Modulating the biochemical and biophysical culture environment to enhance osteogenic differentiation and maturation of human pluripotent stem cell-derived mesenchymal progenitors

Stem Cell Research and Therapy

Volumn 4, Issue 5, 2013, Pages

  De Peppo, Giuseppe Maria ^a   Marolt, Darja ^a  

^a New York Stem Cell Foundation Laboratory   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOMATERIAL; TISSUE SCAFFOLD;

ADULT STEM CELL; BIOREACTOR; BONE DEFECT; BONE DEVELOPMENT; BONE GRAFT; BONE REGENERATION; CELL DIFFERENTIATION; CELL FATE; CELL LINEAGE; CELL MATURATION; CELL PROLIFERATION; EMBRYONIC STEM CELL; HUMAN; MARFAN SYNDROME; MESENCHYMAL STEM CELL; NONHUMAN; OSTEOBLAST; OSTEOGENESIS IMPERFECTA; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REVIEW; STEM CELL CULTURE; TISSUE ENGINEERING; TISSUE REPAIR;

CELL DIFFERENTIATION; CULTURE MEDIA; HUMANS; MESENCHYMAL STROMAL CELLS; OSTEOGENESIS; PLURIPOTENT STEM CELLS; REGENERATIVE MEDICINE; SHEAR STRENGTH; TISSUE ENGINEERING;

EID: 84887946523     PISSN: None     EISSN: 17576512     Source Type: Journal    
DOI: 10.1186/scrt317     Document Type: Review

References (78)

1. Tissue engineering. Langer R, Vacanti JP, Science 1993 260 920 926 10.1126/science.8493529 8493529 (Pubitemid 23209960)
2. Bone repair in the twenty-first century: biology, chemistry or engineering? Hing KA, Philos Transact A Math Phys Eng Sci 2004 362 2821 2850 10.1098/rsta.2004.1466 (Pubitemid 40008008)
3. Bone graft substitutes. Laurencin C, Khan Y, El-Amin SF, Expert Rev Med Devices 2006 3 49 57 10.1586/17434440.3.1.49 16359252
4. Craniofacial reconstruction with bone and biomaterials: review over the last 11 years. Neovius E, Engstrand T, J Plast Reconstr Aesthet Surg 2010 63 1615 1623 10.1016/j.bjps.2009.06.003 19577527
5. Bone tissue engineering with human stem cells. Marolt D, Knezevic M, Novakovic GV, Stem Cell Res Ther 2010 1 10 10.1186/scrt10 20637059
6. Cell-based bone tissue engineering. Meijer GJ, de Bruijn JD, Koole R, van Blitterswijk CA, PLoS Med 2007 4 9 10.1371/journal.pmed.0040009 17311467 (Pubitemid 46354438)
7. Tissue engineered bone grafts: biological requirements, tissue culture and clinical relevance. Frohlich M, Grayson WL, Wan LQ, Marolt D, Drobnic M, Vunjak-Novakovic G, Curr Stem Cell Res Ther 2008 3 254 264 10.2174/ 157488808786733962 19075755
8. Human embryonic mesodermal progenitors highly resemble human mesenchymal stem cells and display high potential for tissue engineering applications. de Peppo GM, Svensson S, Lenneras M, Synnergren J, Stenberg J, Strehl R, Hyllner J, Thomsen P, Karlsson C, Tissue Eng Part A 2010 16 2161 2182 10.1089/ten.tea. 2009.0629 20136402
9. Replicative senescence of mesenchymal stem cells: a continuous and organized process. Wagner W, Horn P, Castoldi M, Diehlmann A, Bork S, Saffrich R, Benes V, Blake J, Pfister S, Eckstein V, Ho AD, PLoS One 2008 3 2213 10.1371/journal.pone.0002213 18493317
10. Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Zhou S, Greenberger JS, Epperly MW, Goff JP, Adler C, Leboff MS, Glowacki J, Aging Cell 2008 7 335 343 10.1111/j.1474-9726.2008.00377.x 18248663 (Pubitemid 351663902)
