Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyocytes. Isolation and induction of these cells could provide a new therapeutic tool for replacing damaged or lost adult tissues. However, the biological properties and use of stem cells in a clinical setting must be well established before significant clinical benefits are obtained. This paper summarizes data on the biological properties of MSCs and discusses current and potential clinical applications. 1. Introduction A stem cell is an undifferentiated cell with the capacity for multilineage differentiation and self-renewal without senescence. Totipotent stem cells (zygotes) can give rise to a full viable organism and pluripotent stem cells (embryonic stem (ES) cells) can differentiate into any cell type within in the human body. By contrast, trophoblasts are multipotent stem cells that can differentiate into some (e.g., mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs)), but not all, cell types. Adult tissues have specific stem cell niches, which supply replacement cells during normal cell turnover and tissue regeneration following injury [1–3]. The epidermis, hair, HSCs, and the gastrointestinal tract all present good examples of tissues with niches that contribute stem cells during normal cellular turnover [3]. The exact locations of these stem cell niches are poorly understood, but there is growing evidence suggesting a close relationship with pericytes [1, 4, 5] (Figure 1). MSCs have been isolated from adipose tissue [6], tendon [7], periodontal ligament [8], synovial membranes [9], trabecular bone [10], bone marrow [11], embryonic tissues [12], the nervous system [13], skin [14], periosteum [9], and muscle [15]. These adult stem cells were once thought to be committed cell lines that could give rise to only one type of cell, but are now known to have a much greater level of plasticity [16, 17]. Despite the vast variety of source tissues, MSCs show some common characteristics that support the hypothesis of a common origin [1, 18]. These characteristics are: fibroblast like shape in culture, multipotent differentiation, extensive proliferation
References
[1]
L. D. S. Meirelles, P. C. Chagastelles, and N. B. Nardi, “Mesenchymal stem cells reside in virtually all post-natal organs and tissues,” Journal of Cell Science, vol. 119, no. 11, pp. 2204–2213, 2006.
[2]
A. I. Caplan, “Adult mesenchymal stem cells for tissue engineering versus regenerative medicine,” Journal of Cellular Physiology, vol. 213, no. 2, pp. 341–347, 2007.
[3]
E. Fuchs and J. A. Segre, “Stem cells: a new lease on life,” Cell, vol. 100, no. 1, pp. 143–155, 2000.
[4]
M. J. Doherty, B. A. Ashton, S. Walsh, J. N. Beresford, M. E. Grant, and A. E. Canfield, “Vascular pericytes express osteogenic potential in vitro and in vivo,” Journal of Bone and Mineral Research, vol. 13, no. 5, pp. 828–838, 1998.
[5]
P. Bianco, M. Riminucci, S. Gronthos, and P. G. Robey, “Bone marrow stromal stem cells: nature, biology, and potential applications,” Stem Cells, vol. 19, no. 3, pp. 180–192, 2001.
[6]
P. A. Zuk, M. Zhu, H. Mizuno et al., “Multilineage cells from human adipose tissue: implications for cell-based therapies,” Tissue Engineering, vol. 7, no. 2, pp. 211–228, 2001.
[7]
R. Salingcarnboriboon, H. Yoshitake, K. Tsuji et al., “Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property,” Experimental Cell Research, vol. 287, no. 2, pp. 289–300, 2003.
[8]
B. M. Seo, M. Miura, S. Gronthos et al., “Investigation of multipotent postnatal stem cells from human periodontal ligament,” The Lancet, vol. 364, no. 9429, pp. 149–155, 2004.
[9]
C. de Bari, F. Dell'accio, and T. Przemyslaw, “Multipotent mesenchymal stem cells from adult human synovial membrane,” Arthritis & Rheumatism, vol. 44, no. 8, pp. 1928–1942, 2001.
[10]
R. Tuli, S. Tuli, S. Nandi et al., “Characterization of Multipotential Mesenchymal Progenitor Cells Derived from Human Trabecular Bone,” Stem Cells, vol. 21, no. 6, pp. 681–693, 2003.
