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Stem Cells International
Volume 2012 (2012), Article ID 521343, 9 pages
http://dx.doi.org/10.1155/2012/521343
Review Article

Emerging Stem Cell Therapies: Treatment, Safety, and Biology

Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672

Received 4 May 2012; Revised 3 July 2012; Accepted 4 July 2012

Academic Editor: Erdal Karaöz

Copyright © 2012 Joel Sng and Thomas Lufkin. 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. Martinez Arias and J. M. Brickman, “Gene expression heterogeneities in embryonic stem cell populations: origin and function,” Current Opinion in Cell Biology, vol. 23, no. 6, pp. 650–656, 2011. View at Publisher · View at Google Scholar
  2. A. A. Avilion, S. K. Nicolis, L. H. Pevny, L. Perez, N. Vivian, and R. Lovell-Badge, “Multipotent cell lineages in early mouse development depend on SOX2 function,” Genes and Development, vol. 17, no. 1, pp. 126–140, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Mitsui, Y. Tokuzawa, H. Itoh et al., “The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells,” Cell, vol. 113, no. 5, pp. 631–642, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Masui, Y. Nakatake, Y. Toyooka et al., “Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells,” Nature Cell Biology, vol. 9, no. 6, pp. 625–635, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. J. L. Chew, Y. H. Loh, W. Zhang et al., “Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells,” Molecular and Cellular Biology, vol. 25, no. 14, pp. 6031–6046, 2005. View at Publisher · View at Google Scholar · View at Scopus
  6. Y. Tokuzawa, E. Kaiho, M. Maruyama et al., “Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development,” Molecular and Cellular Biology, vol. 23, no. 8, pp. 2699–2708, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. D. C. Ambrosetti, H. R. Schöler, L. Dailey, and C. Basilico, “Modulation of the activity of multiple transcriptional activation domains by the DNA binding domains mediates the synergistic action of Sox2 and Oct-3 on the fibroblast growth factor-4 enhancer,” The Journal of Biological Chemistry, vol. 275, no. 30, pp. 23387–23397, 2000. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Maruyama, T. Ichisaka, M. Nakagawa, and S. Yamanaka, “Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells,” The Journal of Biological Chemistry, vol. 280, no. 26, pp. 24371–24379, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. D. J. Rodda, J. L. Chew, L. H. Lim et al., “Transcriptional regulation of Nanog by OCT4 and SOX2,” The Journal of Biological Chemistry, vol. 280, no. 26, pp. 24731–24737, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Nishimoto, A. Fukushima, A. Okuda, and M. Muramatsu, “The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2,” Molecular and Cellular Biology, vol. 19, no. 8, pp. 5453–5465, 1999. View at Scopus
  11. Y. Nakatake, N. Fukui, Y. Iwamatsu et al., “Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells,” Molecular and Cellular Biology, vol. 26, no. 20, pp. 7772–7782, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. Y. Miyanari and M. E. Torres-Padilla, “Control of ground-state pluripotency by allelic regulation of Nanog,” Nature, vol. 483, no. 7390, pp. 470–473, 2012. View at Publisher · View at Google Scholar
  13. M. O. Kim, S.-H. Kim, Y.-Y. Cho, et al., “ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4,” Nature Structural & Molecular Biology, vol. 19, no. 3, pp. 283–290, 2012. View at Publisher · View at Google Scholar
  14. E. M. Whitney, A. M. Ghaleb, X. Chen, and V. W. Yang, “Transcriptional profiling of the cell cycle checkpoint gene krüppel-like factor 4 reveals a global inhibitory function in macromolecular biosynthesis,” Gene Expression, vol. 13, no. 2, pp. 85–96, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. X. Chen, E. M. Whitney, S. Y. Gao, and V. W. Yang, “Transcriptional profiling of krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation,” Journal of Molecular Biology, vol. 326, no. 3, pp. 665–677, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. B. D. Rowland, R. Bernards, and D. S. Peeper, “The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene,” Nature Cell Biology, vol. 7, no. 11, pp. 1074–1082, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Wernig, A. Meissner, J. P. Cassady, and R. Jaenisch, “c-Myc is dispensable for direct reprogramming of mouse fibroblasts,” Cell Stem Cell, vol. 2, no. 1, pp. 