1932

Abstract

Two opposing descriptions of so-called mesenchymal stem cells (MSCs) exist at this time. One sees MSCs as the postnatal, self-renewing, and multipotent stem cells for the skeleton. This cell coincides with a specific type of bone marrow perivascular cell. In skeletal physiology, this skeletal stem cell is pivotal to the growth and lifelong turnover of bone and to its native regeneration capacity. In hematopoietic physiology, its role as a key player in maintaining hematopoietic stem cells in their niche and in regulating the hematopoietic microenvironment is emerging. In the alternative description, MSCs are ubiquitous in connective tissues and are defined by in vitro characteristics and by their use in therapy, which rests on their ability to modulate the function of host tissues rather than on stem cell properties. Here, I discuss how the two views developed, conceptually and experimentally, and attempt to clarify the confusion arising from their collision.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cellbio-100913-013132
2014-10-06
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/cellbio/30/1/annurev-cellbio-100913-013132.html?itemId=/content/journals/10.1146/annurev-cellbio-100913-013132&mimeType=html&fmt=ahah

Literature Cited

  1. Akiyama K, Chen C, Wang D, Xu X, Qu C. et al. 2012. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell 10:544–55 [Google Scholar]
  2. Arai F, Ohneda O, Miyamoto T, Zhang XQ, Suda T. 2002. Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation. J. Exp. Med. 195:1549–63 [Google Scholar]
  3. Armulik A, Genove G, Betsholtz C. 2011. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev. Cell 21:193–215 [Google Scholar]
  4. Au P, Tam J, Fukumura D, Jain RK. 2008. Bone marrow-derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature. Blood 111:4551–58 [Google Scholar]
  5. Badillo AT, Peranteau WH, Heaton TE, Quinn C, Flake AW. 2008. Murine bone marrow derived stromal progenitor cells fail to prevent or treat acute graft-versus-host disease. Br. J. Haematol. 141:224–34 [Google Scholar]
  6. Barry FP, Boynton RE, Haynesworth S, Murphy JM, Zaia J. 1999. The monoclonal antibody SH-2, raised against human mesenchymal stem cells, recognizes an epitope on endoglin (CD105). Biochem. Biophys. Res. Commun. 265:134–39 [Google Scholar]
  7. Beggs KJ, Lyubimov A, Borneman JN, Bartholomew A, Moseley A. et al. 2006. Immunologic consequences of multiple, high-dose administration of allogeneic mesenchymal stem cells to baboons. Cell Transplant. 15:711–21 [Google Scholar]
  8. Bennett JH, Joyner CJ, Triffitt JT, Owen ME. 1991. Adipocytic cells cultured from marrow have osteogenic potential. J. Cell Sci. 99:Pt. 1131–39 [Google Scholar]
  9. Beresford JN, Bennett JH, Devlin C, Leboy PS, Owen ME. 1992. Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J. Cell Sci. 102:Pt. 2341–51 [Google Scholar]
  10. Bernardo ME, Fibbe WE. 2013. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell 13:392–402 [Google Scholar]
  11. Bianco P. 2011. Bone and the hematopoietic niche: a tale of two stem cells. Blood 117:5281–88 [Google Scholar]
  12. Bianco P. 2013. Don't market stem-cell products ahead of proof. Nature 499:255 [Google Scholar]
  13. Bianco P, Barker R, Brustle O, Cattaneo E, Clevers H. et al. 2013a. Regulation of stem cell therapies under attack in Europe: for whom the bell tolls. EMBO J. 32:1489–95 [Google Scholar]
  14. Bianco P, Bonucci E. 1991. Endosteal surfaces in hyperparathyroidism: an enzyme cytochemical study on low-temperature-processed, glycol-methacrylate-embedded bone biopsies. Virchows Arch. A Pathol. Anat. 419:425–31 [Google Scholar]
  15. Bianco P, Boyde A. 1993. Confocal images of marrow stromal (Westen-Bainton) cells. Histochemistry 100:93–99 [Google Scholar]
  16. Bianco P, Bradbeer JN, Riminucci M, Boyde A. 1993a. Marrow stromal (Western-Bainton) cells: identification, morphometry, confocal imaging and changes in disease. Bone 14:315–20 [Google Scholar]
  17. Bianco P, Cao X, Frenette PS, Mao JJ, Robey PG. et al. 2013b. The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat. Med. 19:35–42 [Google Scholar]
  18. Bianco P, Costantini M, Dearden LC, Bonucci E. 1988. Alkaline phosphatase positive precursors of adipocytes in the human bone marrow. Br. J. Haematol. 68:401–3 [Google Scholar]
  19. Bianco P, Gehron Robey P. 2000. Marrow stromal stem cells. J. Clin. Investig. 105:1663–68 [Google Scholar]
