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Stem Cells International
Volume 2018, Article ID 6726185, 10 pages
https://doi.org/10.1155/2018/6726185
Review Article

Current Strategies to Generate Human Mesenchymal Stem Cells In Vitro

Institute for Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Essen, Germany

Correspondence should be addressed to Diana Klein; ed.nesse-ku@nielk.anaid

Received 26 April 2018; Revised 31 July 2018; Accepted 9 August 2018; Published 26 August 2018

Academic Editor: Stan Gronthos

Copyright © 2018 Jennifer Steens and Diana Klein. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. P. Chidgey, D. Layton, A. Trounson, and R. L. Boyd, “Tolerance strategies for stem-cell-based therapies,” Nature, vol. 453, no. 7193, pp. 330–337, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. B. Kristjansson and S. Honsawek, “Current perspectives in mesenchymal stem cell therapies for osteoarthritis,” Stem Cells International, vol. 2014, Article ID 194318, 13 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Rafii and D. Lyden, “Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration,” Nature Medicine, vol. 9, no. 6, pp. 702–712, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Uccelli, L. Moretta, and V. Pistoia, “Mesenchymal stem cells in health and disease,” Nature Reviews Immunology, vol. 8, no. 9, pp. 726–736, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. I. B. Copland, “Mesenchymal stromal cells for cardiovascular disease,” Journal of Cardiovascular Disease Research, vol. 2, no. 1, pp. 3–13, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. K. Komatsu, O. Honmou, J. Suzuki, K. Houkin, H. Hamada, and J. D. Kocsis, “Therapeutic time window of mesenchymal stem cells derived from bone marrow after cerebral ischemia,” Brain Research, vol. 1334, pp. 84–92, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. Z. Wen, S. Zheng, C. Zhou, J. Wang, and T. Wang, “Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction,” Journal of Cellular and Molecular Medicine, vol. 15, no. 5, pp. 1032–1043, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. W. R. Otto and N. A. Wright, “Mesenchymal stem cells: from experiment to clinic,” Fibrogenesis & Tissue Repair, vol. 4, no. 1, p. 20, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. R. R. Sharma, K. Pollock, A. Hubel, and D. McKenna, “Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices,” Transfusion, vol. 54, no. 5, pp. 1418–1437, 2014. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Dominici, K. le Blanc, I. Mueller et al., “Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement,” Cytotherapy, vol. 8, no. 4, pp. 315–317, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. V. B. Fernandez Vallone, M. A. Romaniuk, H. Choi, V. Labovsky, J. Otaegui, and N. A. Chasseing, “Mesenchymal stem cells and their use in therapy: what has been achieved?” Differentiation, vol. 85, no. 1-2, pp. 1–10, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Conese, A. Carbone, S. Castellani, and S. Di Gioia, “Paracrine effects and heterogeneity of marrow-derived stem/progenitor cells: relevance for the treatment of respiratory diseases,” Cells, Tissues, Organs, vol. 197, no. 6, pp. 445–473, 2013. View at Publisher · View at Google Scholar · View at Scopus
  13. A. De Becker and I. V. Riet, “Homing and migration of mesenchymal stromal cells: how to improve the efficacy of cell therapy?” World Journal of Stem Cells, vol. 8, no. 3, pp. 73–87, 2016. View at Publisher · View at Google Scholar
  14. J. Leibacher and R. Henschler, “Biodistribution, migration and homing of systemically applied mesenchymal stem/stromal cells,” Stem Cell Research & Therapy, vol. 7, no. 1, p. 7, 2016. View at Publisher · View at Google Scholar · View at Scopus
