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Pluripotent Stem Cells and Skeletal Regeneration—Promise and Potential

  • Skeletal Development (E Schipani and E Zelzer, Section Editors)
  • Published:
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Abstract

The bone is a regenerative tissue, capable of healing itself after fractures. However, some circumstances such as critical-size defects, malformations, and tumor destruction may exceed the skeleton’s capacity for self-repair. In addition, bone mass and strength decline with age, leading to an increase in fragility fractures. Therefore, the ability to generate large numbers of patient-specific osteoblasts would have enormous clinical implications for the treatment of skeletal defects and diseases. This review will highlight recent advances in the derivation of pluripotent stem cells, and in their directed differentiation towards bone-forming osteoblasts.

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References

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  1. Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells. 2001;19(3):180–92.

    Article  CAS  PubMed  Google Scholar 

  2. Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol. 1976;4(5):267–74.

    CAS  PubMed  Google Scholar 

  3. Panaroni C, Tzeng YS, Saeed H, Wu JY. Mesenchymal progenitors and the osteoblast lineage in bone marrow hematopoietic niches. Curr Osteoporos Rep. 2014;12(1):22–32.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–7.

    Article  CAS  PubMed  Google Scholar 

  5. Buttery LD, Bourne S, Xynos JD, Wood H, Hughes FJ, Hughes SP, et al. Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells. Tissue Eng. 2001;7(1):89–99.

    Article  CAS  PubMed  Google Scholar 

  6. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292(5819):154–6.

    Article  CAS  PubMed  Google Scholar 

  7. Martin GR. 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. 1981;78(12):7634–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145–7.

    Article  CAS  PubMed  Google Scholar 

  9. Yamanaka S. A fresh look at iPS cells. Cell. 2009;137(1):13–7.

    Article  CAS  PubMed  Google Scholar 

  10. Murry CE, Keller G. Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell. 2008;132(4):661–80.

    Article  CAS  PubMed  Google Scholar 

  11. Carpenter MK, Inokuma MS, Denham J, Mujtaba T, Chiu CP, Rao MS. Enrichment of neurons and neural precursors from human embryonic stem cells. Exp Neurol. 2001;172(2):383–97.

    Article  CAS  PubMed  Google Scholar 

  12. Schuldiner M, Eiges R, Eden A, Yanuka O, Itskovitz-Eldor J, Goldstein RS, et al. Induced neuronal differentiation of human embryonic stem cells. Brain Res. 2001;913(2):201–5.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang SC, Wernig M, Duncan ID, Brustle O, Thomson JA. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol. 2001;19(12):1129–33.

    Article  CAS  PubMed  Google Scholar 

  14. Kehat I, Gepstein A, Spira A, Itskovitz-Eldor J, Gepstein L. High-resolution electrophysiological assessment of human embryonic stem cell-derived cardiomyocytes: a novel in vitro model for the study of conduction. Circ Res. 2002;91(8):659–61.

    Article  CAS  PubMed  Google Scholar 

  15. Xu C, Police S, Rao N, Carpenter MK. Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res. 2002;91(6):501–8.

    Article  CAS  PubMed  Google Scholar 

  16. Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki KL, Tzukerman M. Insulin production by human embryonic stem cells. Diabetes. 2001;50(8):1691–7.

    Article  CAS  PubMed  Google Scholar 

  17. Phillips BW, Belmonte N, Vernochet C, Ailhaud G, Dani C. Compactin enhances osteogenesis in murine embryonic stem cells. Biochem Biophys Res Commun. 2001;284(2):478–84.

    Article  CAS  PubMed  Google Scholar 

  18. Sottile V, Thomson A, McWhir J. In vitro osteogenic differentiation of human ES cells. Cloning Stem Cells. 2003;5(2):149–55.

    Article  CAS  PubMed  Google Scholar 

  19. Bielby RC, Boccaccini AR, Polak JM, Buttery LD. In vitro differentiation and in vivo mineralization of osteogenic cells derived from human embryonic stem cells. Tissue Eng. 2004;10(9–10):1518–25.