  20. Bianco P, Kuznetsov SA, Riminucci M, Fisher LW, Spiegel AM, Robey PG. 1998. Reproduction of human fibrous dysplasia of bone in immunocompromised mice by transplanted mosaics of normal and Gsalpha-mutated skeletal progenitor cells. J. Clin. Investig. 101:1737–44 [Google Scholar]
  21. Bianco P, Kuznetsov SA, Riminucci M, Gehron Robey P. 2006. Postnatal skeletal stem cells. Methods Enzymol. 419:117–48 [Google Scholar]
  22. Bianco P, Riminucci M, Bonucci E, Termine JD, Robey PG. 1993b. Bone sialoprotein (BSP) secretion and osteoblast differentiation: relationship to bromodeoxyuridine incorporation, alkaline phosphatase, and matrix deposition. J. Histochem. Cytochem. 41:183–91 [Google Scholar]
  23. Bianco P, Riminucci M, Gronthos S, Robey PG. 2001. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19:180–92 [Google Scholar]
  24. Bianco P, Robey PG. 2001. Stem cells in tissue engineering. Nature 414:118–21 [Google Scholar]
  25. Bianco P, Robey PG. 2004. Skeletal stem cells. Handbook of Adult and Fetal Stem Cells RP Lanza 415–24 San Diego: Academic [Google Scholar]
  26. Bianco P, Robey PG, Simmons PJ. 2008. Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2:313–19 [Google Scholar]
  27. Brockes JP, Kumar A. 2005. Appendage regeneration in adult vertebrates and implications for regenerative medicine. Science 310:1919–23 [Google Scholar]
  28. Brown-Sequard CE. 1889. The effects produced on man by subcutaneous injection of a liquid obtained from the testicles of animals. Lancet 137:105–7 [Google Scholar]
  29. Bryder D, Rossi DJ, Weissman IL. 2006. Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am. J. Pathol. 169:338–46 [Google Scholar]
  30. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP. et al. 2003. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–46 [Google Scholar]
  31. Caplan AI. 1991. Mesenchymal stem cells. J. Orthop. Res. 9:641–50 [Google Scholar]
  32. Caplan AI. 1994. The mesengenic process. Clin. Plast. Surg. 21:429–35 [Google Scholar]
  33. Caplan AI. 2008. All MSCs are pericytes?. Cell Stem Cell 3:229–30 [Google Scholar]
  34. Caplan AI, Correa D. 2011. The MSC: an injury drugstore. Cell Stem Cell 9:11–15 [Google Scholar]
  35. Castro-Malaspina H, Gay RE, Resnick G, Kapoor N, Meyers P. et al. 1980. Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny. Blood 56:289–301 [Google Scholar]
  36. Cattoretti G, Schiro R, Orazi A, Soligo D, Colombo MP. 1993. Bone marrow stroma in humans: anti-nerve growth factor receptor antibodies selectively stain reticular cells in vivo and in vitro. Blood 81:1726–38 [Google Scholar]
  37. Chamberlain JR, Schwarze U, Wang PR, Hirata RK, Hankenson KD. et al. 2004. Gene targeting in stem cells from individuals with osteogenesis imperfecta. Science 303:1198–201 [Google Scholar]
  38. Chan CK, Chen CC, Luppen CA, Kim JB, DeBoer AT. et al. 2009. Endochondral ossification is required for haematopoietic stem-cell niche formation. Nature 457:490–94 [Google Scholar]
  39. Chan CK, Lindau P, Jiang W, Chen JY, Zhang LF. et al. 2013. Clonal precursor of bone, cartilage, and hematopoietic niche stromal cells. Proc. Natl. Acad. Sci. USA 110:12643–48 [Google Scholar]
  40. Chatterjea A, LaPointe VL, Alblas J, Chatterjea S, van Blitterswijk CA, de Boer J. 2014. Suppression of the immune system as a critical step for bone formation from allogeneic osteoprogenitors implanted in rats. J. Cell. Mol. Med. 18:134–42 [Google Scholar]
  41. Chinnadurai R, Copland IB, Patel SR, Galipeau J. 2014. IDO-independent suppression of T cell effector function by IFN-γ-licensed human mesenchymal stromal cells. J. Immunol. 192:1491–501 [Google Scholar]
  42. Chou DB, Sworder B, Bouladoux N, Roy CN, Uchida AM. et al. 2012. Stromal-derived IL-6 alters the balance of myeloerythroid progenitors during Toxoplasma gondii infection. J. Leukoc. Biol. 92:123–31 [Google Scholar]
  43. Colter DC, Sekiya I, Prockop DJ. 2001. Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc. Natl. Acad. Sci. USA 98:7841–45 [Google Scholar]
  44. Conrad JC. 2012. Quantifying collective behavior in mammalian cells. Proc. Natl. Acad. Sci. USA 109:7591–92 [Google Scholar]
  45. Crisan M, Yap S, Casteilla L, Chen CW, Corselli M. et al. 2008. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–13 [Google Scholar]
  46. da Silva Meirelles L, Caplan AI, Nardi NB. 2008. In search of the in vivo identity of mesenchymal stem cells. Stem Cells 26:2287–99 [Google Scholar]
