3):547–558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee D-S, Shin J-Y, Tonge PD, Puri MC, Lee S, Park H, Lee W-C, Hussein SMI, Bleazard T, Yun J-Y, Kim J, Li M, Cloonan N, Wood D, Clancy JL, Mosbergen R, Yi J-H, Yang K-S, Kim H, Rhee H, Wells CA, Preiss T, Grimmond SM, Rogers IM, Nagy A, Seo J-S (2014) An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator. Nat Commun 5:5619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lemper M, Leuckx G, Heremans Y, German MS, Heimberg H, Bouwens L, Baeyens L (2015) Reprogramming of human pancreatic exocrine cells to β-like cells. Cell Death Differ 22(7):1117–1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lensch MW, Schlaeger TM, Zon LI, Daley GQ (2007) Teratoma formation assays with human embryonic stem cells: a rationale for one type of human-animal chimera. Cell Stem Cell 1(3):253–258

    Article  CAS  PubMed  Google Scholar 

  • Lerou PH, Daley GQ (2005) Therapeutic potential of embryonic stem cells. Blood Rev 19(6):321–331

    Article  PubMed  Google Scholar 

  • Lev S, Kehat I, Gepstein L (2005) Differentiation pathways in human embryonic stem cell-derived cardiomyocytes. Ann N Y Acad Sci 1047:50–65

    Article  CAS  PubMed  Google Scholar 

  • Li Y-P, Wang Y (2015) Large noncoding RNAs are promising regulators in embryonic stem cells. J Genet Genom = Yi chuan xue bao 42(3):99–105

    Article  CAS  Google Scholar 

  • Lian X, Hsiao C, Wilson G, Zhu K, Hazeltine LB, Azarin SM, Raval KK, Zhang J, Kamp TJ, Palecek SP (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci U S A 109(27):E1848–E1857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lian X, Zhang J, Azarin SM, Zhu K, Hazeltine LB, Bao X, Hsiao C, Kamp TJ, Palecek SP (2013) Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions. Nat Protoc 8(1):162–175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang P, Lan F, Lee AS, Gong T, Sanchez-Freire V, Wang Y, Diecke S, Sallam K, Knowles JW, Wang PJ, Nguyen PK, Bers DM, Robbins RC, Wu JC (2013a) Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation 127(16):1677–1691

    Article  CAS  PubMed  Google Scholar 

  • Liang X, Wang G, Lin L, Lowe J, Zhang Q, Bu L, Chen Y, Chen J, Sun Y, Evans SM (2013b) HCN4 dynamically marks the first heart field and conduction system precursors. Circ Res 113(4):399–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindvall O, Björklund A (2004) Cell therapy in Parkinson’s disease. NeuroRx 1(4):382–393

    Article  PubMed  PubMed Central  Google Scholar 

  • Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Antosiewicz-Bourget J, O’Malley R, Castanon R, Klugman S, Downes M, Yu R, Stewart R, Ren B, Thomson JA, Evans RM, Ecker JR (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471(7336):68–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Liu Y, Wang H, Hao H, Han Q, Shen J, Shi J, Li C, Mu Y, Han W (2013) Direct differentiation of hepatic stem-like WB cells into insulin-producing cells using small molecules. Sci Rep 3:1185

    PubMed  PubMed Central  Google Scholar 

  • Loffredo FS, Steinhauser ML, Gannon J, Lee RT (2011) Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell 8(4):389–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mah N, Wang Y, Liao M-C, Prigione A, Jozefczuk J, Lichtner B, Wolfrum K, Haltmeier M, Flöttmann M, Schaefer M, Hahn A, Mrowka R, Klipp E, Andrade-Navarro MA, Adjaye J (2011) Molecular insights into reprogramming-initiation events mediated by the OSKM gene regulatory networ. PLoS One 6(8):e24351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maitra M, Schluterman MK, Nichols HA, Richardson JA, Lo CW, Srivastava D, Garg V (2009) Interaction of Gata4 and Gata6 with Tbx5 is critical for normal cardiac development. Dev Biol 326(2):368–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malliaras K, Zhang Y, Seinfeld J, Galang G, Tseliou E, Cheng K, Sun B, Aminzadeh M, Marbán E (2013) Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart. EMBO Mol Med 5(2):191–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mandal PK, Rossi DJ (2013) Reprogramming human fibroblasts to pluripotency using modified mRNA. Nat Protoc 8(3):568–582