    Article  CAS  PubMed  Google Scholar 

  20. Bourne S, Polak JM, Hughes SP, Buttery LD. Osteogenic differentiation of mouse embryonic stem cells: differential gene expression analysis by cDNA microarray and purification of osteoblasts by cadherin-11 magnetically activated cell sorting. Tissue Eng. 2004;10(5–6):796–806.

    Article  CAS  PubMed  Google Scholar 

  21. Camargos BM, Tavares RL, Del Puerto HL, Andrade LO, Camargos AF, Reis FM. BMP-4 increases activin A gene expression during osteogenic differentiation of mouse embryonic stem cells. Growth Factors. 2015;33(2):133–8.

    Article  CAS  PubMed  Google Scholar 

  22. Zur Nieden NI, Kempka G, Ahr HJ. In vitro differentiation of embryonic stem cells into mineralized osteoblasts. Differentiation. 2003;71(1):18–27.

    Article  CAS  PubMed  Google Scholar 

  23. Zur Nieden NI, Price FD, Davis LA, Everitt RE, Rancourt DE. Gene profiling on mixed embryonic stem cell populations reveals a biphasic role for beta-catenin in osteogenic differentiation. Mol Endocrinol. 2007;21(3):674–85.

    Article  CAS  PubMed  Google Scholar 

  24. Xin X, Jiang X, Wang L, Stover ML, Zhan S, Huang J, et al. A site-specific integrated Col2.3GFP reporter identifies osteoblasts within mineralized tissue formed in vivo by human embryonic stem cells. Stem Cells Transl Med. 2014;3(10):1125–37.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Jukes JM, Both SK, Leusink A, Sterk LM, van Blitterswijk CA, de Boer J. Endochondral bone tissue engineering using embryonic stem cells. Proc Natl Acad Sci U S A. 2008;105(19):6840–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Evans ND, Gentleman E, Chen X, Roberts CJ, Polak JM, Stevens MM. Extracellular matrix-mediated osteogenic differentiation of murine embryonic stem cells. Biomaterials. 2010;31(12):3244–52.

    Article  CAS  PubMed  Google Scholar 

  27. Marolt D, Campos IM, Bhumiratana S, Koren A, Petridis P, Zhang G, et al. Engineering bone tissue from human embryonic stem cells. Proc Natl Acad Sci U S A. 2012;109(22):8705–9. This article reported the use of tissue engineering techniques to promote bone formation from ES cells.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Rutledge K, Cheng Q, Pryzhkova M, Harris GM, Jabbarzadeh E. Enhanced differentiation of human embryonic stem cells on extracellular matrix-containing osteomimetic scaffolds for bone tissue engineering. Tissue Eng Part C Methods. 2014;20(11):865–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Alfred R, Taiani JT, Krawetz RJ, Yamashita A, Rancourt DE, Kallos MS. Large-scale production of murine embryonic stem cell-derived osteoblasts and chondrocytes on microcarriers in serum-free media. Biomaterials. 2011;32(26):6006–16.

    CAS  PubMed  Google Scholar 

  30. Taiani JT, Krawetz RJ, Yamashita A, Pauchard Y, Buie HR, Ponjevic D, et al. Embryonic stem cells incorporate into newly formed bone and do not form tumors in an immunocompetent mouse fracture model. Cell Transplant. 2013;22(8):1453–62.

    Article  PubMed  Google Scholar 

  31. Kuznetsov SA, Cherman N, Robey PG. In vivo bone formation by progeny of human embryonic stem cells. Stem Cells Dev. 2011;20(2):269–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Ehnes DD, Price FD, Shrive NG, Hart DA, Rancourt DE, Zur Nieden NI. Embryonic stem cell-derived osteocytes are capable of responding to mechanical oscillatory hydrostatic pressure. J Biomech. 2015;48(10):1915–21.

    Article  CAS  PubMed  Google Scholar 

  33. Li M, Li X, Meikle MC, Islam I, Cao T. Short periods of cyclic mechanical strain enhance triple-supplement directed osteogenesis and bone nodule formation by human embryonic stem cells in vitro. Tissue Eng Part A. 2013;19(19–20):2130–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Kim K, Zhao R, Doi A, Ng K, Unternaehrer J, Cahan P, et al. Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat Biotechnol. 2011;29(12):1117–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    Article  CAS  PubMed  Google Scholar 

  36. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20.