  47. da Silva Meirelles L, Chagastelles PC, Nardi NB. 2006. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J. Cell Sci. 119:2204–13 [Google Scholar]
  48. Dazzi F, Marelli-Berg FM. 2008. Mesenchymal stem cells for graft-versus-host disease: close encounters with T cells. Eur. J. Immunol. 38:1479–82 [Google Scholar]
  49. Deguchi K, Yagi H, Inada M, Yoshizaki K, Kishimoto T, Komori T. 1999. Excessive extramedullary hematopoiesis in Cbfa1-deficient mice with a congenital lack of bone marrow. Biochem. Biophys. Res. Commun. 255:352–59 [Google Scholar]
  50. Dellavalle A, Sampaolesi M, Tonlorenzi R, Tagliafico E, Sacchetti B. et al. 2007. Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat. Cell Biol. 9:255–67 [Google Scholar]
  51. Deschaseaux F, Charbord P. 2000. Human marrow stromal precursors are α1 integrin subunit-positive. J. Cell. Physiol. 184:319–25 [Google Scholar]
  52. Dezawa M, Ishikawa H, Itokazu Y, Yoshihara T, Hoshino M. et al. 2005. Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science 309:314–17 [Google Scholar]
  53. Díaz-Flores L, Gutiérrez R, Madrid JF, Varela H, Valladares F. et al. 2009. Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. Histol. Histopathol. 24:909–69 [Google Scholar]
  54. Ding L, Morrison SJ. 2013. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature 495:231–35 [Google Scholar]
  55. Ding L, Saunders TL, Enikolopov G, Morrison SJ. 2012. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481:457–62 [Google Scholar]
  56. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F. et al. 2006. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–17 [Google Scholar]
  57. Dominici M, Paolucci P, Conte P, Horwitz EM. 2009. Heterogeneity of multipotent mesenchymal stromal cells: from stromal cells to stem cells and vice versa. Transplantation 87:S36–42 [Google Scholar]
  58. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. 1997. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747–54 [Google Scholar]
  59. Eliopoulos N, Stagg J, Lejeune L, Pommey S, Galipeau J. 2005. Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood 106:4057–65 [Google Scholar]
  60. Esner M, Meilhac SM, Relaix F, Nicolas JF, Cossu G, Buckingham ME. 2006. Smooth muscle of the dorsal aorta shares a common clonal origin with skeletal muscle of the myotome. Development 133:737–49 [Google Scholar]
  61. Fan Z, Yamaza T, Lee JS, Yu J, Wang S. et al. 2009. BCOR regulates mesenchymal stem cell function by epigenetic mechanisms. Nat. Cell Biol. 11:1002–9 [Google Scholar]
  62. Filshie RJ, Zannettino AC, Makrynikola V, Gronthos S, Henniker AJ. et al. 1998. MUC18, a member of the immunoglobulin superfamily, is expressed on bone marrow fibroblasts and a subset of hematological malignancies. Leukemia 12:414–21 [Google Scholar]
  63. Friedenstein A, Kuralesova AI. 1971. Osteogenic precursor cells of bone marrow in radiation chimeras. Transplantation 12:99–108 [Google Scholar]
  64. Friedenstein AJ. 1961. Osteogenetic activity of transplanted transitional epithelium. Acta Anat. 45:31–59 [Google Scholar]
  65. Friedenstein AJ. 1962. Humoral nature of osteogenic activity of transitional epithelium. Nature 194:698–99 [Google Scholar]
  66. Friedenstein AJ. 1976. Precursor cells of mechanocytes. Int. Rev. Cytol. 47:327–59 [Google Scholar]
  67. Friedenstein AJ. 1980. Stromal mechanisms of bone marrow: cloning in vitro and retransplantation in vivo. Haematol. Blood Transfus. 25:19–29 [Google Scholar]
  68. Friedenstein AJ. 1990. Bone marrow osteogenic stem cells. Calcium Regulation and Bone Metabolism DV Cohn, FH Glorieux, TJ Martin 353–61 Amsterdam: Elsevier Sci [Google Scholar]
  69. Friedenstein AJ. 1995. Marrow stromal fibroblasts. Calcif. Tissue Int. 56:Suppl. 1S17 [Google Scholar]
  70. Friedenstein AJ, Chailakhjan RK, Lalykina KS. 1970. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 3:393–403 [Google Scholar]
  71. Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF. et al. 1974. Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp. Hematol. 2:83–92 [Google Scholar]
  72. Friedenstein AJ, Gorskaja JF, Kulagina NN. 1976. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp. Hematol. 4:267–74 [Google Scholar]
  73. Friedenstein AJ, Latzinik NW, Grosheva AG, Gorskaya UF. 1982. Marrow microenvironment transfer by heterotopic transplantation of freshly isolated and cultured cells in porous sponges. Exp. Hematol. 10:217–27 [Google Scholar]