11. Effect of donor characteristics, technique of harvesting and in vitro processing on culturing of human marrow stroma cells for tissue engineered growth of bone. Bertram H, Mayer H, Schliephake H, Clin Oral Implants Res 2005 16 524 531 10.1111/j.1600-0501.2005.01142.x 16164457 (Pubitemid 43951439)
12. Embryonic stem cell lines derived from human blastocysts. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM, Science 1998 282 1145 1147 9804556 (Pubitemid 28516247)
13. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S, Cell 2007 131 861 872 10.1016/j.cell.2007.11.019 18035408 (Pubitemid 350138099)
14. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ, Cell Stem Cell 2010 7 618 630 10.1016/j.stem.2010.08.012 20888316
15. Generation of induced pluripotent stem cells using recombinant proteins. 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, Cell Stem Cell 2009 4 381 384 10.1016/j.stem.2009.04.005 19398399
16. Human embryonic stem cell-derived mesenchymal progenitors-potential in regenerative medicine. Karlsson C, Emanuelsson K, Wessberg F, Kajic K, Axell MZ, Eriksson PS, Lindahl A, Hyllner J, Strehl R, Stem Cell Res 2009 3 39 50 10.1016/j.scr.2009.05.002 19515621
17. Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Murry CE, Keller G, Cell 2008 132 661 680 10.1016/j.cell.2008.02.008 18295582 (Pubitemid 351260059)
18. Engineering bone tissue from human embryonic stem cells. Marolt D, Campos IM, Bhumiratana S, Koren A, Petridis P, Zhang G, Spitalnik PF, Grayson WL, Vunjak-Novakovic G, Proc Natl Acad Sci U S A 2012 109 8705 8709 10.1073/pnas.1201830109 22586099
19. Derivation of multipotent mesenchymal precursors from human embryonic stem cells. Barberi T, Willis LM, Socci ND, Studer L, PLoS Med 2005 2 161 10.1371/journal.pmed.0020161 15971941 (Pubitemid 40973509)
20. Differentiation of human embryonic stem cells into bipotent mesenchymal stem cells. Olivier EN, Rybicki AC, Bouhassira EE, Stem Cells 2006 24 1914 1922 10.1634/stemcells.2005-0648 16644919 (Pubitemid 44474167)
21. Derivation of clinically compliant MSCs from CD105+, CD24- differentiated human ESCs. Lian Q, Lye E, Suan Yeo K, Khia Way Tan E, Salto-Tellez M, Liu TM, Palanisamy N, El Oakley RM, Lee EH, Lim B, Lim SK, Stem Cells 2007 25 425 436 10.1634/stemcells.2006-0420 17053208 (Pubitemid 46232798)
22. In vivo commitment and functional tissue regeneration using human embryonic stem cell-derived mesenchymal cells. Hwang NS, Varghese S, Lee HJ, Zhang Z, Ye Z, Bae J, Cheng L, Elisseeff J, Proc Natl Acad Sci U S A 2008 105 20641 20646 10.1073/pnas.0809680106 19095799
23. Derivation of mesenchymal stem cells from human induced pluripotent stem cells cultured on synthetic substrates. Villa-Diaz LG, Brown SE, Liu Y, Ross AM, Lahann J, Parent JM, Krebsbach PH, Stem Cells 2012 30 1174 1181 10.1002/stem.1084 22415987
24. Human embryonic stem cell-derived mesodermal progenitors display substantially increased tissue formation compared to human mesenchymal stem cells under dynamic culture conditions in a packed bed/column bioreactor. de Peppo GM, Sladkova M, Sjovall P, Palmquist A, Oudina K, Hyllner J, Thomsen P, Petite H, Karlsson C, Tissue Eng Part A 2013 19 175 187 10.1089/ten.tea.2011. 0412 22924642