    Article  CAS  PubMed  Google Scholar 

  37. Illich DJ, Demir N, Stojkovic M, Scheer M, Rothamel D, Neugebauer J, et al. Concise review: induced pluripotent stem cells and lineage reprogramming: prospects for bone regeneration. Stem Cells. 2011;29(4):555–63.

    Article  CAS  PubMed  Google Scholar 

  38. Yamanaka S. Induced pluripotent stem cells: past, present, and future. Cell Stem Cell. 2012;10(6):678–84. This review, authored by the discoverer of iPS cells, summarizes the history and potential applications of iPSC technology.

    Article  CAS  PubMed  Google Scholar 

  39. Schlaeger TM, Daheron L, Brickler TR, Entwisle S, Chan K, Cianci A, et al. A comparison of non-integrating reprogramming methods. Nat Biotechnol. 2015;33(1):58–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, et al. A more efficient method to generate integration-free human iPS cells. Nat Methods. 2011;8(5):409–12.

    Article  CAS  PubMed  Google Scholar 

  41. Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, et al. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell. 2009;4(6):472–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, et al. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol. 2008;26(11):1269–75.

    Article  CAS  PubMed  Google Scholar 

  43. Ichida JK, Blanchard J, Lam K, Son EY, Chung JE, Egli D, et al. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell. 2009;5(5):491–503.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Lin T, Ambasudhan R, Yuan X, Li W, Hilcove S, Abujarour R, et al. A chemical platform for improved induction of human iPSCs. Nat Methods. 2009;6(11):805–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Marson A, Foreman R, Chevalier B, Bilodeau S, Kahn M, Young RA, et al. Wnt signaling promotes reprogramming of somatic cells to pluripotency. Cell Stem Cell. 2008;3(2):132–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Shi Y, Do JT, Desponts C, Hahm HS, Scholer HR, Ding S. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell. 2008;2(6):525–8.

    Article  CAS  PubMed  Google Scholar 

  47. Chin MH, Mason MJ, Xie W, Volinia S, Singer M, Peterson C, et al. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell. 2009;5(1):111–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Deng C, Wynshaw-Boris A, Zhou F, Kuo A, Leder P. Fibroblast growth factor receptor 3 is a negative regulator of bone growth. Cell. 1996;84(6):911–21.

    Article  CAS  PubMed  Google Scholar 

  49. Doi A, Park IH, Wen B, Murakami P, Aryee MJ, Irizarry R, et al. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat Genet. 2009;41(12):1350–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Ghosh Z, Wilson KD, Wu Y, Hu S, Quertermous T, Wu JC. Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells. PLoS One. 2010;5(2):e8975.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Marchetto MC, Yeo GW, Kainohana O, Marsala M, Gage FH, Muotri AR. Transcriptional signature and memory retention of human-induced pluripotent stem cells. PLoS One. 2009;4(9):e7076.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature. 2011;471(7336):68–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Ohi Y, Qin H, Hong C, Blouin L, Polo JM, Guo T, et al. Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat Cell Biol. 2011;13(5):541–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Bock C, Kiskinis E, Verstappen G, Gu H, Boulting G, Smith ZD, et al. Reference maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell. 2011;144(3):439–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Guenther MG, Frampton GM, Soldner F, Hockemeyer D, Mitalipova M, Jaenisch R, et al. Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. Cell Stem Cell. 2010;7(2):249–57.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Newman AM, Cooper JB. Lab-specific gene expression signatures in pluripotent stem cells. Cell Stem Cell. 2010;7(2):258–62.

    Article  CAS  PubMed  Google Scholar 

  57. Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 2008;321(5893):1218–21.

    Article  CAS  PubMed  Google Scholar 

  58. Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, et al. Disease-specific induced pluripotent stem cells. Cell. 2008;134(5):877–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Merkle FT, Eggan K. Modeling human disease with pluripotent stem cells: from genome association to function. Cell Stem Cell. 2013;12(6):656–68.

