Abstract
The field of regenerative medicine is looking for a pluripotent/multipotent stem cell able to differentiate across germ layers and be safely employed in therapy. Unfortunately, with the exception of hematopoietic stem/progenitor cells (HSPCs) for hematological applications, the current clinical results with stem cells are somewhat disappointing. The potential clinical applications of the more primitive embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have so far been discouraging, as both have exhibited several problems, including genomic instability, a risk of teratoma formation, and the possibility of rejection. Therefore, the only safe stem cells that have so far been employed in regenerative medicine are monopotent stem cells, such as the abovementioned HSPCs or mesenchymal stem cells (MSCs) isolated from postnatal tissues. However, their monopotency, and therefore limited differentiation potential, is a barrier to their broader application in the clinic. Interestingly, results have accumulated indicating that adult tissues contain rare, early-development stem cells known as very small embryonic-like stem cells (VSELs), which can differentiate into cells from more than one germ layer. This chapter addresses different sources of stem cells for potential clinical application and their advantages and problems to be solved.
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References
Ratajczak MZ, Bujko K, Wojakowski W (2016) Stem cells and clinical practice: new advances and challenges at the time of emerging problems with induced pluripotent stem cell therapies. Pol Arch Med Wewn 126:879–890
Mitalipov S, Wolf D (2009) Totipotency, pluripotency and nuclear reprogramming. Adv Biochem Eng Biotechnol 114:185–199
Condic ML (2014) Totipotency: what it is and what it is not. Stem Cells Dev 23:796–812
Tarkowski AK (1959) Experiments on the development of isolated blastomeres of mouse eggs. Nature 184:1286–1287
Ratajczak MZ, Zuba-Surma E, Kucia M et al (2012) Pluripotent and multipotent stem cells in adult tissues. Adv Med Sci 57:1–17
Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156
Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634–7638
Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147
Ratajczak MZ (2008) Phenotypic and functional characterization of hematopoietic stem cells. Curr Opin Hematol 15:293–300
Ratajczak MZ, Ratajczak J, Suszynska M et al (2017) A novel view of the adult stem cell compartment from the perspective of a quiescent population of very small embryonic-like stem cells. Circ Res 120:166–178
Visvader JE, Clevers H (2016) Tissue-specific designs of stem cell hierarchies. Nat Cell Biol 18:349–355
Li L, Clevers H (2010) Coexistence of quiescent and active adult stem cells in mammals. Science 327:542–545
Kucia M, Reca R, Campbell FR et al (2006) A population of very small embryonic-like (vsel) cxcr4(+)ssea-1(+)oct-4+ stem cells identified in adult bone marrow. Leukemia 20:857–869
Sambasivan R, Tajbakhsh S (2007) Skeletal muscle stem cell birth and properties. Semin Cell Dev Biol 18:870–882
Zummo G, Bucchieri F, Cappello F et al (2007) Adult stem cells: the real root into the embryo? Eur J Histochem 51(Suppl 1):101–103
Morrison SJ, Kimble J (2006) Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 441:1068–1074
Knoblich JA (2008) Mechanisms of asymmetric stem cell division. Cell 132:583–597
Kucia M, Shin DM, Liu R et al (2011) Reduced number of vsels in the bone marrow of growth hormone transgenic mice indicates that chronically elevated igf1 level accelerates age-dependent exhaustion of pluripotent stem cell pool: a novel view on aging. Leukemia 25:1370–1374
Sharples AP, Hughes DC, Deane CS et al (2015) Longevity and skeletal muscle mass: the role of igf signalling, the sirtuins, dietary restriction and protein intake. Aging Cell 14:511–523