[11]
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.
[12]
J. A. Thomson, “Embryonic stem cell lines derived from human blastocysts,” Science, vol. 282, no. 5391, pp. 1145–1147, 1998.
[13]
R. Poulsom, M. R. Alison, S. J. Forbes, and N. A. Wright, “Muscle stem cells,” Journal of Pathology, vol. 197, no. 4, pp. 457–467, 2002.
[14]
J. G. Toma, M. Akhavan, K. J. L. Fernandes et al., “Isolation of multipotent adult stem cells from the dermis of mammalian skin,” Nature Cell Biology, vol. 3, no. 9, pp. 778–784, 2001.
[15]
A. Asakura, M. Komaki, and M. A. Rudnicki, “Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation,” Differentiation, vol. 68, no. 4-5, pp. 245–253, 2001.
[16]
H. J. Rippon and A. E. Bishop, “Embryonic stem cells,” Cell Proliferation, vol. 37, no. 1, pp. 23–34, 2004.
[17]
H. E. Young, T. A. Steele, R. A. Bray et al., “Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors,” Anatomical Record, vol. 264, no. 1, pp. 51–62, 2001.
[18]
S. Kern, H. Eichler, J. Stoeve, H. Klüter, and K. Bieback, “Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue,” Stem Cells, vol. 24, no. 5, pp. 1294–1301, 2006.
[19]
P. A. Zuk, M. Zhu, H. Mizuno et al., “Multilineage cells from human adipose tissue: implications for cell-based therapies,” Tissue Engineering, vol. 7, no. 2, pp. 211–228, 2001.
[20]
P. A. Zuk, “The adipose-derived stem cell: looking back and looking ahead,” Molecular Biology of the Cell, vol. 21, no. 11, pp. 1783–1787, 2010.
[21]
B. M. Strem, K. C. Hicok, M. Zhu et al., “Multipotential differentiation of adipose tissue-derived stem cells,” Keio Journal of Medicine, vol. 54, no. 3, pp. 132–141, 2005.
[22]
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.
[23]
P. H. Krebsbach, S. A. Kuznetsov, P. Bianco, and P. Gehron Robey, “Bone marrow stromal cells: characterization and clinical application,” Critical Reviews in Oral Biology and Medicine, vol. 10, no. 2, pp. 165–181, 1999.
[24]
A. J. Friedenstein, R. K. Chailakhjan, and K. S. Lalykina, “The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells,” Cell and Tissue Kinetics, vol. 3, no. 4, pp. 393–403, 1970.
[25]
H. Castro-Malaspina, R. E. Gay, and G. Resnick, “Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny,” Blood, vol. 56, no. 2, pp. 289–301, 1980.
[26]
R. G. Fei, P. E. Penn, and N. S. Wolf, “A method to establish pure fibroblast and endothelial cell colony cultures from murine bone marrow,” Experimental Hematology, vol. 18, no. 8, pp. 953–957, 1990.
[27]
J. J. Song, A. J. Celeste, F. M. Kong, R. L. Jirtle, V. Rosen, and R. S. Thies, “Bone morphogenetic protein-9 binds to liver cells and stimulates proliferation,” Endocrinology, vol. 136, no. 10, pp. 4293–4297, 1995.
[28]
R. K. Chailakhyan and K. S. Lalykina, “Spontaneous and induced differentiation of osseous tissue in a population of fibroblast-like cells obtained from long-term monolayer cultures of bone marrow and spleen,” Doklady Akademii nauk SSSR, vol. 187, no. 2, pp. 473–475, 1969.
[29]
B. A. Ashton, T. D. Allen, C. R. Howlett, C. C. Eaglesom, A. Hattori, and M. Owen, “Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo,” Clinical Orthopaedics and Related Research, no. 151, pp. 294–307, 1980.
[30]
H. M. Patt, M. A. Maloney, and M. L. Flannery, “Hematopoietic microenvironment transfer by stromal fibroblasts derived from bone marrow varying in cellularity,” Experimental Hematology, vol. 10, no. 9, pp. 738–742, 1982.