  74. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. 1968. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–47 [Google Scholar]
  75. Friedenstein AJ, Piatetzky S II, Petrakova KV. 1966. Osteogenesis in transplants of bone marrow cells. J. Embryol. Exp. Morphol. 16:381–90 [Google Scholar]
  76. Galmiche MC, Koteliansky VE, Briere J, Herve P, Charbord P. 1993. Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway. Blood 82:66–76 [Google Scholar]
  77. Gang EJ, Bosnakovski D, Figueiredo CA, Visser JW, Perlingeiro RC. 2007. SSEA-4 identifies mesenchymal stem cells from bone marrow. Blood 109:1743–51 [Google Scholar]
  78. Gholamrezanezhad A, Mirpour S, Bagheri M, Mohamadnejad M, Alimoghaddam K. et al. 2011. In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis. Nucl. Med. Biol. 38:961–67 [Google Scholar]
  79. Goldstein S. 1990. Replicative senescence: The human fibroblast comes of age. Science 249:1129–33 [Google Scholar]
  80. Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ. et al. 2013. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 495:227–30 [Google Scholar]
  81. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. 2000. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl. Acad. Sci. USA 97:13625–30 [Google Scholar]
  82. Hall BK, Miyake T. 1992. The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis. Anat. Embryol. 186:107–24 [Google Scholar]
  83. Hall BK, Miyake T. 1995. Divide, accumulate, differentiate: cell condensation in skeletal development revisited. Int. J. Dev. Biol. 39:881–93 [Google Scholar]
  84. Hayflick L, Moorhead PS. 1961. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25:585–621 [Google Scholar]
  85. Holmbeck K, Bianco P, Caterina J, Yamada S, Kromer M. et al. 1999. MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99:81–92 [Google Scholar]
  86. Holmbeck K, Bianco P, Chrysovergis K, Yamada S, Birkedal-Hansen H. 2003. MT1-MMP-dependent, apoptotic remodeling of unmineralized cartilage: a critical process in skeletal growth. J. Cell Biol. 163:661–71 [Google Scholar]
  87. Hori S. 2011. Stability of regulatory T-cell lineage. Adv. Immunol. 112:1–24 [Google Scholar]
  88. Horwitz EM. Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I. , Le et al. 2005. Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy 7:393–95 [Google Scholar]
  89. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL. et al. 1999. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat. Med. 5:309–13 [Google Scholar]
  90. Jain RK. 2003. Molecular regulation of vessel maturation. Nat. Med. 9:685–93 [Google Scholar]
  91. Jeon MS, Lim HJ, Yi TG, Im MW, Yoo HS. et al. 2010. Xenoreactivity of human clonal mesenchymal stem cells in a major histocompatibility complex-matched allogeneic graft-versus-host disease mouse model. Cell. Immunol. 261:57–63 [Google Scholar]
  92. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD. et al. 2002. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49 [Google Scholar]
  93. Johnson K, Zhu S, Tremblay MS, Payette JN, Wang J. et al. 2012. A stem cell-based approach to cartilage repair. Science 336:717–21 [Google Scholar]
  94. Jones S, Horwood N, Cope A, Dazzi F. 2007. The antiproliferative effect of mesenchymal stem cells is a fundamental property shared by all stromal cells. J. Immunol. 179:2824–31 [Google Scholar]
  95. Kaipe H, Erkers T, Sadeghi B, Ringdén O. 2014. Stromal cells—are they really useful for GVHD?. Bone Marrow Transpl. 49:737–43 [Google Scholar]
  96. Karadag A, Riminucci M, Bianco P, Cherman N, Kuznetsov SA. et al. 2004. A novel technique based on a PNA hybridization probe and FRET principle for quantification of mutant genotype in fibrous dysplasia/McCune-Albright syndrome. Nucleic Acids Res. 32:e63 [Google Scholar]
  97. Karp JM, Leng Teo GS. 2009. Mesenchymal stem cell homing: The devil is in the details. Cell Stem Cell 4:206–16 [Google Scholar]
  98. Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N. et al. 1994. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J. Cell Biol. 127:1755–66 [Google Scholar]
  99. Keating A. 2012. Mesenchymal stromal cells: new directions. Cell Stem Cell 10:709–16 [Google Scholar]
  100. Keating A, Whalen CK, Singer JW. 1983. Cultured marrow stromal cells express common acute lymphoblastic leukaemia antigen (CALLA): implications for marrow transplantation. Br. J. Haematol. 55:623–28 [Google Scholar]
  101. Kiel MJ, Morrison SJ. 2006. Maintaining hematopoietic stem cells in the vascular niche. Immunity 25:862–64 [Google Scholar]