25. In vivo bone formation from human embryonic stem cell-derived osteogenic cells in poly(d,l-lactic-co-glycolic acid)/hydroxyapatite composite scaffolds. Kim S, Kim SS, Lee SH, Eun Ahn S, Gwak SJ, Song JH, Kim BS, Chung HM, Biomaterials 2008 29 1043 1053 10.1016/j.biomaterials.2007.11.005 18023477 (Pubitemid 350296313)
26. In vivo directed differentiation of pluripotent stem cells for skeletal regeneration. Levi B, Hyun JS, Montoro DT, Lo DD, Chan CK, Hu S, Sun N, Lee M, Grova M, Connolly AJ, Wu JC, Gurtner GC, Weissman IL, Wan DC, Longaker MT, Proc Natl Acad Sci U S A 2012 109 20379 20384 10.1073/pnas.1218052109 23169671
27. Bone-grafting and bone-graft substitutes. Finkemeier CG, J Bone Joint Surg Am 2002 84-A 454 464 11886919 (Pubitemid 37107720)
28. Bioreactor cultivation of osteochondral grafts. Vunjak-Novakovic G, Meinel L, Altman G, Kaplan D, Orthod Craniofac Res 2005 8 209 218 10.1111/j.1601-6343.2005.00334.x 16022723
29. In vitro platforms for tissue engineering: implications for basic research and clinical translation. Rouwkema J, Gibbs S, Lutolf MP, Martin I, Vunjak-Novakovic G, Malda J, J Tissue Eng Regen Med 2011 5 164 e167 10.1002/term.414 21774080
30. Bioreactor engineering of stem cell environments. Tandon N, Marolt D, Cimetta E, Vunjak-Novakovic G, Biotechnol Adv 2013 pii: S0734-9750(13)00066-9
31. Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. Bruder SP, Fink DJ, Caplan AI, J Cell Biochem 1994 56 283 294 7876320 (Pubitemid 24360045)
32. Human adipose-derived stem cells (hASCs) proliferate and differentiate in osteoblast-like cells on trabecular titanium scaffolds. Gastaldi G, Asti A, Scaffino MF, Visai L, Saino E, Cometa AM, Benazzo F, J Biomed Mater Res A 2010 94 790 799 20336739
33. The combined bone forming capacity of human periosteal derived cells and calcium phosphates. Roberts SJ, Geris L, Kerckhofs G, Desmet E, Schrooten J, Luyten FP, Biomaterials 2011 32 4393 4405 10.1016/j.biomaterials.2011.02.047 21421268
34. Société Française de Greffe de Moelle et Thérapie Cellulaire: Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Tarte K, Gaillard J, Lataillade JJ, Fouillard L, Becker M, Mossafa H, Tchirkov A, Rouard H, Henry C, Splingard M, Dulong J, Monnier D, Gourmelon P, Gorin NC, Sensebé L, Blood 2010 115 1549 1553 10.1182/blood-2009-05-219907 20032501
35. Heterogeneity of mesenchymal stromal cell preparations. Ho AD, Wagner W, Franke W, Cytotherapy 2008 10 320 330 10.1080/14653240802217011 18574765 (Pubitemid 351983156)
36. Mesenchymal stem cell preparations-comparing apples and oranges. Wagner W, Ho AD, Stem Cell Rev 2007 3 239 248 10.1007/s12015-007-9001-1 18074246 (Pubitemid 351526200)
37. Matrix-mediated retention of in vitro osteogenic differentiation potential and in vivo bone-forming capacity by human adult bone marrow-derived mesenchymal stem cells during ex vivo expansion. Mauney JR, Kirker-Head C, Abrahamson L, Gronowicz G, Volloch V, Kaplan DL, J Biomed Mater Res A 2006 79 464 475 16752403 (Pubitemid 44845159)
38. Expansion of mesenchymal stem cells isolated from pediatric and adult donor bone marrow. Mareschi K, Ferrero I, Rustichelli D, Aschero S, Gammaitoni L, Aglietta M, Madon E, Fagioli F, J Cell Biochem 2006 97 744 754 10.1002/jcb.20681 16229018
39. In vitro differentiation and in vivo mineralization of osteogenic cells derived from human embryonic stem cells. Bielby RC, Boccaccini AR, Polak JM, Buttery LD, Tissue Eng 2004 10 1518 1525 15588411 (Pubitemid 39557855)