[31]
M. Owen, “Marrow stromal stem cells,” Journal of Cell Science, vol. 105, no. 12, pp. 1663–1668, 1988.
[32]
J. H. Bennett, C. J. Joyner, J. T. Triffitt, and M. E. Owen, “Adipocytic cells cultured from marrow have osteogenic potential,” Journal of Cell Science, vol. 99, no. 1, pp. 131–139, 1991.
[33]
A. I. Caplan, “Mesenchymal stem cells,” Journal of Orthopaedic Research, vol. 9, no. 5, pp. 641–650, 1991.
[34]
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.
[35]
M. K. Majumdar, M. A. Thiede, J. D. Mosca, et al., “Phenotypic and functional comparison of cultures of marrow –derived mesenchymal stem cells (MSCs) and stromal cells,” Journal of Cellular Physiology, vol. 176, no. 1, pp. 57–66, 1998.
[36]
S. E. Haynesworth, M. A. Baber, and A. I. Caplan, “Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies,” Bone, vol. 13, no. 1, pp. 69–80, 1992.
[37]
H. Yoshimura, T. Muneta, A. Nimura, A. Yokoyama, H. Koga, and I. Sekiya, “Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle,” Cell and Tissue Research, vol. 327, no. 3, pp. 449–462, 2007.
[38]
S. Gronthos, A. C. W. Zannettino, S. J. Hay et al., “Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow,” Journal of Cell Science, vol. 116, no. 9, pp. 1827–1835, 2003.
[39]
F. L. Ulmer, A. Winkel, P. Kohorst, and M. Stiesch, “Stem cells—prospects in dentistry,” Schweizer Monatsschrift für Zahnmedizin, vol. 120, no. 10, pp. 860–883, 2010.
[40]
B. B. Benatti, K. G. Silverio, M. Z. Casati, et al., “Physiological features of periodontal regeneration and approaches for periodontal tissue engineering utilizing periodontal ligament cells,” Journal of Bioscience and Bioengineering, vol. 103, no. 1, pp. 1–6, 2007.
[41]
G. T. J. Huang, S. Gronthos, and S. Shi, “Critical reviews in oral biology & medicine: mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in Regenerative Medicine,” Journal of Dental Research, vol. 88, no. 9, pp. 792–806, 2009.
[42]
I. C. Gay, S. Chen, and M. MacDougall, “Isolation and characterization of multipotent human periodontal ligament stem cells,” Orthodontics & craniofacial research, vol. 10, no. 3, pp. 149–160, 2007.
[43]
B. Lindroos, K. Maenpaa, T. Ylikomi, et al., “Characterisation of human dental stem cells and buccal mucosa fibroblasts,” Biochemical and Biophysical Research Communications, vol. 368, no. 2, pp. 329–335, 2008.
[44]
J. Xu, W. Wang, Y. Kapila, J. Lotz, and S. Kapila, “Multiple differentiation capacity of STRO-1+/CD146+ PDL Mesenchymal Progenitor Cells,” Stem Cells and Development, vol. 18, no. 3, pp. 487–496, 2009.
[45]
J. N. Beresford, J. A. Gallagher, J. W. Poser, and R. G. G. Russell, “Production of osteocalcin by human bone cells in vitro. Effects of 1,25(OH)2D3, 24,25(OH)2D3, parathyroid hormone, and glucocorticoids,” Metabolic Bone Disease and Related Research, vol. 5, no. 5, pp. 229–234, 1984.
[46]
B. R. MacDonald, J. A. Gallagher, and I. Ahnfelt-Ronne, “Effects of bovine parathyroid hormone and 1,25-dihydroxyvitamin D3 on the production of prostaglandins by cells derived from human bone,” FEBS Letters, vol. 169, no. 1, pp. 49–52, 1984.
[47]
J. E. Wergedal and D. J. Baylink, “Characterization of cells isolated and cultured from human bone,” Proceedings of the Society for Experimental Biology and Medicine, vol. 176, no. 1, pp. 60–69, 1984.