10–12, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. K. Takahashi and S. Yamanaka, “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors,” Cell, vol. 126, no. 4, pp. 663–676, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. K. Takahashi, K. Tanabe, M. Ohnuki et al., “Induction of pluripotent stem cells from adult human fibroblasts by defined factors,” Cell, vol. 131, no. 5, pp. 861–872, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Yu, M. A. Vodyanik, K. Smuga-Otto et al., “Induced pluripotent stem cell lines derived from human somatic cells,” Science, vol. 318, no. 5858, pp. 1917–1920, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Stadtfeld, K. Brennand, and K. Hochedlinger, “Reprogramming of pancreatic β cells into induced pluripotent stem cells,” Current Biology, vol. 18, no. 12, pp. 890–894, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. D. A. Robinton and G. Q. Daley, “The promise of induced pluripotent stem cells in research and therapy,” Nature, vol. 481, no. 7381, pp. 295–305, 2012. View at Publisher · View at Google Scholar
  23. L. Warren, P. D. Manos, T. Ahfeldt et al., “Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA,” Cell Stem Cell, vol. 7, no. 5, pp. 618–630, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. F. Anokye-Danso, C. M. Trivedi, D. Juhr et al., “Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency,” Cell Stem Cell, vol. 8, no. 4, pp. 376–388, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Kim, A. Doi, B. Wen et al., “Epigenetic memory in induced pluripotent stem cells,” Nature, vol. 467, no. 7313, pp. 285–290, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. O. Bar-Nur, H. A. Russ, S. Efrat, and N. Benvenisty, “Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells,” Cell Stem Cell, vol. 9, no. 1, pp. 17–23, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. R. Lister, M. Pelizzola, Y. S. Kida et al., “Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells,” Nature, vol. 471, no. 7336, pp. 68–73, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. T. T. Onder, N. Kara, A. Cherry, et al., “Chromatin-modifying enzymes as modulators of reprogramming,” Nature, vol. 483, no. 7391, pp. 598–602, 2012. View at Publisher · View at Google Scholar
  29. R. M. Barrett and M. A. Wood, “Beyond transcription factors: the role of chromatin modifying enzymes in regulating transcription required for memory,” Learning and Memory, vol. 15, no. 7, pp. 460–467, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. C. B. Ware, L. Wang, B. H. Mecham et al., “Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells,” Cell Stem Cell, vol. 4, no. 4, pp. 359–369, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. G. Hobley, J. C. McKelvie, J. E. Harmer, et al., “Development of rationally designed DNA N6 adenine methyltransferase inhibitors,” Bioorganic & Medicinal Chemistry Letters, vol. 22, no. 9, pp. 3079–3082, 2012. View at Publisher · View at Google Scholar
  32. B. Feng, J. H. Ng, J. C. D. Heng, and H. H. Ng, “Molecules that promote or enhance reprogramming of somatic cells to induced pluripotent stem cells,” Cell Stem Cell, vol. 4, no. 4, pp. 301–312, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. H. Nakajima, K. Fukazawa, Y. Wakabayashi, et al., “Withania somnifera extract attenuates stem cell factor-stimulated pigmentation in human epidermal equivalents through interruption of ERK phosphorylation within melanocytes,” Journal of Natural Medicines, vol. 66, no. 3, pp. 435–446, 2012. View at Publisher · View at Google Scholar
  34. I. Posner, M. Engel, A. Gazit, and A. Levitzki, “Kinetics of inhibition by tyrphostins of the tyrosine kinase activity of the epidermal growth factor receptor and analysis by a new computer program,” Molecular Pharmacology, vol. 45, no. 4, pp. 673–683, 1994. View at Scopus
  35. A. M. Newman and J. B. Cooper, “Lab-specific gene expression signatures in pluripotent stem cells,” Cell Stem Cell, vol. 7, no. 2, pp. 258–262, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. M. H. Chin, M. J. Mason, W. Xie et al., “Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures,” Cell Stem Cell, vol. 5, no. 1, pp. 111–123, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. D. Bae, P. Mondragon-Teran, D. Hernandez, et al., “Hypoxia enhances the generation of retinal progenitor cells from human induced pluripotent and embryonic stem cells,” Stem Cells and Development, vol. 21, no. 8, pp. 1344–1355, 2012.