    Article  PubMed  CAS  Google Scholar 

  • Matar AA, Chong JJ (2014) Stem cell therapy for cardiac dysfunction. SpringerPlus 3:440

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mauritz C, Martens A, Rojas SV, Schnick T, Rathert C, Schecker N, Menke S, Glage S, Zweigerdt R, Haverich A, Martin U, Kutschka I (2011) Induced pluripotent stem cell (iPSC)-derived Flk-1 progenitor cells engraft, differentiate, and improve heart function in a mouse model of acute myocardial infarction. Eur Heart J 32(21):2634–2641

    Article  CAS  PubMed  Google Scholar 

  • Melkoumian Z, Weber JL, Weber DM, Fadeev AG, Zhou Y, Dolley-Sonneville P, Yang J, Qiu L, Priest CA, Shogbon C, Martin AW, Nelson J, West P, Beltzer JP, Pal S, Brandenberger R (2010) Synthetic peptide-acrylate surfaces for long-term self-renewal and cardiomyocyte differentiation of human embryonic stem cells. Nat Biotechnol 28(6):606–610

    Article  CAS  PubMed  Google Scholar 

  • Misfeldt AM, Boyle SC, Tompkins KL, Bautch VL, Labosky PA, Baldwin HS (2009) Endocardial cells are a distinct endothelial lineage derived from Flk1+ multipotent cardiovascular progenitors. Dev Biol 333(1):78–89

    Article  CAS  PubMed  Google Scholar 

  • Miyoshi N, Ishii H, Nagano H, Haraguchi N, Dewi DL, Kano Y, Nishikawa S, Tanemura M, Mimori K, Tanaka F, Saito T, Nishimura J, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M (2011) Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 8(6):633–638

    Article  CAS  PubMed  Google Scholar 

  • Mollova M, Bersell K, Walsh S, Savla J, Das LT, Park S-Y, Silberstein LE, Remedios D, Cristobal G, Graham D, Colan S, Kühn B (2013) Cardiomyocyte proliferation contributes to heart growth in young humans. Proc Natl Acad Sci U S A 110(4):1446–1451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mordwinkin NM, Burridge PW, Wu JC (2013) A review of human pluripotent stem cell-derived cardiomyocytes for high-throughput drug discovery, cardiotoxicity screening, and publication standards. J Cardiovasc Transl Res 6(1):22–30

    Article  PubMed  PubMed Central  Google Scholar 

  • Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz K-L, Chien KR (2006) Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127(6):1151–1165

    Article  CAS  PubMed  Google Scholar 

  • Moretti A, Bellin M, Welling A, Jung CB, Lam JT, Bott-Flügel L, Dorn T, Goedel A, Höhnke C, Hofmann F, Seyfarth M, Sinnecker D, Schömig A, Laugwitz K-L (2010) Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med 363(15):1397–1409

    Article  CAS  PubMed  Google Scholar 

  • Morita R, Suzuki M, Kasahara H, Shimizu N, Shichita T, Sekiya T, Kimura A, Sasaki AI, Yasukawa H, Yoshimura A (2015) ETS transcription factor ETV2 directly converts human fibroblasts into functional endothelial cells. Proc Natl Acad Sci U S A 112(1):160–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morizane A, Doi D, Kikuchi T, Okita K, Hotta A, Kawasaki T, Hayashi T, Onoe H, Shiina T, Yamanaka S, Takahashi J (2013) Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate. Stem Cell Rep 1(4):283–292

    Article  CAS  Google Scholar 

  • Mothe AJ, Tator CH (2013) Review of transplantation of neural stem/progenitor cells for spinal cord injury. Int J Dev Neurosci 31(7):701–713

    Article  CAS  PubMed  Google Scholar 

  • Musunuru K, Domian IJ, Chien KR (2010) Stem cell models of cardiac development and disease. Annu Rev Cell Dev Biol 26:667–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson TJ, Martinez-Fernandez A, Yamada S, Perez-Terzic C, Ikeda Y, Terzic A (2009) Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation 120(5):408–416