[48]
P. G. Robey and J. D. Termine, “Human bone cells in vitro,” Calcified Tissue International, vol. 37, no. 5, pp. 453–460, 1985.
[49]
V. Sottile, C. Halleux, F. Bassilana, H. Keller, and K. Seuwen, “Stem cell characteristics of human trabecular bone-derived cells,” Bone, vol. 30, no. 5, pp. 699–704, 2002.
[50]
F. Vandenabeele, C. de Bari, M. Moreels, et al., “Morphological and immunocytochemical characterization of cultured fibroblast-like cells derived from adult human synovial membrane,” Archives of Histology and Cytology, vol. 66, no. 2, pp. 45–53, 2003.
[51]
F. Djouad, C. Bony, T. H？upl et al., “Transcriptional profiles discriminate bone marrow-derived and synovium-derived mesenchymal stem cells,” Arthritis Research & Therapy, vol. 7, no. 6, pp. R1304–1315, 2005.
[52]
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.
[53]
X. Zhang, A. Naik, C. Xie et al., “Periosteal stem cells are essential for bone revitalization and repair,” Journal of Musculoskeletal Neuronal Interactions, vol. 5, no. 4, pp. 360–362, 2005.
[54]
C. Perka, O. Schultz, R. S. Spitzer, K. Lindenhayn, G. R. Burmester, and M. Sittinger, “Segmental bone repair by tissue-engineered periosteal cell transplants with bioresorbable fleece and fibrin scaffolds in rabbits,” Biomaterials, vol. 21, no. 11, pp. 1145–1153, 2000.
[55]
B. Johnstone, T. M. Hering, A. I. Caplan, V. M. Goldberg, and J. U. Yoo, “In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells,” Experimental Cell Research, vol. 238, no. 1, pp. 265–272, 1998.
[56]
P. Seale, A. Asakura, and M. A. Rudnicki, “The Potential of Muscle Stem Cells,” Developmental Cell, vol. 1, no. 3, pp. 333–342, 2001.
[57]
Z. Qu-Petersen, B. Deasy, R. Jankowski et al., “Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration,” Journal of Cell Biology, vol. 157, no. 5, pp. 851–864, 2002.
[58]
F. Relaix and C. Marcelle, “Muscle stem cells,” Current Opinion in Cell Biology, vol. 21, no. 6, pp. 748–753, 2009.
[59]
K. A. Jackson, T. Mi, and M. A. Goodell, “Hematopoietic potential of stem cells isolated from murine skeletal muscle,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 25, pp. 14482–14486, 1999.
[60]
E. Gussoni, Y. Soneoka, C. D. Strickland et al., “Dystrophin expression in the mdx mouse restored by stem cell transplantation,” Nature, vol. 401, no. 6751, pp. 390–394, 1999.
[61]
S. L. McKinney-Freeman, K. A. Jackson, F. D. Camargo, G. Ferrari, F. Mavilio, and M. A. Goodell, “Muscle-derived hematopoietic stem cells are hematopoietic in origin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 3, pp. 1341–1346, 2002.
[62]
R. Vishnubalaji, M. Manikandan, M. Al-Nbaheen, et al., “In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells,” BMC Developmental Biology, vol. 12, p. 7, 2012.
[63]
C. M. Shi and T. M. Cheng, “Differentiation of dermis-derived multipotent cells into insulin-producing pancreatic cells in vitro,” World Journal of Gastroenterology, vol. 10, no. 17, pp. 2550–2552, 2004.
[64]
D. T. B. Shih, D. C. Lee, S. C. Chen et al., “Isolation and characterization of neurogenic mesenchymal stem cells in human scalp tissue,” Stem Cells, vol. 23, no. 7, pp. 1012–1020, 2005.
[65]
M. A. Haniffa, X. N. Wang, U. Holtick et al., “Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells,” Journal of Immunology, vol. 179, no. 3, pp. 1595–1604, 2007.