  38. Y. Yoshida, K. Takahashi, K. Okita, T. Ichisaka, and S. Yamanaka, “Hypoxia enhances the generation of induced pluripotent stem cells,” Cell Stem Cell, vol. 5, no. 3, pp. 237–241, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. M. E. Bernardo, N. Zaffaroni, F. Novara et al., “Human bone marrow-derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms,” Cancer Research, vol. 67, no. 19, pp. 9142–9149, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. L. A. Meza-Zepeda, A. Noer, J. A. Dahl, F. Micci, O. Myklebost, and P. Collas, “High-resolution analysis of genetic stability of human adipose tissue stem cells cultured to senescence,” Journal of Cellular and Molecular Medicine, vol. 12, no. 2, pp. 553–563, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. U. Ben-David, Y. Mayshar, and N. Benvenisty, “Large-scale analysis reveals acquisition of lineage-specific chromosomal aberrations in human adult stem cells,” Cell Stem Cell, vol. 9, no. 2, pp. 97–102, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. U. Ben-David, N. Benvenisty, and Y. Mayshar, “Genetic instability in human induced pluripotent stem cells: classification of causes and possible safeguards,” Cell Cycle, vol. 9, no. 23, pp. 4603–4604, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. J. Neumann, F. Bahr, D. Horst, et al., “SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer,” BMC Cancer, vol. 11, p. 518, 2011. View at Publisher · View at Google Scholar
  44. O. Leis, A. Eguiara, E. Lopez-Arribillaga et al., “Sox2 expression in breast tumours and activation in breast cancer stem cells,” Oncogene, vol. 31, no. 11, pp. 1354–1365, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. D. E. Linn, X. Yang, F. Sun et al., “A role for OCT4 in tumor initiation of drug-resistant prostate cancer cells,” Genes and Cancer, vol. 1, no. 9, pp. 908–916, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. S. H. Chiou, M. L. Wang, Y. T. Chou et al., “Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation,” Cancer Research, vol. 70, no. 24, pp. 10433–10444, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Gazouli, M. G. Roubelakis, G. E. Theodoropoulos et al., “OCT4 spliced variant OCT4B1 is expressed in human colorectal cancer,” Molecular Carcinogenesis, vol. 51, no. 2, pp. 165–173, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. M. H. Asadi, S. J. Mowla, F. Fathi, A. Aleyasin, J. Asadzadeh, and Y. Atlasi, “OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor,” International Journal of Cancer, vol. 128, no. 11, pp. 2645–2652, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. J. Shan, J. Shen, L. Liu, et al., “Nanog regulates self-renewal of cancer stem cell through IGF pathway in human hepatocellular carcinoma,” Hepatology. In press. View at Publisher · View at Google Scholar
  50. R. Hu, Y. Zuo, L. Zuo et al., “KLF4 expression correlates with the degree of differentiation in colorectal cancer,” Gut and Liver, vol. 5, no. 2, pp. 154–159, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. A. Y. Pandya, L. I. Talley, A. R. Frost et al., “Nuclear localization of KLF4 is associated with an aggressive phenotype in early-stage breast cancer,” Clinical Cancer Research, vol. 10, no. 8, pp. 2709–2719, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. V. Krizhanovsky and S. W. Lowe, “Stem cells: the promises and perils of p53,” Nature, vol. 460, no. 7259, pp. 1085–1086, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. A. I. Caplan, “Mesenchymal stem cells,” Journal of Orthopaedic Research, vol. 9, no. 5, pp. 641–650, 1991. View at Scopus
  54. M. Pevsner-Fischer, S. Levin, and D. Zipori, “The origins of mesenchymal stromal cell heterogeneity,” Stem Cell Reviews and Reports, vol. 7, no. 3, pp. 560–568, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. A. J. Nauta and W. E. Fibbe, “Immunomodulatory properties of mesenchymal stromal cells,” Blood, vol. 110, no. 10, pp. 3499–3506, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. P. S. Knoepfler, “Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine,” Stem Cells, vol. 27, no. 5, pp. 1050–1056, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Wakitani, T. Okabe, S. Horibe et al., “Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months,” Journal of Tissue Engineering and Regenerative Medicine, vol. 5, no. 2, pp. 146–150, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. C. J. Centeno, J. R. Schultz, M. Cheever, et al., “Safety and complications reporting update on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique,” Current Stem Cell Research & Therapy, vol. 6, no. 4, pp. 368–378, 2011.