40. Effect of osteogenic induction on the in vitro differentiation of human embryonic stem cells cocultured with periodontal ligament fibroblasts. Inanc B, Elcin AE, Elcin YM, Artif Organs 2007 31 792 800 10.1111/j.1525-1594.2007.00470. x 18273446 (Pubitemid 350131991)
41. Cultivation of human embryonic stem cells without the embryoid body step enhances osteogenesis in vitro. Karp JM, Ferreira LS, Khademhosseini A, Kwon AH, Yeh J, Langer RS, Stem Cells 2006 24 835 843 10.1634/stemcells.2005-0383 16253980 (Pubitemid 44464716)
42. Human embryonic stem cells possess immune-privileged properties. Li L, Baroja ML, Majumdar A, Chadwick K, Rouleau A, Gallacher L, Ferber I, Lebkowski J, Martin T, Madrenas J, Bhatia M, Stem Cells 2004 22 448 456 10.1634/stemcells.22-4-448 15277692 (Pubitemid 39014562)
43. Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. Swijnenburg RJ, Schrepfer S, Govaert JA, Cao F, Ransohoff K, Sheikh AY, Haddad M, Connolly AJ, Davis MM, Robbins RC, Wu JC, Proc Natl Acad Sci U S A 2008 105 12991 12996 10.1073/pnas.0805802105 18728188
44. Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-beta/activin/nodal signaling using SB-431542. Mahmood A, Harkness L, Schroder HD, Abdallah BM, Kassem M, J Bone Miner Res 2010 25 1216 1233 10.1002/jbmr.34 20200949
45. Comparison of osteogenesis of human embryonic stem cells within 2D and 3D culture systems. Tian XF, Heng BC, Ge Z, Lu K, Rufaihah AJ, Fan VT, Yeo JF, Cao T, Scand J Clin Lab Invest 2008 68 58 67 10.1080/00365510701466416 18224557 (Pubitemid 351161514)
46. Primary bone-derived cells induce osteogenic differentiation without exogenous factors in human embryonic stem cells. Ahn SE, Kim S, Park KH, Moon SH, Lee HJ, Kim GJ, Lee YJ, Cha KY, Chung HM, Biochem Biophys Res Commun 2006 340 403 408 10.1016/j.bbrc.2005.12.020 16389066 (Pubitemid 43021762)
47. In vivo bone formation by progeny of human embryonic stem cells. Kuznetsov SA, Cherman N, Robey PG, Stem Cells Dev 2011 20 269 287 10.1089/scd.2009.0501 20590404
48. Human embryonic stem cell-derived mesoderm-like epithelium transitions to mesenchymal progenitor cells. Boyd NL, Robbins KR, Dhara SK, West FD, Stice SL, Tissue Eng Part A 2009 15 1897 1907 10.1089/ten.tea.2008.0351 19196144
49. Enrichment of human ESC-derived multipotent mesenchymal stem cells with immunosuppressive and anti-inflammatory properties capable to protect against experimental inflammatory bowel disease. Sánchez L, Gutierrez-Aranda I, Ligero G, Rubio R, Muñoz-López M, García-Pérez JL, Ramos V, Real PJ, Bueno C, Rodríguez R, Delgado M, Menendez P, Stem Cells 2011 29 251 262 10.1002/stem.569 21732483
50. Efficient differentiation of human pluripotent stem cells into mesenchymal stem cells by modulating intracellular signaling pathways in a feeder/serum-free system. Tran NT, Trinh QM, Lee GM, Han YM, Stem Cells Dev 2012 21 1165 1175 10.1089/scd.2011.0346 21793661
51. Engineering bone tissue substitutes from human induced pluripotent stem cells. de Peppo GM, Marcos-Campos I, Kahler D, Alsalman D, Shang L, Vunjak-Novakovic G, Marolt D, Proc Natl Acad Sci U S A 2013 110 8680 8685 10.1073/pnas.1301190110 23653480