[66]
F. G. Chen, W. J. Zhang, D. Bi et al., “Clonal analysis of nestin- vimentin+ multipotent fibroblasts isolated from human dermis,” Journal of Cell Science, vol. 120, no. 16, pp. 2875–2883, 2007.
[67]
K. Lorenz, M. Sicker, E. Schmelzer et al., “Multilineage differentiation potential of human dermal skin-derived fibroblasts,” Experimental Dermatology, vol. 17, no. 11, pp. 925–932, 2008.
[68]
H. S. Wang, S. C. Hung, S. T. Peng et al., “Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord,” Stem Cells, vol. 22, no. 7, pp. 1330–1337, 2004.
[69]
U. Nekanti, V. B. Rao, A. G. Bahirvani, M. Jan, S. Totey, and M. Ta, “Long-term expansion and pluripotent marker array analysis of Wharton's jelly-derived mesenchymal stem cells,” Stem Cells and Development, vol. 19, no. 1, pp. 117–130, 2010.
[70]
M. Y. Chen, P. C. Lie, Z. L. Li, and X. Wei, “Endothelial differentiation of Wharton's jelly-derived mesenchymal stem cells in comparison with bone marrow-derived mesenchymal stem cells,” Experimental Hematology, vol. 37, no. 5, pp. 629–640, 2009.
[71]
L. F. Wu, N. N. Wang, Y. S. Liu, and X. Wei, “Differentiation of wharton's jelly primitive stromal cells into insulin-producing cells in comparison with bone marrow mesenchymal stem cells,” Tissue Engineering, vol. 15, no. 10, pp. 2865–2873, 2009.
[72]
Y. N. Zhang, P. C. Lie, and X. Wei, “Differentiation of mesenchymal stromal cells derived from umbilical cord Wharton's jelly into hepatocyte-like cells,” Cytotherapy, vol. 11, no. 5, pp. 548–558, 2009.
[73]
X. Zhang, A. Naik, C. Xie et al., “Periosteal stem cells are essential for bone revitalization and repair,” Journal of Musculoskeletal Neuronal Interactions, vol. 5, no. 4, pp. 360–362, 2005.
[74]
T. Barberi, P. Klivenyi, N. Y. Calingasan et al., “Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice,” Nature Biotechnology, vol. 21, no. 10, pp. 1200–1207, 2003.
[75]
F. Benninger, H. Beck, M. Wernig, K. L. Tucker, O. Brüstle, and B. Scheffler, “Functional integration of embryonic stem cell-derived neurons in hippocampal slice cultures,” Journal of Neuroscience, vol. 23, no. 18, pp. 7075–7083, 2003.
[76]
S. Chiba, Y. Iwasaki, H. Sekino, and N. Suzuki, “Transplantation of motoneuron-enriched neural cells derived from mouse embryonic stem cells improves motor function of hemiplegic mice,” Cell Transplantation, vol. 12, no. 5, pp. 457–468, 2003.
[77]
P. Bianco and P. G. Robey, “Stem cells in tissue engineering,” Nature, vol. 414, no. 6859, pp. 118–121, 2001.
[78]
A. I. Caplan, “Adult mesenchymal stem cells for tissue engineering versus regenerative medicine,” Journal of Cellular Physiology, vol. 213, no. 2, pp. 341–347, 2007.
[79]
Z. Ruszczak and R. A. Schwartz, “Modern aspects of wound healing: an update,” Dermatologic Surgery, vol. 26, no. 3, pp. 219–229, 2000.
[80]
G. Pellegrini, C. E. Traverso, A. T. Franzi, M. Zingirian, R. Cancedda, and M. De Luca, “Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium,” The Lancet, vol. 349, no. 9057, pp. 990–993, 1997.
[81]
S. P. Bruder, K. H. Kraus, V. M. Goldberg, and S. Kadiyala, “The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects,” Journal of Bone and Joint Surgery, vol. 80, no. 7, pp. 985–996, 1998.