  59. H. S. Varma, B. Dadarya, and A. Vidyarthi, “The new avenues in the management of osteo-arthritis of knee—stem cells,” Journal of the Indian Medical Association, vol. 108, no. 9, pp. 583–585, 2010. View at Scopus
  60. S. Wakitani, M. Nawata, K. Tensho, T. Okabe, H. Machida, and H. Ohgushi, “Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees,” Journal of Tissue Engineering and Regenerative Medicine, vol. 1, no. 1, pp. 74–79, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. J. M. Hare, J. H. Traverse, T. D. Henry et al., “A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction,” Journal of the American College of Cardiology, vol. 54, no. 24, pp. 2277–2286, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. P. Macchiarini, P. Jungebluth, T. Go et al., “Clinical transplantation of a tissue-engineered airway,” The Lancet, vol. 372, no. 9655, pp. 2023–2030, 2008. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Baiguera, P. Jungebluth, A. Burns et al., “Tissue engineered human tracheas for in vivo implantation,” Biomaterials, vol. 31, no. 34, pp. 8931–8938, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. J. Tan, W. Wu, X. Xu, et al., “Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial,” The Journal of the American Medical Association, vol. 307, no. 11, pp. 1169–1177, 2012. View at Publisher · View at Google Scholar
  65. 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
  66. R. Jiang, Z. Han, G. Zhuo, et al., “Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study,” Frontiers of Medicine, vol. 5, no. 1, pp. 94–100, 2011. View at Publisher · View at Google Scholar
  67. C. Siatskas, N. L. Payne, M. A. Short, et al., “A consensus statement addressing mesenchymal stem cell transplantation for multiple sclerosis: it's time!,” Stem Cell Reviews and Reports, vol. 6, no. 4, pp. 500–506, 2010. View at Publisher · View at Google Scholar
  68. J. S. Lee, J. M. Hong, G. J. Moon, P. H. Lee, Y. H. Ahn, and O. Y. Bang, “A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke,” Stem Cells, vol. 28, no. 6, pp. 1099–1106, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. Y. Zhang, D. Khan, J. Delling, et al., “Mechanisms underlying the osteo- and adipo-differentiation of human mesenchymal stem cells,” The Scientific World Journal, vol. 2012, Article ID 793823, 14 pages, 2012. View at Publisher · View at Google Scholar
  70. J. Pak, “Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series,” Journal of Medical Case Reports, vol. 5, p. 296, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. S. Schreml, P. Babilas, S. Fruth et al., “Harvesting human adipose tissue-derived adult stem cells: resection versus liposuction,” Cytotherapy, vol. 11, no. 7, pp. 947–957, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. S. G. Dubois, E. Z. Floyd, S. Zvonic et al., “Isolation of human adipose-derived stem cells from biopsies and liposuction specimens,” Methods in Molecular Biology, vol. 449, pp. 69–79, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. N. Koyama, Y. Okubo, K. Nakao, et al., “Pluripotency of mesenchymal cells derived from synovial fluid in patients with temporomandibular joint disorder,” Life Sciences, vol. 89, no. 19–20, pp. 741–747, 2011.
  74. T. Miyamoto, T. Muneta, T. Tabuchi et al., “Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits,” Arthritis Research & Therapy, vol. 12, no. 6, article R206, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. Y. Sakaguchi, I. Sekiya, K. Yagishita, and T. Muneta, “Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source,” Arthritis and Rheumatism, vol. 52, no. 8, pp. 2521–2529, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. Y. J. Ju, T. Muneta, H. Yoshimura, H. Koga, and I. Sekiya, “Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing,” Cell and Tissue Research, vol. 332, no. 3, pp. 469–478, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. I. Sekiya, T. Muneta, H. Koga, et al., “Articular cartilage regeneration with synovial mesenchymal stem cells,” Clinical Calcium, vol. 21, no. 6, pp. 879–889, 2011.
  78. W. Ando, K. Tateishi, D. Katakai et al., “In vitro generation of a scaffold-free tissue-engineered construct (TEC) derived from human synovial mesenchymal stem cells: biological and mechanical properties and further chondrogenic potential,” Tissue Engineering A, vol. 14, no. 12, pp. 2041–2049, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. D. A. De Ugarte, Z. Alfonso, P. A. Zuk et al., “Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow,” Immunology Letters, vol. 89, no. 2-3, pp. 267–270, 2003. View at Publisher · View at Google Scholar · View at Scopus
  80. J. I. Huang, N. Kazmi, M. M. Durbhakula, T. M. Hering, J. U. Yoo, and B. Johnstone, “Chondrogenic potential of progenitor cells derived from human bone marrow and adipose tissue: a patient-matched comparison,” Journal of Orthopaedic Research, vol. 23, no. 6, pp. 1383–1389, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. J. Yang, T. Song, P. Wu, et al., “Differentiation potential of human mesenchymal stem cells derived from adipose tissue and bone marrow to sinus node-like cells,” Molecular Medicine Reports, vol. 5, no. 1, pp. 108–113, 2012.