Barbera M, di Pietro M, Walker E et al (2015) The human squamous oesophagus has widespread capacity for clonal expansion from cells at diverse stages of differentiation. Gut 64:11–19
DeWard AD, Cramer J, Lagasse E (2014) Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep 9:701–711
Hsu YC, Li L, Fuchs E (2014) Emerging interactions between skin stem cells and their niches. Nat Med 20:847–856
Mahla RS (2016) Stem cells applications in regenerative medicine and disease therapeutics. Int J Cell Biol 2016:6940283
Steindler DA (2007) Stem cells, regenerative medicine, and animal models of disease. ILAR J 48:323–338
Wu LJ, Chen ZY, Wang Y et al (2019) Organoids of liver diseases: from bench to bedside. World J Gastroenterol 25:1913–1927
de Miguel MP, Prieto I, Moratilla A et al (2019) Mesenchymal stem cells for liver regeneration in liver failure: from experimental models to clinical trials. Stem Cells Int 2019:3945672
Orlic D, Kajstura J, Chimenti S et al (2003) Bone marrow stem cells regenerate infarcted myocardium. Pediatr Transplant 7 Suppl 3:86–88
Hofmann M, Wollert KC, Meyer GP et al (2005) Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 111:2198–2202
Lodi D, Iannitti T, Palmieri B (2011) Stem cells in clinical practice: applications and warnings. J Exp Clin Cancer Res 30:9
D’Addio F, Valderrama Vasquez A, Ben Nasr M et al (2014) Autologous nonmyeloablative hematopoietic stem cell transplantation in new-onset type 1 diabetes: a multicenter analysis. Diabetes 63:3041–3046
Radaelli M, Merlini A, Greco R et al (2014) Autologous bone marrow transplantation for the treatment of multiple sclerosis. Curr Neurol Neurosci Rep 14:478
Trounson A, McDonald C (2015) Stem cell therapies in clinical trials: Progress and challenges. Cell Stem Cell 17:11–22
Baraniak PR, McDevitt TC (2010) Stem cell paracrine actions and tissue regeneration. Regen Med 5:121–143
Ratajczak MZ, Ratajczak J (2017) Extracellular microvesicles as game changers in better understanding the complexity of cellular interactions-from bench to clinical applications. Am J Med Sci 354:449–452
Silva TP, Cotovio JP, Bekman E et al (2019) Design principles for pluripotent stem cell-derived organoid engineering. Stem Cells Int 2019:4508470
Liu S, Zhou J, Zhang X et al (2016) Strategies to optimize adult stem cell therapy for tissue regeneration. Int J Mol Sci 17
Kuci S, Kuci Z, Latifi-Pupovci H et al (2009) Adult stem cells as an alternative source of multipotential (pluripotential) cells in regenerative medicine. Curr Stem Cell Res Ther 4:107–117
Holan V, Hermankova B, Bohacova P et al (2016) Distinct immunoregulatory mechanisms in mesenchymal stem cells: role of the cytokine environment. Stem Cell Rev 12:654–663
Ratajczak MZ, Kucia M, Jadczyk T et al (2012) Pivotal role of paracrine effects in stem cell therapies in regenerative medicine: can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies? Leukemia 26:1166–1173
Gatti S, Bruno S, Deregibus MC et al (2011) Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dial Transplant 26:1474–1483
Tapia N, Scholer HR (2016) Molecular obstacles to clinical translation of ipscs. Cell Stem Cell 19:298–309
Walia B, Satija N, Tripathi RP et al (2012) Induced pluripotent stem cells: fundamentals and applications of the reprogramming process and its ramifications on regenerative medicine. Stem Cell Rev 8:100–115
Garber K (2015) Riken suspends first clinical trial involving induced pluripotent stem cells. Nat Biotechnol 33:890–891
Lo B, Parham L (2009) Ethical issues in stem cell research. Endocr Rev 30:204–213
Dresser R (2010) Stem cell research as innovation: expanding the ethical and policy conversation. J Law Med Ethics 38:332–341
Brown C (2012) Stem cell tourism poses risks. CMAJ 184:E121–E122
Master Z, Resnik DB (2011) Stem-cell tourism and scientific responsibility. Stem-cell researchers are in a unique position to curb the problem of stem-cell tourism. EMBO Rep 12:992–995