  15. E. Mariani and A. Facchini, “Clinical applications and biosafety of human adult mesenchymal stem cells,” Current Pharmaceutical Design, vol. 18, no. 13, pp. 1821–1845, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Wang, X. Qu, and R. C. Zhao, “Clinical applications of mesenchymal stem cells,” Journal of Hematology & Oncology, vol. 5, no. 1, p. 19, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. P. Bader, Z. Kuçi, S. Bakhtiar et al., “Effective treatment of steroid and therapy-refractory acute graft-versus-host disease with a novel mesenchymal stromal cell product (MSC-FFM),” Bone Marrow Transplantation, vol. 53, no. 7, pp. 852–862, 2018. View at Publisher · View at Google Scholar · View at Scopus
  18. P. Connick and S. Chandran, “Mesenchymal stromal cell transplantation modulates neuroinflammatory milieu in amyotrophic lateral sclerosis,” Cytotherapy, vol. 16, no. 8, pp. 1031-1032, 2014. View at Publisher · View at Google Scholar · View at Scopus
  19. P. Connick, M. Kolappan, C. Crawley et al., “Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study,” The Lancet Neurology, vol. 11, no. 2, pp. 150–156, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Fujii, Y. Miura, A. Fujishiro et al., “Graft-versus-host disease amelioration by human bone marrow mesenchymal stromal/stem cell-derived extracellular vesicles is associated with peripheral preservation of naive T cell populations,” Stem Cells, vol. 36, no. 3, pp. 434–445, 2018. View at Publisher · View at Google Scholar · View at Scopus
  21. F. Marofi, G. Vahedi, A. Biglari, A. Esmaeilzadeh, and S. S. Athari, “Mesenchymal stromal/stem cells: a new era in the cell-based targeted gene therapy of cancer,” Frontiers in Immunology, vol. 8, article 1770, 2017. View at Publisher · View at Google Scholar · View at Scopus
  22. E. K. Sage, R. M. Thakrar, and S. M. Janes, “Genetically modified mesenchymal stromal cells in cancer therapy,” Cytotherapy, vol. 18, no. 11, pp. 1435–1445, 2016. View at Publisher · View at Google Scholar · View at Scopus
  23. Y. Yu, Y. Liu, C. Zong et al., “Mesenchymal stem cells with Sirt1 overexpression suppress breast tumor growth via chemokine-dependent natural killer cells recruitment,” Scientific Reports, vol. 6, no. 1, article 35998, 2016. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Crisan, S. Yap, L. Casteilla et al., “A perivascular origin for mesenchymal stem cells in multiple human organs,” Cell Stem Cell, vol. 3, no. 3, pp. 301–313, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. D. Klein, P. Weisshardt, V. Kleff, H. Jastrow, H. G. Jakob, and S. Ergun, “Vascular wall-resident CD44+ multipotent stem cells give rise to pericytes and smooth muscle cells and contribute to new vessel maturation,” PLoS One, vol. 6, no. 5, article e20540, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. M. F. Pittenger, A. M. Mackay, S. C. Beck et al., “Multilineage potential of adult human mesenchymal stem cells,” Science, vol. 284, no. 5411, pp. 143–147, 1999. View at Publisher · View at Google Scholar · View at Scopus
  27. V. Tirino, F. Paino, R. d’Aquino, V. Desiderio, A. de Rosa, and G. Papaccio, “Methods for the identification, characterization and banking of human DPSCs: current strategies and perspectives,” Stem Cell Reviews, vol. 7, no. 3, pp. 608–615, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. S. A. Wexler, C. Donaldson, P. Denning-Kendall, C. Rice, B. Bradley, and J. M. Hows, “Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not,” British Journal of Haematology, vol. 121, no. 2, pp. 368–374, 2003. View at Publisher · View at Google Scholar · View at Scopus