  82. E. D. Thomas, H. L. Lochte, W. C. Lu, and J. W. Ferrebee, “Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy,” The New England Journal of Medicine, vol. 257, no. 11, pp. 491–496, 1957. View at Scopus
  83. C. E. Müller-Sieburg, R. H. Cho, M. Thoman, B. Adkins, and H. B. Sieburg, “Deterministic regulation of hematopoietic stem cell self-renewal and differentiation,” Blood, vol. 100, no. 4, pp. 1302–1309, 2002. View at Scopus
  84. L. Rossi, G. A. Challen, O. Sirin, et al., “Hematopoietic stem cell characterization and isolation,” Methods in Molecular Biology, vol. 750, part 2, pp. 47–59, 2011. View at Publisher · View at Google Scholar
  85. T. Ishida, M. Hishizawa, K. Kato, et al., “Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study,” Blood. In press. View at Publisher · View at Google Scholar
  86. J. P. Fermand, P. Ravaud, S. Chevret et al., “High-dose therapy and autologous blood stem cell transplantation in multiple myeloma: preliminary results of a randomized trial involving 167 patients,” Stem Cells, vol. 13, supplement 2, pp. 156–159, 1995. View at Scopus
  87. H. M. Lokhorst, P. Sonneveld, J. J. Cornelissen et al., “Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma,” Bone Marrow Transplantation, vol. 23, no. 4, pp. 317–322, 1999. View at Scopus
  88. P. L. McCarthy, K. Owzar, C. C. Hofmeister, et al., “Lenalidomide after stem-cell transplantation for multiple myeloma,” The New England Journal of Medicine, vol. 366, no. 19, pp. 1770–1781, 2012. View at Publisher · View at Google Scholar
  89. M. Attal, V. Lauwers-Cances, G. Marit, et al., “Lenalidomide maintenance after stem-cell transplantation for multiple myeloma,” The New England Journal of Medicine, vol. 366, no. 19, pp. 1782–1791, 2012. View at Publisher · View at Google Scholar
  90. A. J. Jakubowiak, K. A. Griffith, D. E. Reece et al., “Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial,” Blood, vol. 118, no. 3, pp. 535–543, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. A. J. Jakubowiak, T. Kendall, A. Al-Zoubi et al., “Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma,” Journal of Clinical Oncology, vol. 27, no. 30, pp. 5015–5022, 2009. View at Publisher · View at Google Scholar · View at Scopus
  92. J. S. Miller, E. H. Warren, M. R. M. van den Brink et al., “NCI first international workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: report from the committee on the biology underlying recurrence of malignant disease following allogeneic HSCT: graft-versus-tumor/leukemia reaction,” Biology of Blood and Marrow Transplantation, vol. 16, no. 5, pp. 565–586, 2010. View at Publisher · View at Google Scholar · View at Scopus
  93. A. Utsunomiya, Y. Miyazaki, Y. Takatsuka et al., “Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation,” Bone Marrow Transplantation, vol. 27, no. 1, pp. 15–20, 2001. View at Publisher · View at Google Scholar · View at Scopus
  94. W. Hasegawa, G. R. Pond, J. T. Rifkind et al., “Long-term follow-up of secondary malignancies in adults after allogeneic bone marrow transplantation,” Bone Marrow Transplantation, vol. 35, no. 1, pp. 51–55, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. H. J. Deeg, J. Sanders, and P. Martin, “Secondary malignancies after marrow transplantation,” Experimental Hematology, vol. 12, no. 8, pp. 660–666, 1984. View at Scopus
  96. R. F. Wynn, J. E. Wraith, J. Mercer et al., “Improved metabolic correction in patients with lysosomal storage disease treated with hematopoietic stem cell transplant compared with enzyme replacement therapy,” Journal of Pediatrics, vol. 154, no. 4, pp. 609–611, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. H. Church, K. Tylee, A. Cooper et al., “Biochemical monitoring after haemopoietic stem cell transplant for Hurler syndrome (MPSIH): implications for functional outcome after transplant in metabolic disease,” Bone Marrow Transplantation, vol. 39, no. 4, pp. 207–210, 2007. View at Publisher · View at Google Scholar · View at Scopus
  98. E. Shapiro, W. Krivit, L. Lockman et al., “Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy,” The Lancet, vol. 356, no. 9231, pp. 713–718, 2000. View at Scopus