    Article  CAS  PubMed  Google Scholar 

  60. Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science. 2007;318(5858):1920–3.

    Article  CAS  PubMed  Google Scholar 

  61. Raya A, Rodriguez-Piza I, Guenechea G, Vassena R, Navarro S, Barrero MJ, et al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature. 2009;460(7251):53–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Matsumoto Y, Hayashi Y, Schlieve CR, Ikeya M, Kim H, Nguyen TD, et al. Induced pluripotent stem cells from patients with human fibrodysplasia ossificans progressiva show increased mineralization and cartilage formation. Orphanet J Rare Dis. 2013;8:190.

    Article  PubMed Central  PubMed  Google Scholar 

  63. Lee DF, Su J, Kim HS, Chang B, Papatsenko D, Zhao R, et al. Modeling familial cancer with induced pluripotent stem cells. Cell. 2015;161(2):240–54.

    Article  CAS  PubMed  Google Scholar 

  64. Fox IJ, Daley GQ, Goldman SA, Huard J, Kamp TJ, Trucco M. Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease. Science. 2014;345(6199):1247391. This article reviews the potential clinical applications of iPSC technology to regenerative medicine.

    Article  PubMed Central  PubMed  Google Scholar 

  65. Li F, Bronson S, Niyibizi C. Derivation of murine induced pluripotent stem cells (iPS) and assessment of their differentiation toward osteogenic lineage. J Cell Biochem. 2010;109(4):643–52.

    Article  CAS  PubMed  Google Scholar 

  66. Tashiro K, Inamura M, Kawabata K, Sakurai F, Yamanishi K, Hayakawa T, et al. Efficient adipocyte and osteoblast differentiation from mouse induced pluripotent stem cells by adenoviral transduction. Stem Cells. 2009;27(8):1802–11.

    Article  CAS  PubMed  Google Scholar 

  67. Lian Q, Zhang Y, Zhang J, Zhang HK, Wu X, Zhang Y, et al. Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation. 2010;121(9):1113–23.

    Article  PubMed  Google Scholar 

  68. Bilousova G, du Jun H, King KB, De Langhe S, Chick WS, Torchia EC, et al. Osteoblasts derived from induced pluripotent stem cells form calcified structures in scaffolds both in vitro and in vivo. Stem Cells. 2011;29(2):206–16.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Egusa H, Kayashima H, Miura J, Uraguchi S, Wang F, Okawa H, et al. Comparative analysis of mouse-induced pluripotent stem cells and mesenchymal stem cells during osteogenic differentiation in vitro. Stem Cells Dev. 2014;23(18):2156–69.

    Article  CAS  PubMed  Google Scholar 

  70. Phillips MD, Kuznetsov SA, Cherman N, Park K, Chen KG, McClendon BN, et al. Directed differentiation of human induced pluripotent stem cells toward bone and cartilage: in vitro versus in vivo assays. Stem Cells Transl Med. 2014;3(7):867–78. This article compared the osteogenic differentiation capacity of iPSCs from fibroblasts vs bone marrow stromal cells, assayed by both in vitro and in vivo methods.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Kato H, Ochiai-Shino H, Onodera S, Saito A, Shibahara T, Azuma T. Promoting effect of 1,25(OH)2 vitamin D3 in osteogenic differentiation from induced pluripotent stem cells to osteocyte-like cells. Open Bio. 2015;5(2):140201.

    Article  Google Scholar 

  72. Li CH, Amar S. Inhibition of SFRP1 reduces severity of periodontitis. J Dent Res. 2007;86(9):873–7.

    Article  CAS  PubMed  Google Scholar 

  73. Ochiai-Shino H, Kato H, Sawada T, Onodera S, Saito A, Takato T, et al. A novel strategy for enrichment and isolation of osteoprogenitor cells from induced pluripotent stem cells based on surface marker combination. PLoS One. 2014;9(6):e99534.