  29. W. Zhao, D. G. Phinney, D. Bonnet, M. Dominici, and M. Krampera, “Mesenchymal stem cell biodistribution, migration, and homing in vivo,” Stem Cells International, vol. 2014, Article ID 292109, 2 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  30. P. J. Ho, M. L. Yen, B. C. Tang, C. T. Chen, and B. L. Yen, “H2O2 accumulation mediates differentiation capacity alteration, but not proliferative decline, in senescent human fetal mesenchymal stem cells,” Antioxidants & Redox Signaling, vol. 18, no. 15, pp. 1895–1905, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. C. Kyriakou, N. Rabin, A. Pizzey, A. Nathwani, and K. Yong, “Factors that influence short-term homing of human bone marrow-derived mesenchymal stem cells in a xenogeneic animal model,” Haematologica, vol. 93, no. 10, pp. 1457–1465, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. Y. Liu, A. J. Goldberg, J. E. Dennis, G. A. Gronowicz, and L. T. Kuhn, “One-step derivation of mesenchymal stem cell (MSC)-like cells from human pluripotent stem cells on a fibrillar collagen coating,” PLoS One, vol. 7, no. 3, article e33225, 2012. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Mimeault and S. K. Batra, “Recent insights into the molecular mechanisms involved in aging and the malignant transformation of adult stem/progenitor cells and their therapeutic implications,” Ageing Research Reviews, vol. 8, no. 2, pp. 94–112, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Miura, Y. Miura, H. M. Padilla-Nash et al., “Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation,” Stem Cells, vol. 24, no. 4, pp. 1095–1103, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. W. J. C. Rombouts and R. E. Ploemacher, “Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture,” Leukemia, vol. 17, no. 1, pp. 160–170, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Galipeau, “The mesenchymal stromal cells dilemma—does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road?” Cytotherapy, vol. 15, no. 1, pp. 2–8, 2013. View at Publisher · View at Google Scholar · View at Scopus
  37. E. A. Kimbrel, N. A. Kouris, G. J. Yavanian et al., “Mesenchymal stem cell population derived from human pluripotent stem cells displays potent immunomodulatory and therapeutic properties,” Stem Cells and Development, vol. 23, no. 14, pp. 1611–1624, 2014. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Tyndall, “Mesenchymal stem cell treatments in rheumatology: a glass half full?” Nature Reviews Rheumatology, vol. 10, no. 2, pp. 117–124, 2014. View at Publisher · View at Google Scholar · View at Scopus
  39. W. Wagner and A. D. Ho, “Mesenchymal stem cell preparations—comparing apples and oranges,” Stem Cell Reviews, vol. 3, no. 4, pp. 239–248, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. I. Budniatzky and L. Gepstein, “Concise review: reprogramming strategies for cardiovascular regenerative medicine: from induced pluripotent stem cells to direct reprogramming,” Stem Cells Translational Medicine, vol. 3, no. 4, pp. 448–457, 2014. View at Publisher · View at Google Scholar · View at Scopus
  41. D. Klein, “iPSCs-based generation of vascular cells: reprogramming approaches and applications,” Cellular and Molecular Life Sciences: CMLS, vol. 75, no. 8, pp. 1411–1433, 2018. View at Publisher · View at Google Scholar · View at Scopus
  42. L. Kurian, I. Sancho-Martinez, E. Nivet et al., “Conversion of human fibroblasts to angioblast-like progenitor cells,” Nature Methods, vol. 10, no. 1, pp. 77–83, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. C. Xu, J. Jiang, V. Sottile, J. McWhir, J. Lebkowski, and M. K. Carpenter, “Immortalized fibroblast-like cells derived from human embryonic stem cells support undifferentiated cell growth,” Stem Cells, vol. 22, no. 6, pp. 972–980, 2004. View at Publisher · View at Google Scholar
  44. S. Shi, S. Gronthos, S. Chen et al., “Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression,” Nature Biotechnology, vol. 20, no. 6, pp. 587–591, 2002. View at Publisher · View at Google Scholar · View at Scopus