  99. J. Cohen, “The emerging race to cure HIV infections,” Science, vol. 332, no. 6031, pp. 784–789, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. J. Yang, Y. Yan, B. Ciric et al., “Evaluation of bone marrow- and brain-derived neural stem cells in therapy of central nervous system autoimmunity,” The American Journal of Pathology, vol. 177, no. 4, pp. 1989–2001, 2010. View at Publisher · View at Google Scholar · View at Scopus
  101. B. A. Reynolds and S. Weiss, “Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system,” Science, vol. 255, no. 5052, pp. 1707–1710, 1992. View at Scopus
  102. S. Nemati, M. Hatami, S. Kiani et al., “Long-term self-renewable feeder-free human induced pluripotent stem cell-derived neural progenitors,” Stem Cells and Development, vol. 20, no. 3, pp. 503–514, 2011. View at Publisher · View at Google Scholar · View at Scopus
  103. A. Falk, P. Koch, J. Kesavan, et al., “Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons,” PLoS One, vol. 7, no. 1, Article ID e29597, 2012.
  104. J. B. Kim, B. Greber, M. J. Arazo-Bravo et al., “Direct reprogramming of human neural stem cells by OCT4,” Nature, vol. 461, no. 7264, pp. 649–653, 2009. View at Publisher · View at Google Scholar · View at Scopus
  105. C. Varela, J. A. Denis, J. Polentes, et al., “Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells,” The Journal of Clinical Investigation, vol. 122, no. 2, pp. 569–574, 2012. View at Publisher · View at Google Scholar
  106. N. J. Harrison, “Genetic instability in neural stem cells: an inconvenient truth?” The Journal of Clinical Investigation, vol. 122, no. 2, pp. 484–486, 2012. View at Publisher · View at Google Scholar
  107. S. Pluchino, A. Quattrini, E. Brambilla et al., “Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis,” Nature, vol. 422, no. 6933, pp. 688–694, 2003. View at Publisher · View at Google Scholar · View at Scopus
  108. S. Pluchino, L. Zanotti, B. Rossi et al., “Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism,” Nature, vol. 436, no. 7048, pp. 266–271, 2005. View at Publisher · View at Google Scholar · View at Scopus
  109. M. Neri, A. Ricca, I. di Girolamo, et al., “Neural stem cell gene therapy ameliorates pathology and function in a mouse model of globoid cell leukodystrophy,” Stem Cells, vol. 29, no. 10, pp. 1559–1571, 2011. View at Publisher · View at Google Scholar
  110. M. Aharonowiz, O. Einstein, N. Fainstein, H. Lassmann, B. Reubinoff, and T. Ben-Hur, “Neuroprotective effect of transplanted human embryonic stem cell-derived neural precursors in an animal model of multiple sclerosis,” PLoS ONE, vol. 3, no. 9, Article ID e3145, 2008. View at Publisher · View at Google Scholar · View at Scopus
  111. S. Pluchino, L. Zanotti, E. Brambilla et al., “Immune regulatory neural stem/precursor cells protect from central nervous system autoimmunity by restraining dendritic cell function,” PLoS ONE, vol. 4, no. 6, Article ID e5959, 2009. View at Publisher · View at Google Scholar · View at Scopus
  112. J. Yang, Z. Jiang, D. C. Fitzgerald et al., “Adult neural stem cells expressing IL-10 confer potent immunomodulation and remyelination in experimental autoimmune encephalitis,” The Journal of Clinical Investigation, vol. 119, no. 12, pp. 3678–3691, 2009. View at Publisher · View at Google Scholar · View at Scopus
  113. F. H. Gage, “Mammalian neural stem cells,” Science, vol. 287, no. 5457, pp. 1433–1438, 2000. View at Publisher · View at Google Scholar · View at Scopus
  114. A. I. Danilov, R. Covacu, M. C. Moe et al., “Neurogenesis in the adult spinal cord in an experimental model of multiple sclerosis,” European Journal of Neuroscience, vol. 23, no. 2, pp. 394–400, 2006. View at Publisher · View at Google Scholar · View at Scopus
  115. L. Brundin, H. Brismar, A. I. Danilov, T. Olsson, and C. B. Johansson, “Neural stem cells: a potential source for remyelination in neuroinflammatory disease,” Brain Pathology, vol. 13, no. 3, pp. 322–328, 2003. View at Scopus
  116. C. B. Johansson, S. Momma, D. L. Clarke, M. Risling, U. Lendahl, and J. Frisén, “Identification of a neural stem cell in the adult mammalian central nervous system,” Cell, vol. 96, no. 1, pp. 25–34, 1999. View at Publisher · View at Google Scholar · View at Scopus
  117. B. Saha, M. Jaber, and A. Gaillard, “Potentials of endogenous neural stem cells in cortical repair,” Frontiers in Cellular Neuroscience, vol. 6, p. 14, 2012.