De Paepe C, Krivega M, Cauffman G et al (2014) Totipotency and lineage segregation in the human embryo. Mol Hum Reprod 20:599–618
Morgani SM, Brickman JM (2014) The molecular underpinnings of totipotency. Philos Trans R Soc Lond Ser B Biol Sci 369:20130549
Qin Y, Qin J, Zhou C et al (2015) Generation of embryonic stem cells from mouse adipose-tissue derived cells via somatic cell nuclear transfer. Cell Cycle 14:1282–1290
Tachibana M, Amato P, Sparman M et al (2013) Human embryonic stem cells derived by somatic cell nuclear transfer. Cell 153:1228–1238
Brons IG, Smithers LE, Trotter MW et al (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448:191–195
Anversa P, Rota M, Urbanek K et al (2005) Myocardial aging – a stem cell problem. Basic Res Cardiol 100:482–493
Ratajczak MZ, Zuba-Surma EK, Wysoczynski M et al (2008) Hunt for pluripotent stem cell – regenerative medicine search for almighty cell. J Autoimmun 30:151–162
Beltrami AP, Cesselli D, Bergamin N et al (2007) Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow). Blood 110:3438–3446
Kuroda Y, Wakao S, Kitada M et al (2013) Isolation, culture and evaluation of multilineage-differentiating stress-enduring (muse) cells. Nat Protoc 8:1391–1415
Jiang Y, Jahagirdar BN, Reinhardt RL et al (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49
Jiang Y, Vaessen B, Lenvik T et al (2002) Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol 30:896–904
Kogler G, Sensken S, Airey JA et al (2004) A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 200:123–135
D’Ippolito G, Diabira S, Howard GA et al (2004) Marrow-isolated adult multilineage inducible (Miami) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J Cell Sci 117:2971–2981
Cesselli D, Beltrami AP, Rigo S et al (2009) Multipotent progenitor cells are present in human peripheral blood. Circ Res 104:1225–1234
Gordon MY (2008) Stem cells for regenerative medicine – biological attributes and clinical application. Exp Hematol 36:726–732
Vacanti MP, Roy A, Cortiella J et al (2001) Identification and initial characterization of spore-like cells in adult mammals. J Cell Biochem 80:455–460
Orlic D, Anderson S, Bodine DM (1994) Biological properties of subpopulations of pluripotent hematopoietic stem cells enriched by elutriation and flow cytometry. Blood Cells 20:107–117; discussion 118–120
Jones RJ, Wagner JE, Celano P et al (1990) Separation of pluripotent haematopoietic stem cells from spleen colony-forming cells. Nature 347:188–189
Krause DS, Theise ND, Collector MI et al (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105:369–377
Shaikh A, Anand S, Kapoor S et al (2017) Mouse bone marrow vsels exhibit differentiation into three embryonic germ lineages and germ & hematopoietic cells in culture. Stem Cell Rev 13:202–216
Shin DM, Liu R, Klich I et al (2010) Molecular characterization of isolated from murine adult tissues very small embryonic/epiblast like stem cells (vsels). Mol Cells 29:533–538
Lahlil R, Scrofani M, Barbet R et al (2018) Vsels maintain their pluripotency and competence to differentiate after enhanced ex vivo expansion. Stem Cell Rev 14:510–524
Bhartiya D (2019) Clinical translation of stem cells for regenerative medicine. Circ Res 124:840–842
Ratajczak MZ, Ratajczak J, Kucia M (2019) Very small embryonic-like stem cells (vsels). Circ Res 124:208–210
Ratajczak MZ (2018) Mulhouse strategy to expand ex vivo very small embryonic like stem cells (vsels) – recent study published in stem cell reviews and reports. Stem Cell Rev 14:461–462
Guerin CL, Loyer X, Vilar J et al (2015) Bone-marrow-derived very small embryonic-like stem cells in patients with critical leg ischaemia: evidence of vasculogenic potential. Thromb Haemost 113:1084–1094
Guerin CL, Rossi E, Saubamea B et al (2017) Human very small embryonic-like cells support vascular maturation and therapeutic revascularization induced by endothelial progenitor cells. Stem Cell Rev 13:552–560