[82]
A. A. Kocher, M. D. Schuster, M. J. Szabolcs et al., “Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function,” Nature Medicine, vol. 7, no. 4, pp. 430–436, 2001.
[83]
B. Johnstone and J. U. Yoo, “Autologous mesenchymal progenitor cells in articular cartilage repair,” Clinical Orthopaedics and Related Research, no. 367, pp. S156–S162, 1999.
[84]
S. Gronthos, M. Mankani, J. Brahim, P. G. Robey, and S. Shi, “Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 25, pp. 13625–13630, 2000.
[85]
S. Makino, K. Fukuda, S. Miyoshi et al., “Cardiomyocytes can be generated from marrow stromal cells in vitro,” Journal of Clinical Investigation, vol. 103, no. 5, pp. 697–705, 1999.
[86]
E. Lagasse, H. Connors, M. Al-Dhalimy et al., “Purified hematopoietic stem cells can differentiate into hepatocytes in vivo,” Nature Medicine, vol. 6, no. 11, pp. 1229–1234, 2000.
[87]
V. K. Ramiya, M. Maraist, K. E. Arfors, D. A. Schatz, A. B. Peck, and J. G. Cornelius, “Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells,” Nature Medicine, vol. 6, no. 3, pp. 278–282, 2000.
[88]
A. Bj？rklund, “Cell replacement strategies for neurodegenerative disorders,” Novartis Foundation Symposium, vol. 231, pp. 7–15, 2000.
[89]
G. Ferrari, G. Cusella-De Angelis, M. Coletta et al., “Muscle regeneration by bone marrow-derived myogenic progenitors,” Science, vol. 279, no. 5356, pp. 1528–1530, 1998.
[90]
Y. P. Kato, M. G. Dunn, J. P. Zawadsky, A. J. Tria, and F. H. Silver, “Regeneration of Achilles tendon with a collagen tendon prosthesis: results of a one-year implantation study,” Journal of Bone and Joint Surgery, vol. 73, no. 4, pp. 561–574, 1991.
[91]
R. G. Young, D. L. Butler, W. Weber, A. I. Caplan, S. L. Gordon, and D. J. Fink, “Use of mesenchymal stem cells in a collagen matrix for achilles tendon repair,” Journal of Orthopaedic Research, vol. 16, no. 4, pp. 406–413, 1998.
[92]
J. Ringe, C. Kaps, G. R. Burmester, and M. Sittinger, “Stem cells for regenerative medicine: advances in the engineering of tissues and organs,” Naturwissenschaften, vol. 89, no. 8, pp. 338–351, 2002.
[93]
H. F. Tse, Y. L. Kwong, J. K. F. Chan, G. Lo, C. L. Ho, and C. P. Lau, “Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation,” The Lancet, vol. 361, no. 9351, pp. 47–49, 2003.
[94]
S. Miyagawa, A. Saito, T. Sakaguchi et al., “Impaired myocardium regeneration with skeletal cell sheets-A preclinical trial for tissue-engineered regeneration therapy,” Transplantation, vol. 90, no. 4, pp. 364–372, 2010.
[95]
S. Wakitani, T. Goto, S. J. Pineda et al., “Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage,” Journal of Bone and Joint Surgery, vol. 76, no. 4, pp. 579–592, 1994.
[96]
H. Klingemann, D. Matzilevich, and J. Marchand, “Mesenchymal stem cells-sources and clinical applications,” Transfusion Medicine and Hemotherapy, vol. 35, no. 4, pp. 272–277, 2008.
[97]
K. le Blanc, F. Frassoni, L. Ball, et al., “Developmental committee of the European group for blood and marrow transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study,” The Lancet, vol. 371, no. 9624, pp. 1579–1586, 2008.
[98]
M. Duijvestein, A. C. W. Vos, H. Roelofs et al., “Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study,” Gut, vol. 59, no. 12, pp. 1662–1669, 2010.
[99]
A. Tyndall, “Application of autologous stem cell transplantation in various adult and pediatric rheumatic diseases,” Pediatric Research, vol. 71, no. 2–4, pp. 433–438, 2012.