    Article  PubMed  PubMed Central  Google Scholar 

  • Neve A, Corrado A, Cantatore FP (2011) Osteoblast physiology in normal and pathological conditions. Cell Tissue Res 343(2):289–302

    Article  CAS  PubMed  Google Scholar 

  • Nussbaum J, Minami E, Laflamme MA, Virag JAI, Ware CB, Masino A, Muskheli V, Pabon L, Reinecke H, Murry CE (2007) Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response. FASEB J 21(7):1345–1357

    Article  CAS  PubMed  Google Scholar 

  • Olson EN (2006) Gene regulatory networks in the evolution and development of the heart. Science 313(5795):1922–1927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ong S-G, Lee WH, Kodo K, Wu JC (2015) MicroRNA-mediated regulation of differentiation and trans-differentiation in stem cells”. Adv Drug Deliv Rev 88:3–15

    Article  CAS  PubMed  Google Scholar 

  • Otsuji TG, Bin J, Yoshimura A, Tomura M, Tateyama D, Minami I, Yoshikawa Y, Aiba K, Heuser JE, Nishino T, Hasegawa K, Nakatsuji N (2014) A 3D sphere culture system containing functional polymers for large-scale human pluripotent stem cell production. Stem Cell Rep 2(5):734–745

    Article  CAS  Google Scholar 

  • Pavo N, Charwat S, Nyolczas N, Jakab A, Murlasits Z, Bergler-Klein J, Nikfardjam M, Benedek I, Benedek T, Pavo IJ, Gersh BJ, Huber K, Maurer G, Gyöngyösi M (2014) Cell therapy for human ischemic heart diseases: critical review and summary of the clinical experiences. J Mol Cell Cardiol 75:12–24

    Article  CAS  PubMed  Google Scholar 

  • Polo JM, Anderssen E, Walsh RM, Schwarz BA, Nefzger CM, Lim SM, Borkent M, Apostolou E, Alaei S, Cloutier J, Bar-Nur O, Cheloufi S, Stadtfeld M, Figueroa ME, Robinton D, Natesan S, Melnick A, Zhu J, Ramaswamy S, Hochedlinger K (2012) A molecular roadmap of reprogramming somatic cells into iPS cells. Cell 151(7):1617–1632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, Conway SJ, Fu J-D, Srivastava D (2012) In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 485(7400):593–598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian L, Berry EC, Fu J-D, Ieda M, Srivastava D (2013) Reprogramming of mouse fibroblasts into cardiomyocyte-like cells in vitro. Nat Protoc 8(6):1204–1215

    Article  PubMed  CAS  Google Scholar 

  • Quabius ES, Krupp G (2015) Synthetic mRNAs for manipulating cellular phenotypes: an overview. New Biotechnol 32(1):229–235

    Article  CAS  Google Scholar 

  • Reynolds J, Lamba DA (2014) Human embryonic stem cell applications for retinal degenerations. Exp Eye Res 123:151–160

    Article  CAS  PubMed  Google Scholar 

  • Rimmbach C, Jung JJ, David R (2015) Generation of murine cardiac pacemaker cell aggregates based on ES-cell-programming in combination with Myh6-promoter-selection. J Vis Exp 96:e52465

    PubMed  Google Scholar 

  • Rosen MR, Myerburg RJ, Francis DP, Cole GD, Marbán E (2014) Translating stem cell research to cardiac disease therapies: pitfalls and prospects for improvement. J Am Coll Cardiol 64(9):922–937

    Article  PubMed  PubMed Central  Google Scholar 

  • Sahara M, Santoro F, Chien KR (2015) Programming and reprogramming a human heart cell. EMBO J 34(6):710–738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sandler VM, Lis R, Liu Y, Kedem A, James D, Elemento O, Butler JM, Scandura JM, Rafii S (2014) Reprogramming human endothelial cells to haematopoietic cells requires vascular induction. Nature 511(7509):312–318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sayed N, Wong WT, Ospino F, Meng S, Lee J, Jha A, Dexheimer P, Aronow BJ, Cooke JP (2015) Transdifferentiation of human fibroblasts to endothelial cells: role of innate immunity. Circulation 131(3):300–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schlueter J, Brand T (2012) Epicardial progenitor cells in cardiac development and regeneration. J Cardiovasc Transl Res 5(5):641–653