    Article  PubMed Central  PubMed  Google Scholar 

  74. Kanke K, Masaki H, Saito T, Komiyama Y, Hojo H, Nakauchi H, et al. Stepwise differentiation of pluripotent stem cells into osteoblasts using four small molecules under serum-free and feeder-free conditions. Stem Cell Rep. 2014;2(6):751–60. This article reported the use of small molecule compounds to recapitulate the developmental stages of osteoblast differentiation starting with pluripotent stem cells.

    Article  CAS  Google Scholar 

  75. de Peppo GM, Marcos-Campos I, Kahler DJ, Alsalman D, Shang L, Vunjak-Novakovic G, et al. Engineering bone tissue substitutes from human induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2013;110(21):8680–5.

    Article  PubMed Central  PubMed  Google Scholar 

  76. Jin GZ, Kim TH, Kim JH, Won JE, Yoo SY, Choi SJ, et al. Bone tissue engineering of induced pluripotent stem cells cultured with macrochanneled polymer scaffold. J Biomed Mater Res A. 2013;101(5):1283–91.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  78. Xu J, Du Y, Deng H. Direct lineage reprogramming: strategies, mechanisms, and applications. Cell Stem Cell. 2015;16(2):119–34.

    Article  CAS  PubMed  Google Scholar 

  79. Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature. 2008;455(7213):627–32.

    Article  CAS  PubMed  Google Scholar 

  80. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010;463(7284):1035–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, et al. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature. 2011;475(7356):386–9.

    Article  CAS  PubMed  Google Scholar 

  82. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 2010;142(3):375–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Szabo E, Rampalli S, Risueno RM, Schnerch A, Mitchell R, Fiebig-Comyn A, et al. Direct conversion of human fibroblasts to multilineage blood progenitors. Nature. 2010;468(7323):521–6.

    Article  CAS  PubMed  Google Scholar 

  84. Jayawardena TM, Egemnazarov B, Finch EA, Zhang L, Payne JA, Pandya K, et al. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res. 2012;110(11):1465–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Song K, Nam YJ, Luo X, Qi X, Tan W, Huang GN, et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. 2012;485(7400):599–604.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Torper O, Pfisterer U, Wolf DA, Pereira M, Lau S, Jakobsson J, et al. Generation of induced neurons via direct conversion in vivo. Proc Natl Acad Sci U S A. 2013;110(17):7038–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Evans ND, Swain RJ, Gentleman E, Gentleman MM, Stevens MM. Gene-expression analysis reveals that embryonic stem cells cultured under osteogenic conditions produce mineral non-specifically compared to marrow stromal cells or osteoblasts. Eur Cell Mater. 2012;24:211–23.

    CAS  PubMed  Google Scholar 

  89. Yu Y, Al-Mansoori L, Opas M. Optimized osteogenic differentiation protocol from R1 mouse embryonic stem cells in vitro. Differentiation. 2015;89(1–2):1–10.

    Article  CAS  PubMed  Google Scholar 

  90. Kim MJ, Park JS, Kim S, Moon SH, Yang HN, Park KH, et al. Encapsulation of bone morphogenic protein-2 with Cbfa1-overexpressing osteogenic cells derived from human embryonic stem cells in hydrogel accelerates bone tissue regeneration. Stem Cells Dev. 2011;20(8):1349–58.

    Article  CAS  PubMed  Google Scholar 

  91. Tang M, Chen W, Liu J, Weir MD, Cheng L, Xu HH. Human induced pluripotent stem cell-derived mesenchymal stem cell seeding on calcium phosphate scaffold for bone regeneration. Tissue Eng Part A. 2014;20(7–8):1295–305.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Dr. Joy Y. Wu has received research support from the National Institute of Health and was funded by NIH grant OD008466.

Human and Animal Rights and Informed Consent

All studies by Dr. Joy Y. Wu involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

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  1. Division of Endocrinology, Stanford University School of Medicine, 300 Pasteur Dr., S-025, Stanford, CA, 94305, USA

    Joy Y. Wu

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Correspondence to Joy Y. Wu.

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This article is part of the Topical Collection on Skeletal Development

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Wu, J.Y. Pluripotent Stem Cells and Skeletal Regeneration—Promise and Potential. Curr Osteoporos Rep 13, 342–350 (2015). https://doi.org/10.1007/s11914-015-0285-9

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