[100]
D. Y. Oh, P. Cui, H. Hosseini, et al., “Potently immunosuppressive 5-Fluorouracil-resistant mesenchymal stromal cells completely remit an experimental autoimmune disease,” The Journal of Immunology, vol. 188, no. 5, pp. 2207–2217, 2012.
[101]
S. Morando, T. Vigo, M. Esposito, et al., “The therapeutic effect of mesenchymal stem cell transplantation in experimental autoimmune encephalomyelitis is mediated by peripheral and central mechanisms,” Stem Cell Research & Therapy, vol. 3, no. 1, p. 3, 2012.
[102]
P. J. Darlington, M. N. Boivin, and A. Bar-Or, “Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis,” Expert Review of Neurotherapeutics, vol. 11, no. 9, pp. 1295–1303, 2011.
[103]
E. W. Choi, I. S. Shin, S. Y. Park, et al., “Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation,” Arthritis & Rheumatism, vol. 64, no. 1, pp. 243–253, 2012.
[104]
A. Tyndall, “Successes and failures of stem cell transplantation in autoimmune diseases,” American Society of Hematology Education Program, vol. 2011, pp. 280–284, 2011.
[105]
E. J. Bassi, D. C. de Almeida, P. M. Moraes-Vieira, and N. O. Camara, “Exploring the role of soluble factors associated with immune regulatory properties of mesenchymal stem cells,” Stem Cell Reviews. In press.
[106]
G. Martino, R. J. M. Franklin, A. B. Van Evercooren, and D. A. Kerr, “Stem cell transplantation in multiple sclerosis: current status and future prospects,” Nature Reviews Neurology, vol. 6, no. 5, pp. 247–255, 2010.
[107]
M. S. Freedman, A. Bar-Or, H. L. Atkins et al., “The therapeutic potential of mesenchymal stem cell transplantation as a treatment for multiple sclerosis: consensus report of the international MSCT study group,” Multiple Sclerosis, vol. 16, no. 4, pp. 503–510, 2010.
[108]
M. R.-V. Rhijn, W. Weimar, and M. J. Hoogduijn, “Mesenchymal stem cells: application for solid-organ transplantation,” Current Opinion in Organ Transplantation, vol. 17, no. 1, pp. 55–62, 2012.
[109]
L. Lu, R. N. Shen, and H. E. Broxmeyer, “Stem cells from bone marrow, umbilical cord and peripheral blood fro clinical application: current status and future application,” Critical Reviews in Oncology / Hematology, vol. 22, no. 2, pp. 61–78, 1996.
[110]
G. Ferrari, G. Cusella-De Angelis, M. Coletta et al., “Muscle regeneration by bone marrow-derived myogenic progenitors,” Science, vol. 279, no. 5356, pp. 1528–1530, 1998.
[111]
J. Sanchez-Ramos, S. Song, F. Cardozo-Pelaez et al., “Adult bone marrow stromal cells differentiate into neural cells in vitro,” Experimental Neurology, vol. 164, no. 2, pp. 247–256, 2000.
[112]
N. Terada, T. Hamazaki, M. Oka et al., “Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion,” Nature, vol. 416, no. 6880, pp. 542–545, 2002.
[113]
A. Trounson, R. G. Thakar, G. Lomax, and D. Gibbons, “Clinical trials for stem cell therapies,” BMC Medicine, vol. 9, p. 52, 2011.
[114]
B. Lindroos, S. Boucher, L. Chase et al., “Serum-free, xeno-free culture media maintain the proliferation rate and multipotentiality of adipose stem cells in vitro,” Cytotherapy, vol. 11, no. 7, pp. 958–972, 2009.
[115]
B. Lindroos, K. L. Aho, H. Kuokkanen et al., “Differential gene expression in adipose stem cells cultured in allogeneic human serum versus fetal bovine serum,” Tissue Engineering, vol. 16, no. 7, pp. 2281–2294, 2010.