Ratajczak MZ, Shin DM, Liu R et al (2012) Very small embryonic/epiblast-like stem cells (vsels) and their potential role in aging and organ rejuvenation – an update and comparison to other primitive small stem cells isolated from adult tissues. Aging 4:235–246
Shin DM, Zuba-Surma EK, Wu W et al (2009) Novel epigenetic mechanisms that control pluripotency and quiescence of adult bone marrow-derived oct4(+) very small embryonic-like stem cells. Leukemia 23:2042–2051
Chen ZH, Lv X, Dai H et al (2015) Hepatic regenerative potential of mouse bone marrow very small embryonic-like stem cells. J Cell Physiol 230:1852–1861
Maj M, Schneider G, Ratajczak J et al (2015) The cell cycle- and insulin-signaling-inhibiting mirna expression pattern of very small embryonic-like stem cells contributes to their quiescent state. Exp Biol Med (Maywood) 240:1107–1111
Ratajczak J, Zuba-Surma E, Paczkowska E et al (2011) Stem cells for neural regeneration--a potential application of very small embryonic-like stem cells. J Physiol Pharmacol 62:3–12
Bhartiya D (2017) Shifting gears from embryonic to very small embryonic-like stem cells for regenerative medicine. Indian J Med Res 146:15–21
Bhartiya D (2017) Pluripotent stem cells in adult tissues: struggling to be acknowledged over two decades. Stem Cell Rev 13:713–724
Kucia M, Ratajczak J, Ratajczak MZ (2005) Bone marrow as a source of circulating cxcr4+ tissue-committed stem cells. Biol Cell 97:133–146
Chen C, Fingerhut JM, Yamashita YM (2016) The ins(ide) and outs(ide) of asymmetric stem cell division. Curr Opin Cell Biol 43:1–6
Giebel B (2008) Cell polarity and asymmetric cell division within human hematopoietic stem and progenitor cells. Cells Tissues Organs 188:116–126
Li JJ, Hosseini-Beheshti E, Grau GE, et al (2019) Stem cell-derived extracellular vesicles for treating joint injury and osteoarthritis. Nano 9
Kim S, Kim TM (2019) Generation of mesenchymal stem-like cells for producing extracellular vesicles. World J Stem Cells 11:270–280
Cerletti M, Jang YC, Finley LW et al (2012) Short-term calorie restriction enhances skeletal muscle stem cell function. Cell Stem Cell 10:515–519
Hegab AE, Ozaki M, Meligy FY et al (2019) Calorie restriction enhances adult mouse lung stem cells function and reverses several ageing-induced changes. J Tissue Eng Regen Med 13:295–308
Maredziak M, Smieszek A, Chrzastek K et al (2015) Physical activity increases the total number of bone-marrow-derived mesenchymal stem cells, enhances their osteogenic potential, and inhibits their adipogenic properties. Stem Cells Int 2015:379093
Onoyama S, Qiu L, Low HP et al (2016) Prenatal maternal physical activity and stem cells in umbilical cord blood. Med Sci Sports Exerc 48:82–89
Chen T, Shen L, Yu J et al (2011) Rapamycin and other longevity-promoting compounds enhance the generation of mouse induced pluripotent stem cells. Aging Cell 10:908–911
Zhang S, Jia Z, Ge J et al (2005) Purified human bone marrow multipotent mesenchymal stem cells regenerate infarcted myocardium in experimental rats. Cell Transplant 14:787–798
Gnecchi M, He H, Liang OD et al (2005) Paracrine action accounts for marked protection of ischemic heart by akt-modified mesenchymal stem cells. Nat Med 11:367–368
Khubutiya MS, Vagabov AV, Temnov AA et al (2014) Paracrine mechanisms of proliferative, anti-apoptotic and anti-inflammatory effects of mesenchymal stromal cells in models of acute organ injury. Cytotherapy 16:579–585
Biancone L, Bruno S, Deregibus MC et al (2012) Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol Dial Transplant 27:3037–3042
Giebel B, Kordelas L, Borger V (2017) Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles. Stem Cell Investig 4:84