  45. T. Barberi, L. M. Willis, N. D. Socci, and L. Studer, “Derivation of multipotent mesenchymal precursors from human embryonic stem cells,” PLoS Medicine, vol. 2, no. 6, article e161, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. Q. Lian, E. Lye, K. Suan Yeo et al., “Derivation of clinically compliant MSCs from CD105+, CD24− differentiated human ESCs,” Stem Cells, vol. 25, no. 2, pp. 425–436, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Ellerstrom, R. Strehl, K. Moya et al., “Derivation of a xeno-free human embryonic stem cell line,” Stem Cells, vol. 24, no. 10, pp. 2170–2176, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. C. Karlsson, K. Emanuelsson, F. Wessberg et al., “Human embryonic stem cell-derived mesenchymal progenitors—potential in regenerative medicine,” Stem Cell Research, vol. 3, no. 1, pp. 39–50, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. G. M. de Peppo, S. Svensson, M. Lenneras et al., “Human embryonic mesodermal progenitors highly resemble human mesenchymal stem cells and display high potential for tissue engineering applications,” Tissue Engineering Part A, vol. 16, no. 7, pp. 2161–2182, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. Y. Jung, G. Bauer, and J. A. Nolta, “Concise review: induced pluripotent stem cell-derived mesenchymal stem cells: progress toward safe clinical products,” Stem Cells, vol. 30, no. 1, pp. 42–47, 2012. View at Publisher · View at Google Scholar · View at Scopus
  51. T. Ma, M. Xie, T. Laurent, and S. Ding, “Progress in the reprogramming of somatic cells,” Circulation Research, vol. 112, no. 3, pp. 562–574, 2013. View at Publisher · View at Google Scholar · View at Scopus
  52. H. Okano, M. Nakamura, K. Yoshida et al., “Steps toward safe cell therapy using induced pluripotent stem cells,” Circulation Research, vol. 112, no. 3, pp. 523–533, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Frobel, H. Hemeda, M. Lenz et al., “Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells,” Stem Cell Reports, vol. 3, no. 3, pp. 414–422, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. C. Roux, G. Saviane, J. Pini et al., “Immunosuppressive mesenchymal stromal cells derived from human-induced pluripotent stem cells induce human regulatory T cells in vitro and in vivo,” Frontiers in Immunology, vol. 8, 2018. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Steens, M. Zuk, M. Benchellal et al., “In vitro generation of vascular wall-resident multipotent stem cells of mesenchymal nature from murine induced pluripotent stem cells,” Stem Cell Reports, vol. 8, no. 4, pp. 919–932, 2017. View at Publisher · View at Google Scholar · View at Scopus
  56. Q. Lian, Y. Zhang, J. Zhang et al., “Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice,” Circulation, vol. 121, no. 9, pp. 1113–1123, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Giuliani, N. Oudrhiri, Z. M. Noman et al., “Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery,” Blood, vol. 118, no. 12, pp. 3254–3262, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Zhang, Y. C. Chan, J. C. Y. Ho, C. W. Siu, Q. Lian, and H. F. Tse, “Regulation of cell proliferation of human induced pluripotent stem cell-derived mesenchymal stem cells via ether-à-go-go 1 (hEAG1) potassium channel,” American Journal of Physiology-Cell Physiology, vol. 303, no. 2, pp. C115–C125, 2012. View at Publisher · View at Google Scholar · View at Scopus