  102. Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ. 2005. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121:1109–21 [Google Scholar]
  103. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K. et al. 1997. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–64 [Google Scholar]
  104. Kon E, Muraglia A, Corsi A, Bianco P, Marcacci M. et al. 2000. Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J. Biomed. Mater. Res. 49:328–37 [Google Scholar]
  105. Kopen GC, Prockop DJ, Phinney DG. 1999. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc. Natl. Acad. Sci. USA 96:10711–16 [Google Scholar]
  106. Krebsbach PH, Kuznetsov SA, Satomura K, Emmons RV, Rowe DW, Robey PG. 1997. Bone formation in vivo: comparison of osteogenesis by transplanted mouse and human marrow stromal fibroblasts. Transplantation 63:1059–69 [Google Scholar]
  107. Kuznetsov SA, Cherman N, Riminucci M, Collins MT, Robey PG, Bianco P. 2008. Age-dependent demise of GNAS-mutated skeletal stem cells and “normalization” of fibrous dysplasia of bone. J. Bone Miner. Res. 23:1731–40 [Google Scholar]
  108. Kuznetsov SA, Krebsbach PH, Satomura K, Kerr J, Riminucci M. et al. 1997. Single-colony derived strains of human marrow stromal fibroblasts form bone after transplantation in vivo. J. Bone Miner. Res. 12:1335–47 [Google Scholar]
  109. Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG. 2001. Circulating skeletal stem cells. J. Cell Biol. 153:1133–40 [Google Scholar]
  110. Kuznetsov SA, Riminucci M, Ziran N, Tsutsui TW, Corsi A. et al. 2004. The interplay of osteogenesis and hematopoiesis: Expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow. J. Cell Biol. 167:1113–22 [Google Scholar]
  111. Larson BL, Ylostalo J, Prockop DJ. 2008. Human multipotent stromal cells undergo sharp transition from division to development in culture. Stem Cells 26:193–201 [Google Scholar]
  112. Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H. et al. 2008. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371:1579–86 [Google Scholar]
  113. Le Blanc K, Mougiakakos D. 2012. Multipotent mesenchymal stromal cells and the innate immune system. Nat. Rev. Immunol. 12:383–96 [Google Scholar]
  114. Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M. et al. 2004. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363:1439–41 [Google Scholar]
  115. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O. 2003a. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp. Hematol. 31:890–96 [Google Scholar]
  116. Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringden O. 2003b. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand. J. Immunol. 57:11–20 [Google Scholar]
  117. Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT. et al. 2004. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 40:1275–84 [Google Scholar]
  118. Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J. et al. 2009. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 5:54–63 [Google Scholar]
  119. Li Y, Lin F. 2012. Mesenchymal stem cells are injured by complement after their contact with serum. Blood 120:3436–43 [Google Scholar]
  120. Liu Y, Wang L, Kikuiri T, Akiyama K, Chen C. et al. 2011. Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. Nat. Med. 17:1594–601 [Google Scholar]
  121. Maes C, Kobayashi T, Selig MK, Torrekens S, Roth SI. et al. 2010. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev. Cell 19:329–44 [Google Scholar]
  122. Mankani MH, Kuznetsov SA, Shannon B, Nalla RK, Ritchie RO. et al. 2006. Canine cranial reconstruction using autologous bone marrow stromal cells. Am. J. Pathol. 168:542–50 [Google Scholar]
  123. Martin PJ, Uberti JP, Soiffer RJ, Klingemann H, Waller EK. et al. 2010. Prochymal improves response rates in patients with steroid-refractory acute graft versus host disease (SR-GVHD) involving the liver and gut: results of a randomized, placebo-controlled, multicenter phase III trial in GVHD. Biol. Blood Marrow Transpl. 16:S169–S70 [Google Scholar]
  124. Martinez C, Hofmann TJ, Marino R, Dominici M, Horwitz EM. 2007. Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs. Blood 109:4245–48 [Google Scholar]
  125. Mason C, Mason J, Culme-Seymour EJ, Bonfiglio GA, Reeve BC. 2013. Cell therapy companies make strong progress from October 2012 to March 2013 amid mixed stock market sentiment. Cell Stem Cell 12:644–47 [Google Scholar]