    Article  PubMed  Google Scholar 

  • Schwartz SD, Hubschman J-P, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R (2012) Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379(9817):713–720

    Article  CAS  PubMed  Google Scholar 

  • Schwartz SD, Regillo CD, Lam BL, Eliott D, Rosenfeld PJ, Gregori NZ, Hubschman J-P, Davis JL, Heilwell G, Spirn M, Maguire J, Gay R, Bateman J, Ostrick RM, Morris D, Vincent M, Anglade E, Priore D, Lucian V, Lanza R (2015) Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet 385(9967):509–516

    Article  PubMed  Google Scholar 

  • Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, Wu T-D, Guerquin-Kern J-L, Lechene CP, Lee RT (2013) Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493(7432):433–436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharrocks AD (2001) The ETS-domain transcription factor family. Nat Rev Mol Cell Biol 2(11):827–837

    Article  CAS  PubMed  Google Scholar 

  • Shiba Y, Fernandes S, Zhu W-Z, Filice D, Muskheli V, Kim J, Palpant NJ, Gantz J, Moyes KW, Reinecke H, van Biber B, Dardas T, Mignone JL, Izawa A, Hanna R, Viswanathan M, Gold JD, Kotlikoff MI, Sarvazyan N, Kay MW, Murry CE, Laflamme MA (2012) Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. Nature 489(7415):322–325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Si-Tayeb K, Noto FK, Nagaoka M, Li J, Battle MA, Duris C, North PE, Dalton S, Duncan SA (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51(1):297–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sluijter JPG, van Mil A, van Vliet P, Metz CHG, Liu J, Doevendans PA, Goumans M-J (2010) MicroRNA-1 and −499 regulate differentiation and proliferation in human-derived cardiomyocyte progenitor cells. Arterioscler Thromb Vasc Biol 30(4):859–868

    Article  CAS  PubMed  Google Scholar 

  • Smith DK, Zhang C-L (2015) Regeneration through reprogramming adult cell identity in vivo. Am J Pathol 185(10):2619–2628

    Article  PubMed  Google Scholar 

  • Song K, Nam Y-J, Luo X, Qi X, Tan W, Huang GN, Acharya A, Smith CL, Tallquist MD, Neilson EG, Hill JA, Bassel-Duby R, Olson EN (2012) Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature 485(7400):599–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Später D, Abramczuk MK, Buac K, Zangi L, Stachel MW, Clarke J, Sahara M, Ludwig A, Chien KR (2013) A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells. Nat Cell Biol 15(9):1098–1106

    Article  PubMed  CAS  Google Scholar 

  • Srivastava D (2006) Making or breaking the heart: from lineage determination to morphogenesis. Cell 126(6):1037–1048

    Article  CAS  PubMed  Google Scholar 

  • Sturgeon CM, Ditadi A, Clarke RL, Keller G (2013) Defining the path to hematopoietic stem cells. Nat Biotechnol 31(5):416–418

    Article  CAS  PubMed  Google Scholar 

  • Sullivan GJ, Hay DC, Park I-H, Fletcher J, Hannoun Z, Payne CM, Dalgetty D, Black JR, Ross JA, Samuel K, Wang G, Daley GQ, Lee J-H, Church GM, Forbes SJ, Iredale JP, Wilmut I (2010) Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 51(1):329–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swijnenburg R-J, Sheikh AY, Robbins RC (2007) Comment on \“Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response\”. FASEB J 21(7):1290; author reply 1291

    Google Scholar 

  • Swijnenburg R-J, Schrepfer S, Govaert JA, Cao F, Ransohoff K, Sheikh AY, Haddad M, Connolly AJ, Davis MM, Robbins RC, Wu JC (2008) Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. Proc Natl Acad Sci U S A 105(35):12991–12996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szabo E, Rampalli S, Risueño RM, Schnerch A, Mitchell R, Fiebig-Comyn A, Levadoux-Martin M, Bhatia M (2010) Direct conversion of human fibroblasts to multilineage blood progenitors. Nature 468(7323):521–526