  59. D. Medici and A. Nawshad, “Type I collagen promotes epithelial-mesenchymal transition through ILK-dependent activation of NF-κB and LEF-1,” Matrix Biology, vol. 29, no. 3, pp. 161–165, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. Y. S. Chen, R. A. Pelekanos, R. L. Ellis, R. Horne, E. J. Wolvetang, and N. M. Fisk, “Small molecule mesengenic induction of human induced pluripotent stem cells to generate mesenchymal stem/stromal cells,” Stem Cells Translational Medicine, vol. 1, no. 2, pp. 83–95, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. K. Hynes, D. Menicanin, K. Mrozik, S. Gronthos, and P. M. Bartold, “Generation of functional mesenchymal stem cells from different induced pluripotent stem cell lines,” Stem Cells and Development, vol. 23, no. 10, pp. 1084–1096, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. C. Luzzani, G. Neiman, X. Garate et al., “A therapy-grade protocol for differentiation of pluripotent stem cells into mesenchymal stem cells using platelet lysate as supplement,” Stem Cell Research & Therapy, vol. 6, no. 1, p. 6, 2015. View at Publisher · View at Google Scholar · View at Scopus
  63. Y. Chen, B. Stevens, J. Chang, J. Milbrandt, B. A. Barres, and J. W. Hell, “NS21: re-defined and modified supplement B27 for neuronal cultures,” Journal of Neuroscience Methods, vol. 171, no. 2, pp. 239–247, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. A. Flemming, K. Schallmoser, D. Strunk, M. Stolk, H. D. Volk, and M. Seifert, “Immunomodulative efficacy of bone marrow-derived mesenchymal stem cells cultured in human platelet lysate,” Journal of Clinical Immunology, vol. 31, no. 6, pp. 1143–1156, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. P. Iudicone, D. Fioravanti, G. Bonanno et al., “Pathogen-free, plasma-poor platelet lysate and expansion of human mesenchymal stem cells,” Journal of Translational Medicine, vol. 12, no. 1, p. 28, 2014. View at Publisher · View at Google Scholar · View at Scopus
  66. S. Kinzebach, L. Dietz, H. Kluter, H. J. Thierse, and K. Bieback, “Functional and differential proteomic analyses to identify platelet derived factors affecting ex vivo expansion of mesenchymal stromal cells,” BMC Cell Biology, vol. 14, no. 1, p. 48, 2013. View at Publisher · View at Google Scholar · View at Scopus
  67. J. J. Auletta, E. A. Zale, J. F. Welter, and L. A. Solchaga, “Fibroblast growth factor-2 enhances expansion of human bone marrow-derived mesenchymal stromal cells without diminishing their immunosuppressive potential,” Stem Cells International, vol. 2011, Article ID 235176, 10 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. N. Fekete, M. Gadelorge, D. Fürst et al., “Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components,” Cytotherapy, vol. 14, no. 5, pp. 540–554, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. C. D. Luzzani and S. G. Miriuka, “Pluripotent stem cells as a robust source of mesenchymal stem cells,” Stem Cell Reviews, vol. 13, no. 1, pp. 68–78, 2017. View at Publisher · View at Google Scholar · View at Scopus
  70. D. Klein, M. Benchellal, V. Kleff, H. G. Jakob, and S. Ergun, “Hox genes are involved in vascular wall-resident multipotent stem cell differentiation into smooth muscle cells,” Scientific Reports, vol. 3, no. 1, article 2178, 2013. View at Publisher · View at Google Scholar · View at Scopus
  71. X. Meng, R. J. Su, D. J. Baylink et al., “Rapid and efficient reprogramming of human fetal and adult blood CD34+ cells into mesenchymal stem cells with a single factor,” Cell Research, vol. 23, no. 5, pp. 658–672, 2013. View at Publisher · View at Google Scholar · View at Scopus
  72. W. Chen, D. J. Baylink, K. H. William Lau, and X. B. Zhang, “Generation of mesenchymal stem cells by blood cell reprogramming,” Current Stem Cell Research & Therapy, vol. 11, no. 2, pp. 114–121, 2016. View at Publisher · View at Google Scholar · View at Scopus
  73. P. L. Lai, H. Lin, S. F. Chen et al., “Efficient generation of chemically induced mesenchymal stem cells from human dermal fibroblasts,” Scientific Reports, vol. 7, no. 1, article 44534, 2017. View at Publisher · View at Google Scholar · View at Scopus