  126. Mason C, McCall MJ, Culme-Seymour EJ, Suthasan S, Edwards-Parton S. et al. 2012. The global cell therapy industry continues to rise during the second and third quarters of 2012. Cell Stem Cell 11:735–39 [Google Scholar]
  127. Medici D, Shore EM, Lounev VY, Kaplan FS, Kalluri R, Olsen BR. 2010. Conversion of vascular endothelial cells into multipotent stem-like cells. Nat. Med. 16:1400–6 [Google Scholar]
  128. Melero-Martin JM, De Obaldia ME, Kang SY, Khan ZA, Yuan L. et al. 2008. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ. Res. 103:194–202 [Google Scholar]
  129. Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD. et al. 2010. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466:829–34 [Google Scholar]
  130. Mielcarek M, Storb R, Georges GE, Golubev L, Nikitine A. et al. 2011. Mesenchymal stromal cells fail to prevent acute graft-versus-host disease and graft rejection after dog leukocyte antigen-haploidentical bone marrow transplantation. Biol. Blood Marrow Transplant. 17:214–25 [Google Scholar]
  131. Minasi MG, Riminucci M, De Angelis L, Borello U, Berarducci B. et al. 2002. The meso-angioblast: a multipotent, self-renewing cell that originates from the dorsal aorta and differentiates into most mesodermal tissues. Development 129:2773–83 [Google Scholar]
  132. Moioli EK, Clark PA, Chen M, Dennis JE, Erickson HP. et al. 2008. Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. PLOS ONE 3:e3922 [Google Scholar]
  133. Moll G, Jitschin R, von Bahr L, Rasmusson-Duprez I, Sundberg B. et al. 2011. Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses. PLOS ONE 6:e21703 [Google Scholar]
  134. Moll G, Rasmusson-Duprez I, von Bahr L, Connolly-Andersen AM, Elgue G. et al. 2012. Are therapeutic human mesenchymal stromal cells compatible with human blood?. Stem Cells 30:1565–74 [Google Scholar]
  135. Morrison SJ, Scadden DT. 2014. The bone marrow niche for haematopoietic stem cells. Nature 505:327–34 [Google Scholar]
  136. Muraglia A, Cancedda R, Quarto R. 2000. Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J. Cell Sci. 113:Pt. 71161–66 [Google Scholar]
  137. Muraglia A, Corsi A, Riminucci M, Mastrogiacomo M, Cancedda R. et al. 2003. Formation of a chondro-osseous rudiment in micromass cultures of human bone-marrow stromal cells. J. Cell Sci. 116:2949–55 [Google Scholar]
  138. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM. et al. 2002. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29 [Google Scholar]
  139. Nancy P, Tagliani E, Tay CS, Asp P, Levy DE, Erlebacher A. 2012. Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface. Science 336:1317–21 [Google Scholar]
  140. Nasu A, Ikeya M, Yamamoto T, Watanabe A, Jin Y. et al. 2013. Genetically matched human iPS cells reveal that propensity for cartilage and bone differentiation differs with clones, not cell type of origin. PLOS ONE 8:e53771 [Google Scholar]
  141. Nauta AJ, Westerhuis G, Kruisselbrink AB, Lurvink EG, Willemze R, Fibbe WE. 2006. Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. Blood 108:2114–20 [Google Scholar]
  142. Niehans P. 1969. 42 Years of Cellular Therapy. La Tour-de-Peilz: Burier
  143. Okita K, Ichisaka T, Yamanaka S. 2007. Generation of germline-competent induced pluripotent stem cells. Nature 448:313–17 [Google Scholar]
  144. Olsen BR, Reginato AM, Wang W. 2000. Bone development. Annu. Rev. Cell Dev. Biol. 16:191–220 [Google Scholar]
  145. Omatsu Y, Sugiyama T, Kohara H, Kondoh G, Fujii N. et al. 2010. The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity 33:387–99 [Google Scholar]
  146. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC. et al. 1997. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765–71 [Google Scholar]
  147. Owen M, Friedenstein AJ. 1988. Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found. Symp. 136:42–60 [Google Scholar]
  148. Phillips MD, Kuznetsob SA, Cherman N, Park K, Chen KG. et al. 2014. Directed differentiation of human pluripotent induced stem cells toward bone and cartilage: in vitro versus in vivo assays. Stem Cell Transl. Med. 3:867–78 [Google Scholar]
  149. Piersanti S, Remoli C, Saggio I, Funari A, Michienzi S. et al. 2010. Transfer, analysis, and reversion of the fibrous dysplasia cellular phenotype in human skeletal progenitors. J. Bone Miner. Res. 25:1103–16 [Google Scholar]
  150. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R. et al. 1999. Multilineage potential of adult human mesenchymal stem cells. Science 284:143–47 [Google Scholar]