Al-Nbaheen M, Vishnubalaji R, Ali D et al (2013) Human stromal (mesenchymal) stem cells from bone marrow, adipose tissue and skin exhibit differences in molecular phenotype and differentiation potential. Stem Cell Rev 9:32–43
Samsonraj RM, Raghunath M, Hui JH et al (2013) Telomere length analysis of human mesenchymal stem cells by quantitative pcr. Gene 519:348–355
Trivanovic D, Jaukovic A, Popovic B et al (2015) Mesenchymal stem cells of different origin: comparative evaluation of proliferative capacity, telomere length and pluripotency marker expression. Life Sci 141:61–73
Cai J, Miao X, Li Y et al (2014) Whole-genome sequencing identifies genetic variances in culture-expanded human mesenchymal stem cells. Stem Cell Reports 3:227–233
Mushahary D, Spittler A, Kasper C et al (2018) Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 93:19–31
Borger V, Bremer M, Ferrer-Tur R et al (2017) Mesenchymal stem/stromal cell-derived extracellular vesicles and their potential as novel immunomodulatory therapeutic agents. Int J Mol Sci 18
Angelos MG, Kaufman DS (2015) Pluripotent stem cell applications for regenerative medicine. Curr Opin Organ Transplant 20:663–670
Reik W, Surani MA (2015) Germline and pluripotent stem cells. Cold Spring Harb Perspect Biol 7
Carpenter MK, Rao MS (2015) Concise review: making and using clinically compliant pluripotent stem cell lines. Stem Cells Transl Med 4:381–388
McHugh PR (2004) Zygote and “clonote” – the ethical use of embryonic stem cells. N Engl J Med 351:209–211
Landry DW, Zucker HA (2004) Embryonic death and the creation of human embryonic stem cells. J Clin Invest 114:1184–1186
English K, Wood KJ (2011) Immunogenicity of embryonic stem cell-derived progenitors after transplantation. Curr Opin Organ Transplant 16:90–95
Thompson HL, Manilay JO (2011) Embryonic stem cell-derived hematopoietic stem cells: challenges in development, differentiation, and immunogenicity. Curr Top Med Chem 11:1621–1637
Storchova Z (2016) Too much to differentiate: aneuploidy promotes proliferation and teratoma formation in embryonic stem cells. EMBO J 35:2265–2267
Stachelscheid H, Wulf-Goldenberg A, Eckert K et al (2013) Teratoma formation of human embryonic stem cells in three-dimensional perfusion culture bioreactors. J Tissue Eng Regen Med 7:729–741
Stojkovic M, Stojkovic P, Leary C et al (2005) Derivation of a human blastocyst after heterologous nuclear transfer to donated oocytes. Reprod Biomed Online 11:226–231
Harris J (1997) “Goodbye dolly?” the ethics of human cloning. J Med Ethics 23:353–360
Wernig M, Meissner A, Foreman R et al (2007) In vitro reprogramming of fibroblasts into a pluripotent es-cell-like state. Nature 448:318–324
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676
Villa-Diaz LG, Ross AM, Lahann J et al (2013) Concise review: the evolution of human pluripotent stem cell culture: from feeder cells to synthetic coatings. Stem Cells 31:1–7
Attwood SW, Edel MJ (2019) Ips-cell technology and the problem of genetic instability-can it ever be safe for clinical use? J Clin Med 8
Kanemura H, Go MJ, Shikamura M et al (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:e85336
Yoshihara M, Hayashizaki Y, Murakawa Y (2017) Genomic instability of ipscs: challenges towards their clinical applications. Stem Cell Rev 13:7–16
Ben-David U, Arad G, Weissbein U et al (2014) Aneuploidy induces profound changes in gene expression, proliferation and tumorigenicity of human pluripotent stem cells. Nat Commun 5:4825
Sugiura M, Kasama Y, Araki R et al (2014) Induced pluripotent stem cell generation-associated point mutations arise during the initial stages of the conversion of these cells. Stem Cell Reports 2:52–63
Chin MH, Mason MJ, Xie W et al (2009) Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5:111–123
Baum C (2007) Insertional mutagenesis in gene therapy and stem cell biology. Curr Opin Hematol 14:337–342
Wissing S, Munoz-Lopez M, Macia A et al (2012) Reprogramming somatic cells into ips cells activates line-1 retroelement mobility. Hum Mol Genet 21:208–218