  74. F. Gao, S. M. Chiu, D. A. L. Motan et al., “Mesenchymal stem cells and immunomodulation: current status and future prospects,” Cell Death & Disease, vol. 7, no. 1, article e2062, 2016. View at Publisher · View at Google Scholar · View at Scopus
  75. Y. J. Jeon, J. Kim, J. H. Cho, H. M. Chung, and J. I. Chae, “Comparative analysis of human mesenchymal stem cells derived from bone marrow, placenta, and adipose tissue as sources of cell therapy,” Journal of Cellular Biochemistry, vol. 117, no. 5, pp. 1112–1125, 2016. View at Publisher · View at Google Scholar · View at Scopus
  76. P. S. in 't Anker, W. A. Noort, S. A. Scherjon et al., “Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential,” Haematologica, vol. 88, no. 8, pp. 845–852, 2003. View at Google Scholar
  77. A. Ribeiro, P. Laranjeira, S. Mendes et al., “Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells,” Stem Cell Research & Therapy, vol. 4, no. 5, p. 125, 2013. View at Publisher · View at Google Scholar · View at Scopus
  78. J. J. Montesinos, E. Flores-Figueroa, S. Castillo-Medina et al., “Human mesenchymal stromal cells from adult and neonatal sources: comparative analysis of their morphology, immunophenotype, differentiation patterns and neural protein expression,” Cytotherapy, vol. 11, no. 2, pp. 163–176, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. S. J. Prasanna, D. Gopalakrishnan, S. R. Shankar, and A. B. Vasandan, “Pro-inflammatory cytokines, IFNγ and TNFα, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially,” PLoS One, vol. 5, no. 2, article e9016, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. X. Wang, E. A. Kimbrel, K. Ijichi et al., “Human ESC-derived MSCs outperform bone marrow MSCs in the treatment of an EAE model of multiple sclerosis,” Stem Cell Reports, vol. 3, no. 1, pp. 115–130, 2014. View at Publisher · View at Google Scholar · View at Scopus
  81. H. Wegmeyer, A. M. Bröske, M. Leddin et al., “Mesenchymal stromal cell characteristics vary depending on their origin,” Stem Cells and Development, vol. 22, no. 19, pp. 2606–2618, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. Z.-Y. Zhang, S. H. Teoh, M. S. K. Chong et al., “Superior osteogenic capacity for bone tissue engineering of fetal compared with perinatal and adult mesenchymal stem cells,” Stem Cells, vol. 27, no. 1, pp. 126–137, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. K. B. Ackema and J. Charite, “Mesenchymal stem cells from different organs are characterized by distinct topographic Hox codes,” Stem Cells and Development, vol. 17, no. 5, pp. 979–992, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. B. Sági, P. Maraghechi, V. S. Urbán et al., “Positional identity of murine mesenchymal stem cells resident in different organs is determined in the postsegmentation mesoderm,” Stem Cells and Development, vol. 21, no. 5, pp. 814–828, 2012. View at Publisher · View at Google Scholar · View at Scopus
  85. S. Liedtke, A. Buchheiser, J. Bosch et al., “The HOX code as a “biological fingerprint” to distinguish functionally distinct stem cell populations derived from cord blood,” Stem Cell Research, vol. 5, no. 1, pp. 40–50, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. Z. Hamidouche, K. Rother, J. Przybilla et al., “Bistable epigenetic states explain age-dependent decline in mesenchymal stem cell heterogeneity,” Stem Cells, vol. 35, no. 3, pp. 694–704, 2017. View at Publisher · View at Google Scholar · View at Scopus
  87. D. G. Phinney, “Functional heterogeneity of mesenchymal stem cells: implications for cell therapy,” Journal of Cellular Biochemistry, vol. 113, no. 9, pp. 2806–2812, 2012. View at Publisher · View at Google Scholar · View at Scopus