52. Expansion and maintenance of human embryonic stem cell-derived endothelial cells by TGFbeta inhibition is Id1 dependent. James D, Nam HS, Seandel M, Nolan D, Janovitz T, Tomishima M, Studer L, Lee G, Lyden D, Benezra R, Zaninovic N, Rosenwaks Z, Rabbany SY, Rafii S, Nat Biotechnol 2010 28 161 166 10.1038/nbt.1605 20081865
53. Human cardiovascular progenitor cells develop from a KDR + embryonic-stem-cell-derived population. Yang L, Soonpaa MH, Adler ED, Roepke TK, Kattman SJ, Kennedy M, Henckaerts E, Bonham K, Abbott GW, Linden RM, Field LJ, Keller GM, Nature 2008 453 524 528 10.1038/nature06894 18432194 (Pubitemid 351733312)
54. The influence of scaffold elasticity on germ layer specification of human embryonic stem cells. Zoldan J, Karagiannis ED, Lee CY, Anderson DG, Langer R, Levenberg S, Biomaterials 2011 32 9612 9621 10.1016/j.biomaterials.2011.09.012 21963156
55. Soft microenvironments promote the early neurogenic differentiation but not self-renewal of human pluripotent stem cells. Keung AJ, Asuri P, Kumar S, Schaffer DV, Integr Biol (Camb) 2012 4 1049 1058 10.1039/c2ib20083j
56. Generation of human embryonic stem cell-derived mesoderm and cardiac cells using size-specified aggregates in an oxygen-controlled bioreactor. Niebruegge S, Bauwens CL, Peerani R, Thavandiran N, Masse S, Sevaptisidis E, Nanthakumar K, Woodhouse K, Husain M, Kumacheva E, Zandstra PW, Biotechnol Bioeng 2009 102 493 507 10.1002/bit.22065 18767184
57. Hydrodynamic modulation of embryonic stem cell differentiation by rotary orbital suspension culture. Sargent CY, Berguig GY, Kinney MA, Hiatt LA, Carpenedo RL, Berson RE, McDevitt TC, Biotechnol Bioeng 2010 105 611 626 10.1002/bit.22578 19816980
58. Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis. Riekstina U, Cakstina I, Parfejevs V, Hoogduijn M, Jankovskis G, Muiznieks I, Muceniece R, Ancans J, Stem Cell Rev 2009 5 378 386 10.1007/s12015-009-9094-9 20058201
59. Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery. Giuliani M, Oudrhiri N, Noman ZM, Vernochet A, Chouaib S, Azzarone B, Durrbach A, Bennaceur-Griscelli A, Blood 2011 118 3254 3262 10.1182/blood-2010-12-325324 21803852
60. Osteogenic potential of human mesenchymal stem cells and human embryonic stem cell-derived mesodermal progenitors: a tissue engineering perspective. de Peppo GM, Sjovall P, Lenneras M, Strehl R, Hyllner J, Thomsen P, Karlsson C, Tissue Eng Part A 2010 16 3413 3426 10.1089/ten.tea.2010.0052 20536357
61. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Dalby MJ, Gadegaard N, Tare R, Andar A, Riehle MO, Herzyk P, Wilkinson CD, Oreffo RO, Nat Mater 2007 6 997 1003 10.1038/nmat2013 17891143 (Pubitemid 350210577)
62. Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells. Shih YR, Tseng KF, Lai HY, Lin CH, Lee OK, J Bone Miner Res 2011 26 730 738 10.1002/jbmr.278 20939067
63. Porosity of 3D biomaterial scaffolds and osteogenesis. Karageorgiou V, Kaplan D, Biomaterials 2005 26 5474 5491 10.1016/j.biomaterials.2005.02.002 15860204 (Pubitemid 40592136)
64. Engineering RGD nanopatterned hydrogels to control preosteoblast behavior: a combined computational and experimental approach. Comisar WA, Kazmers NH, Mooney DJ, Linderman JJ, Biomaterials 2007 28 4409 4417 10.1016/j.biomaterials.2007.06.018 17619056 (Pubitemid 47214638)