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872

    Article  CAS  PubMed  Google Scholar 

  • Thompson SA, Burridge PW, Lipke EA, Shamblott M, Zambidis ET, Tung L (2012) Engraftment of human embryonic stem cell derived cardiomyocytes improves conduction in an arrhythmogenic in vitro model. J Mol Cell Cardiol 53(1):15–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomson JA (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Tohyama S, Hattori F, Sano M, Hishiki T, Nagahata Y, Matsuura T, Hashimoto H, Suzuki T, Yamashita H, Satoh Y, Egashira T, Seki T, Muraoka N, Yamakawa H, Ohgino Y, Tanaka T, Yoichi M, Yuasa S, Murata M, Suematsu M, Fukuda K (2013) Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell-derived cardiomyocytes. Cell Stem Cell 12(1):127–137

    Article  CAS  PubMed  Google Scholar 

  • Tonge PD, Corso AJ, Monetti C, Hussein SMI, Puri MC, Michael IP, Li M, Lee D-S, Mar JC, Cloonan N, Wood DL, Gauthier ME, Korn O, Clancy JL, Preiss T, Grimmond SM, Shin J-Y, Seo J-S, Wells CA, Rogers IM, Nagy A (2014) Divergent reprogramming routes lead to alternative stem-cell states. Nature 516(7530):192–197

    Article  CAS  PubMed  Google Scholar 

  • Uosaki H, Fukushima H, Takeuchi A, Matsuoka S, Nakatsuji N, Yamanaka S, Yamashita JK (2011) Efficient and scalable purification of cardiomyocytes from human embryonic and induced pluripotent stem cells by VCAM1 surface expression. PLoS One 6(8):e23657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Hoof D, Dormeyer W, Braam SR, Passier R, Monshouwer-Kloots J, Ward-van Oostwaard D, Heck AJR, Krijgsveld J, Mummery CL (2010) Identification of cell surface proteins for antibody-based selection of human embryonic stem cell-derived cardiomyocytes. J Proteome Res 9(3):1610–1618

    Article  PubMed  CAS  Google Scholar 

  • van Laake LW, Qian L, Cheng P, Huang Y, Hsiao EC, Conklin BR, Srivastava D (2010) Reporter-based isolation of induced pluripotent stem cell- and embryonic stem cell-derived cardiac progenitors reveals limited gene expression variance. Circ Res 107(3):340–347

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vian L, Di Carlo M, Pelosi E, Fazi F, Santoro S, Cerio AM, Boe A, Rotilio V, Billi M, Racanicchi S, Testa U, Grignani F, Nervi C (2014) Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of human hematopoietic progenitors. Cell Death Differ 21(2):290–301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vincent SD, Buckingham ME (2010) How to make a heart. In: Koopman P (ed) Organogenesis in development, vol 90, Current topics in developmental biology. Elsevier, Heidelberg, pp 1–41

    Chapter  Google Scholar 

  • Wang Z, Wang D-Z, Pipes GC, Olson EN (2003) Myocardin is a master regulator of smooth muscle gene expression. Proc Natl Acad Sci U S A 100(12):7129–7134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Cao N, Spencer CI, Nie B, Ma T, Xu T, Zhang Y, Wang X, Srivastava D, Ding S (2014) Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, Oct4. Cell Rep 6(5):951–960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang L, Liu Z, Yin C, Asfour H, Chen O, Li Y, Bursac N, Liu J, Qian L (2015) Stoichiometry of Gata4, Mef2c, and Tbx5 influences the efficiency and quality of induced cardiac myocyte reprogramming. Circ Res 116(2):237–244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warren L, Manos PD, Ahfeldt T, Loh Y-H, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7(5):618–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wernig M, Zhao J-P, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R (2008) Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci U S A 105(15):5856–5861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • World Health Organization (2014) WHO methods and data sources for country – level causes of death 2000–2012. Global health estimates technical paper WHO/HIS/HSI/GHE/2014.7. Department of Health Statistics and Information Systems WHO, Geneva

    Google Scholar 

  • Williams BJ, Bhatia S, Adams LK, Boling S, Carroll JL, Li X-L, Rogers DL, Korokhov N, Kovesdi I, Pereboev AV, Curiel DT, Mathis JM (2012) Dendritic cell based PSMA immunotherapy for prostate cancer using a CD40-targeted adenovirus vector. PLoS One 7(10):e46981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385(6619):810–813