  88. M. Baddoo, K. Hill, R. Wilkinson et al., “Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection,” Journal of Cellular Biochemistry, vol. 89, no. 6, pp. 1235–1249, 2003. View at Publisher · View at Google Scholar · View at Scopus
  89. N. Tremain, J. Korkko, D. Ibberson, G. C. Kopen, C. DiGirolamo, and D. G. Phinney, “MicroSAGE analysis of 2,353 expressed genes in a single cell-derived colony of undifferentiated human mesenchymal stem cells reveals mRNAs of multiple cell lineages,” Stem Cells, vol. 19, no. 5, pp. 408–418, 2001. View at Publisher · View at Google Scholar · View at Scopus
  90. D. Klein, A. Schmetter, R. Imsak et al., “Therapy with multipotent mesenchymal stromal cells protects lungs from radiation-induced injury and reduces the risk of lung metastasis,” Antioxidants & Redox Signaling, vol. 24, no. 2, pp. 53–69, 2016. View at Publisher · View at Google Scholar · View at Scopus
  91. D. Klein, J. Steens, A. Wiesemann et al., “Mesenchymal stem cell therapy protects lungs from radiation-induced endothelial cell loss by restoring superoxide dismutase 1 expression,” Antioxidants & Redox Signaling, vol. 26, no. 11, pp. 563–582, 2017. View at Publisher · View at Google Scholar · View at Scopus
  92. S. A. Doppler, M.-A. Deutsch, R. Lange, and M. Krane, “Direct reprogramming—the future of cardiac regeneration?” International Journal of Molecular Sciences, vol. 16, no. 8, pp. 17368–17393, 2015. View at Publisher · View at Google Scholar · View at Scopus
  93. P. S. Hou, C. Y. Chuang, C. H. Yeh et al., “Direct conversion of human fibroblasts into neural progenitors using transcription factors enriched in human ESC-derived neural progenitors,” Stem Cell Reports, vol. 8, no. 1, pp. 54–68, 2017. View at Publisher · View at Google Scholar · View at Scopus
  94. D. Nakamori, H. Akamine, K. Takayama, F. Sakurai, and H. Mizuguchi, “Direct conversion of human fibroblasts into hepatocyte-like cells by ATF5, PROX1, FOXA2, FOXA3, and HNF4A transduction,” Scientific Reports, vol. 7, no. 1, article 16675, 2017. View at Publisher · View at Google Scholar · View at Scopus
  95. M. B. Victor, M. Richner, H. E. Olsen et al., “Striatal neurons directly converted from Huntington’s disease patient fibroblasts recapitulate age-associated disease phenotypes,” Nature Neuroscience, vol. 21, no. 3, pp. 341–352, 2018. View at Publisher · View at Google Scholar · View at Scopus
  96. W. Wagner, S. Bork, P. Horn et al., “Aging and replicative senescence have related effects on human stem and progenitor cells,” PLoS One, vol. 4, no. 6, article e5846, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. A. Stolzing, E. Jones, D. McGonagle, and A. Scutt, “Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies,” Mechanisms of Ageing and Development, vol. 129, no. 3, pp. 163–173, 2008. View at Publisher · View at Google Scholar · View at Scopus
  98. Z. Ghosh, K. D. Wilson, Y. Wu, S. Hu, T. Quertermous, and J. C. Wu, “Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells,” PLoS One, vol. 5, no. 2, article e8975, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. M. Stadtfeld, E. Apostolou, H. Akutsu et al., “Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells,” Nature, vol. 465, no. 7295, pp. 175–181, 2010. View at Publisher · View at Google Scholar · View at Scopus
  100. A. Urbach, O. Bar-Nur, G. Q. Daley, and N. Benvenisty, “Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells,” Cell Stem Cell, vol. 6, no. 5, pp. 407–411, 2010. View at Publisher · View at Google Scholar · View at Scopus
  101. S. Hu, M. T. Zhao, F. Jahanbani et al., “Effects of cellular origin on differentiation of human induced pluripotent stem cell-derived endothelial cells,” JCI Insight, vol. 1, no. 8, 2016. View at Publisher · View at Google Scholar