  151. Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A. et al. 2008. IFN-γ activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur. J. Immunol. 38:1745–55 [Google Scholar]
  152. Prockop DJ. 1997. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74 [Google Scholar]
  153. Prockop DJ. 2007. “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clin. Pharmacol. Ther. 82:241–43 [Google Scholar]
  154. Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V. et al. 2001. Repair of large bone defects with the use of autologous bone marrow stromal cells. N. Engl. J. Med. 344:385–86 [Google Scholar]
  155. Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T. et al. 2010. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature 464:852–57 [Google Scholar]
  156. Riminucci M, Collins MT, Corsi A, Boyde A, Murphey MD. et al. 2001. Gnathodiaphyseal dysplasia: a syndrome of fibro-osseous lesions of jawbones, bone fragility, and long bone bowing. J. Bone Miner. Res. 16:1710–18 [Google Scholar]
  157. Riminucci M, Collins MT, Fedarko NS, Cherman N, Corsi A. et al. 2003. FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J. Clin. Investig. 112:683–92 [Google Scholar]
  158. Robey PG, Kuznetsov SA, Riminucci M, Bianco P. 2014. Bone marrow stromal cell assays: in vitro and in vivo. Methods Mol. Biol. 1130:279–93 [Google Scholar]
  159. Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S. et al. 2007. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–36 [Google Scholar]
  160. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. 2010. FOXP3+ regulatory T cells in the human immune system. Nat. Rev. Immunol. 10:490–500 [Google Scholar]
  161. Santagati F, Rijli FM. 2003. Cranial neural crest and the building of the vertebrate head. Nat. Rev. Neurosci. 4:806–18 [Google Scholar]
  162. Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG. et al. 2011. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469:415–18 [Google Scholar]
  163. Schmitt-Gräff A, Skalli O, Gabbiani G. 1989. α-Smooth muscle actin is expressed in a subset of bone marrow stromal cells in normal and pathological conditions. Virchows Arch. B Cell Pathol. 57:291–302 [Google Scholar]
  164. Schroeder T. 2011. Long-term single-cell imaging of mammalian stem cells. Nat. Methods 8:S30–35 [Google Scholar]
  165. Seale P, Bjork B, Yang W, Kajimura S, Chin S. et al. 2008. PRDM16 controls a brown fat/skeletal muscle switch. Nature 454:961–67 [Google Scholar]
  166. Serafini M, Sacchetti B, Pievani A, Redaelli D, Remoli C. et al. 2014. Establishment of bone marrow and hematopoietic niches in vivo by reversion of chondrocyte differentiation of human bone marrow stromal cells. Stem Cell Res. 12:659–72 [Google Scholar]
  167. Sherwood RI, Christensen JL, Conboy IM, Conboy MJ, Rando TA. et al. 2004. Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell 119:543–54 [Google Scholar]
  168. Shi S, Gronthos S. 2003. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J. Bone Miner. Res. 18:696–704 [Google Scholar]
  169. Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ. et al. 2006. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat. Genet. 38:525–27 [Google Scholar]
  170. Simmons PJ, Masinovsky B, Longenecker BM, Berenson R, Torok-Storb B, Gallatin WM. 1992. Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood 80:388–95 [Google Scholar]
  171. Skrahin A, Ahmed RK, Ferrara G, Rane L, Poiret T. et al. 2014. Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial. Lancet Respir. Med. 2:108–22 [Google Scholar]
  172. Song J, Kiel MJ, Wang Z, Wang J, Taichman RS. et al. 2010. An in vivo model to study and manipulate the hematopoietic stem cell niche. Blood 115:2592–600 [Google Scholar]
  173. Spangrude GJ, Heimfeld S, Weissman IL. 1988. Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62 [Google Scholar]
  174. Stappenbeck TS, Miyoshi H. 2009. The role of stromal stem cells in tissue regeneration and wound repair. Science 324:1666–69 [Google Scholar]
  175. Streeter GL. 1949. Developmental horizons in human embryos: review of the histogenesis of cartilage and bone. Contrib. Embryol. 33:149–69 [Google Scholar]
  176. Sudres M, Norol F, Trenado A, Grégoire S, Charlotte F. et al. 2006. Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J. Immunol. 176:7761–67 [Google Scholar]
  177. Sugiyama T, Kohara H, Noda M, Nagasawa T. 2006. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25:977–88 [Google Scholar]