65. Material-tissue interfaces: the role of surface properties and processes. Kasemo B, Lausmaa J, Environ Health Perspect 1994 102 41 45 7851329 (Pubitemid 24364823)
66. Controlling self-renewal and differentiation of stem cells via mechanical cues. Nava MM, Raimondi MT, Pietrabissa R, J Biomed Biotechnol 2012 2012 797410 23091358
67. Bone scaffold architecture modulates the development of mineralized bone matrix by human embryonic stem cells. Marcos-Campos I, Marolt D, Petridis P, Bhumiratana S, Schmidt D, Vunjak-Novakovic G, Biomaterials 2012 33 8329 8342 10.1016/j.biomaterials.2012.08.013 22901965
68. Response of human embryonic stem cell-derived mesenchymal stem cells to osteogenic factors and architectures of materials during in vitro osteogenesis. Hu J, Smith LA, Feng K, Liu X, Sun H, Ma PX, Tissue Eng Part A 2010 16 3507 3514 10.1089/ten.tea.2010.0097 20594153
69. Modulation of embryonic mesenchymal progenitor cell differentiation via control over pure mechanical modulus in electrospun nanofibers. Nam J, Johnson J, Lannutti JJ, Agarwal S, Acta Biomater 2011 7 1516 1524 10.1016/j.actbio.2010. 11.022 21109030
70. Biomaterials directed in vivo osteogenic differentiation of mesenchymal cells derived from human embryonic stem cells. Hwang NS, Varghese S, Lee JH, Zhang Z, Elisseeff J, Tissue Eng Part A 2013 19 1723 1732 10.1089/ten.tea.2013. 0064 23510052
71. Mineralized matrix deposition by marrow stromal osteoblasts in 3D perfusion culture increases with increasing fluid shear forces. Sikavitsas VI, Bancroft GN, Holtorf HL, Jansen JA, Mikos AG, Proc Natl Acad Sci U S A 2003 100 14683 14688 10.1073/pnas.2434367100 14657343 (Pubitemid 37517951)
72. Short bouts of mechanical loading are as effective as dexamethasone at inducing matrix production by human bone marrow mesenchymal stem cell. Sittichokechaiwut A, Edwards JH, Scutt AM, Reilly GC, Eur Cell Mater 2010 20 45 57 20648425
73. Optimizing the medium perfusion rate in bone tissue engineering bioreactors. Grayson WL, Marolt D, Bhumiratana S, Frohlich M, Guo XE, Vunjak-Novakovic G, Biotechnol Bioeng 2011 108 1159 1170 10.1002/bit.23024 21449028
74. Bone tissue engineering bioreactors: a role in the clinic? Salter E, Goh B, Hung B, Hutton D, Ghone N, Grayson WL, Tissue Eng Part B Rev 2012 18 62 75 21902622
75. Artificial niche microarrays for probing single stem cell fate in high throughput. Gobaa S, Hoehnel S, Roccio M, Negro A, Kobel S, Lutolf MP, Nat Methods 2011 8 949 955 10.1038/nmeth.1732 21983923
76. Micro-bioreactor array for controlling cellular microenvironments. Figallo E, Cannizzaro C, Gerecht S, Burdick JA, Langer R, Elvassore N, Vunjak-Novakovic G, Lab Chip 2007 7 710 719 10.1039/b700063d 17538712 (Pubitemid 46850685)
77. Skeletogenic phenotype of human Marfan embryonic stem cells faithfully phenocopied by patient-specific induced-pluripotent stem cells. Quarto N, Leonard B, Li S, Marchand M, Anderson E, Behr B, Francke U, Reijo-Pera R, Chiao E, Longaker MT, Proc Natl Acad Sci U S A 2012 109 215 220 10.1073/pnas. 1113442109 22178754
78. Normal collagen and bone production by gene-targeted human osteogenesis imperfecta iPSCs. Deyle DR, Khan IF, Ren G, Wang PR, Kho J, Schwarze U, Russell DW, Mol Ther 2012 20 204 213 10.1038/mt.2011.209 22031238