Zhao T, Zhang ZN, Rong Z et al (2011) Immunogenicity of induced pluripotent stem cells. Nature 474:212–215
Buganim Y, Markoulaki S, van Wietmarschen N et al (2014) The developmental potential of ipscs is greatly influenced by reprogramming factor selection. Cell Stem Cell 15:295–309
Mills JA, Wang K, Paluru P et al (2013) Clonal genetic and hematopoietic heterogeneity among human-induced pluripotent stem cell lines. Blood 122:2047–2051
Liang G, Zhang Y (2013) Genetic and epigenetic variations in ipscs: potential causes and implications for application. Cell Stem Cell 13:149–159
Wahlster L, Daley GQ (2016) Progress towards generation of human haematopoietic stem cells. Nat Cell Biol 18:1111–1117
Ban H, Nishishita N, Fusaki N et al (2011) Efficient generation of transgene-free human induced pluripotent stem cells (ipscs) by temperature-sensitive Sendai virus vectors. Proc Natl Acad Sci U S A 108:14234–14239
Miere C, Devito L, Ilic D (2016) Sendai virus-based reprogramming of mesenchymal stromal/stem cells from umbilical cord wharton’s jelly into induced pluripotent stem cells. Methods Mol Biol 1357:33–44
Manzini S, Viiri LE, Marttila S et al (2015) A comparative view on easy to deploy non-integrating methods for patient-specific ipsc production. Stem Cell Rev 11:900–908
Nishimura K, Sano M, Ohtaka M et al (2011) Development of defective and persistent Sendai virus vector: a unique gene delivery/expression system ideal for cell reprogramming. J Biol Chem 286:4760–4771
Miyoshi N, Ishii H, Nagano H et al (2011) Reprogramming of mouse and human cells to pluripotency using mature micrornas. Cell Stem Cell 8:633–638
Liu J, Verma PJ (2015) Synthetic mrna reprogramming of human fibroblast cells. Methods Mol Biol 1330:17–28
Dang J, Rana TM (2016) Enhancing induced pluripotent stem cell generation by microrna. Methods Mol Biol 1357:71–84
Warren L, Manos PD, Ahfeldt T et al (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mrna. Cell Stem Cell 7:618–630
Zhou H, Wu S, Joo JY et al (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4:381–384
Kim D, Kim CH, Moon JI et al (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476
Qin H, Zhao A, Zhang C et al (2016) Epigenetic control of reprogramming and transdifferentiation by histone modifications. Stem Cell Rev 12:708–720
Ando M, Nishimura T, Yamazaki S et al (2015) A safeguard system for induced pluripotent stem cell-derived rejuvenated t cell therapy. Stem Cell Reports 5:597–608
Schuldiner M, Itskovitz-Eldor J, Benvenisty N (2003) Selective ablation of human embryonic stem cells expressing a “suicide” gene. Stem Cells 21:257–265
Polo JM, Liu S, Figueroa ME et al (2010) Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 28:848–855
Malik N, Rao MS (2013) A review of the methods for human ipsc derivation. Methods Mol Biol 997:23–33
Laurent LC, Ulitsky I, Slavin I et al (2011) Dynamic changes in the copy number of pluripotency and cell proliferation genes in human escs and ipscs during reprogramming and time in culture. Cell Stem Cell 8:106–118
Zuba-Surma EK, Kucia M, Abdel-Latif A et al (2008) Morphological characterization of very small embryonic-like stem cells (vsels) by imagestream system analysis. J Cell Mol Med 12:292–303
Ratajczak MZ, Marycz K, Poniewierska-Baran A et al (2014) Very small embryonic-like stem cells as a novel developmental concept and the hierarchy of the stem cell compartment. Adv Med Sci 59:273–280
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Suman, S., Domingues, A., Ratajczak, J., Ratajczak, M.Z. (2019). Potential Clinical Applications of Stem Cells in Regenerative Medicine. In: Ratajczak, M. (eds) Stem Cells. Advances in Experimental Medicine and Biology, vol 1201. Springer, Cham. https://doi.org/10.1007/978-3-030-31206-0_1
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