  118. T. Shirasaka, W. Ukai, T. Yoshinaga, et al., “Promising therapy of neural stem cell transplantation for FASD model—neural network reconstruction and behavior recovery,” Nihon Arukoru Yakubutsu Igakkai Zasshi, vol. 46, no. 6, pp. 576–584, 2011.
  119. L. S. Shihabuddin and S. H. Cheng, “Neural stem cell transplantation as a therapeutic approach for treating lysosomal storage diseases,” Neurotherapeutics, vol. 8, no. 4, pp. 659–667, 2011. View at Publisher · View at Google Scholar
  120. G. Chen, Y. R. Hu, H. Wan et al., “Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells and Schwann cells,” Chinese Medical Journal, vol. 123, no. 17, pp. 2424–2431, 2010. View at Scopus
  121. M. Shackleton, F. Vaillant, K. J. Simpson et al., “Generation of a functional mammary gland from a single stem cell,” Nature, vol. 439, no. 7072, pp. 84–88, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. J. Stingl, P. Eirew, I. Ricketson et al., “Purification and unique properties of mammary epithelial stem cells,” Nature, vol. 439, no. 7079, pp. 993–997, 2006. View at Publisher · View at Google Scholar · View at Scopus
  123. D. Dey, M. Saxena, A. N. Paranjape et al., “Phenotypic and functional characterization of human mammary stem/progenitor cells in long term culture,” PLoS ONE, vol. 4, no. 4, Article ID e5329, 2009. View at Publisher · View at Google Scholar · View at Scopus
  124. C. M. Dekaney, J. J. Fong, R. J. Rigby, P. K. Lund, S. J. Henning, and M. A. Helmrath, “Expansion of intestinal stem cells associated with long-term adaptation following ileocecal resection in mice,” American Journal of Physiology, vol. 293, no. 5, pp. G1013–G1022, 2007. View at Publisher · View at Google Scholar · View at Scopus
  125. I. Breuskin, M. Bodson, N. Thelen et al., “Strategies to regenerate hair cells: identification of progenitors and critical genes,” Hearing Research, vol. 236, no. 1-2, pp. 1–10, 2008. View at Publisher · View at Google Scholar · View at Scopus
  126. H. Li, H. Liu, and S. Heller, “Pluripotent stem cells from the adult mouse inner ear,” Nature Medicine, vol. 9, no. 10, pp. 1293–1299, 2003. View at Publisher · View at Google Scholar · View at Scopus
  127. I. Dobrinski, “Germ cell transplantation and testis tissue xenografting in domestic animals,” Animal Reproduction Science, vol. 89, no. 1–4, pp. 137–145, 2005. View at Publisher · View at Google Scholar · View at Scopus
  128. A. Honaramooz, E. Behboodi, S. O. Megee et al., “Fertility and germline transmission of donor haplotype following germ cell transplantation in immunocompetent goats,” Biology of Reproduction, vol. 69, no. 4, pp. 1260–1264, 2003. View at Publisher · View at Google Scholar · View at Scopus
  129. R. L. Brinster and M. R. Avarbock, “Germline transmission of donor haplotype following spermatogonial transplantation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 24, pp. 11303–11307, 1994. View at Publisher · View at Google Scholar · View at Scopus
  130. M. Tesio, K. Golan, S. Corso et al., “Enhanced c-Met activity promotes G-CSF-induced mobilization of hematopoietic progenitor cells via ROS signaling,” Blood, vol. 117, no. 2, pp. 419–428, 2011. View at Publisher · View at Google Scholar · View at Scopus