    Article  CAS  PubMed  Google Scholar 

  • Xin M, Olson EN, Bassel-Duby R (2013) Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair. Nat Rev Mol Cell Biol 14(8):529–541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu J, Du Y, Deng H (2015) Direct lineage reprogramming: strategies, mechanisms, and applications. Cell Stem Cell 16(2):119–134

    Article  CAS  PubMed  Google Scholar 

  • Yakubov E, Rechavi G, Rozenblatt S, Givol D (2010) Reprogramming of human fibroblasts to pluripotent stem cells using mRNA of four transcription factors. Biochem Biophys Res Commun 394(1):189–193

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto K, Kishida T, Sato Y, Nishioka K, Ejima A, Fujiwara H, Kubo T, Yamamoto T, Kanamura N, Mazda O (2015) Direct conversion of human fibroblasts into functional osteoblasts by defined factors. Proc Natl Acad Sci U S A 112(19):6152–6157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamanaka S (2013) The winding road to pluripotency (Nobel Lecture). Angew Chem Int Ed Engl 52(52):13900–13909

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Soonpaa MH, Adler ED, Roepke TK, Kattman SJ, Kennedy M, Henckaerts E, Bonham K, Abbott GW, Linden RM, Field LJ, Keller GM (2008) Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature 453(7194):524–528

    Article  CAS  PubMed  Google Scholar 

  • Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, Lee-Messer C, Dolmetsch RE, Tsien RW, Crabtree GR (2011) MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476(7359):228–231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920

    Article  CAS  PubMed  Google Scholar 

  • Zangi L, Lui KO, von Gise A, Ma Q, Ebina W, Ptaszek LM, Später D, Xu H, Tabebordbar M, Gorbatov R, Sena B, Nahrendorf M, Briscoe DM, Li RA, Wagers AJ, Rossi DJ, Pu WT, Chien KR (2013) Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction. Nat Biotechnol 31(10):898–907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Wilson GF, Soerens AG, Koonce CH, Yu J, Palecek SP, Thomson JA, Kamp TJ (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res 104(4):e30–e41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao R, Watt AJ, Battle MA, Li J, Bondow BJ, Duncan SA (2008) Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice. Dev Biol 317(2):614–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao T, Zhang Z-N, Rong Z, Xu Y (2011) Immunogenicity of induced pluripotent stem cells. Nature 474(7350):212–215

    Article  CAS  PubMed  Google Scholar 

  • Zhou W, Freed CR (2009) Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells 27(11):2667–2674

    Article  CAS  PubMed  Google Scholar 

  • Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT (2008a) Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454(7200):109–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA (2008b) In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455(7213):627–632

    Article  CAS  PubMed  Google Scholar 

  • Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y, Siuzdak G, Schöler HR, Duan L, Ding S (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4(5):381–384

    Article  CAS  PubMed  Google Scholar 

  • Zhou B, Honor LB, He H, Ma Q, Oh J-H, Butterfield C, Lin R-Z, Melero-Martin JM, Dolmatova E, Duffy HS, von Gise A, Zhou P, Hu YW, Wang G, Zhang B, Wang L, Hall JL, Moses MA, McGowan FX, Pu WT (2011) Adult mouse epicardium modulates myocardial injury by secreting paracrine factors. J Clin Invest 121(5):1894–1904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zwi L, Caspi O, Arbel G, Huber I, Gepstein A, Park I-H, Gepstein L (2009) Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation 120(15):1513–1523

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 68, 18057, Rostock, Germany

    Frauke Hausburg & Robert David

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  1. Frauke Hausburg
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  2. Robert David
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  1. Department of Cardiac Surgery and Refere, University of Rostock, Rostock, Mecklenburg-Vorpomm., Germany

    Gustav Steinhoff

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Hausburg, F., David, R. (2016). Cell Programming for Future Regenerative Medicine. In: Steinhoff, G. (eds) Regenerative Medicine - from Protocol to Patient. Springer, Cham. https://doi.org/10.1007/978-3-319-27610-6_15

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