  178. Takada I, Mihara M, Suzawa M, Ohtake F, Kobayashi S. et al. 2007. A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-γ transactivation. Nat. Cell Biol. 9:1273–85 [Google Scholar]
  179. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T. et al. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–72 [Google Scholar]
  180. Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–76 [Google Scholar]
  181. Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M. et al. 2008. White fat progenitor cells reside in the adipose vasculature. Science 322:583–86 [Google Scholar]
  182. Tavassoli M, Crosby WH. 1968. Transplantation of marrow to extramedullary sites. Science 161:54–56 [Google Scholar]
  183. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ. et al. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282:1145–47 [Google Scholar]
  184. Tormin A, Li O, Brune JC, Walsh S, Schutz B. et al. 2011. CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization. Blood 117:5067–77 [Google Scholar]
  185. Uezumi A, Fukada S, Yamamoto N, Takeda S, Tsuchida K. 2010. Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat. Cell Biol. 12:143–52 [Google Scholar]
  186. Urist MR, Nogami H. 1970. Morphogenetic substratum for differentiation of cartilage in tissue culture. Nature 225:1051–52 [Google Scholar]
  187. Urist MR, Strates BS. 1971. Bone morphogenetic protein. J. Dent. Res. 50:1392–406 [Google Scholar]
  188. Viswanathan S, Keating A, Deans R, Hematti P, Prockop D. et al. 2014. Soliciting strategies for developing cell-based reference materials to advance MSC research and clinical translation. Stem Cells Dev. 23:1157–67 [Google Scholar]
  189. von Bahr L, Batsis I, Moll G, Hagg M, Szakos A. et al. 2012. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. Stem Cells 30:1575–78 [Google Scholar]
  190. Voronoff S. 1920. Life: A Study of the Means of Restoring Vital Energy and Prolonging Life New York: EP Dutton & Co.
  191. Wang G, Bunnell BA, Painter RG, Quiniones BC, Tom S. et al. 2005. Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc. Natl. Acad. Sci. USA 102:186–91 [Google Scholar]
  192. Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. 2010. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLOS ONE 5:e10088 [Google Scholar]
  193. Weiss L. 1976. The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anat. Rec. 186:161–84 [Google Scholar]
  194. Weiss L. 1980. The haemopoietic microenvironment of bone marrow: an ultrastructural study of the interactions of blood cells, stroma and blood vessels. Ciba Found. Symp. 71:3–19 [Google Scholar]
  195. Weissman IL. 2002. The road ended up at stem cells. Immunol. Rev. 185:159–74 [Google Scholar]
  196. Westen H, Bainton DF. 1979. Association of alkaline-phosphatase-positive reticulum cells in bone marrow with granulocytic precursors. J. Exp. Med. 150:919–37 [Google Scholar]
  197. Whitfield MJ, Lee WC, Van Vliet KJ. 2013. Onset of heterogeneity in culture-expanded bone marrow stromal cells. Stem Cell Res. 11:1365–77 [Google Scholar]
  198. Willis RA. 1958. The Borderland of Embryology and Pathology London: Butterworth
  199. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. 2000. Adult rat and human bone marrow stromal cells differentiate into neurons. J. Neurosci. Res. 61:364–70 [Google Scholar]
  200. Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ. et al. 1988. Novel regulators of bone formation: molecular clones and activities. Science 242:1528–34 [Google Scholar]
  201. Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL. 2001. Physiological migration of hematopoietic stem and progenitor cells. Science 294:1933–36 [Google Scholar]
  202. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH. et al. 2012. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366–76 [Google Scholar]
  203. Ye L, Fan Z, Yu B, Chang J, Al Hezaimi K. et al. 2012. Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs. Cell Stem Cell 11:50–61 [Google Scholar]
  204. Ylostalo J, Bazhanov N, Prockop DJ. 2008. Reversible commitment to differentiation by human multipotent stromal cells in single-cell-derived colonies. Exp. Hematol. 36:1390–402 [Google Scholar]
  205. Zhang J, Niu C, Ye L, Huang H, He X. et al. 2003. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425:836–41 [Google Scholar]
/content/journals/10.1146/annurev-cellbio-100913-013132
Loading
/content/journals/10.1146/annurev-cellbio-100913-013132
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error