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Archives of Pharmacal Research

, Volume 35, Issue 2, pp 201–211 | Cite as

Perspectives on mesenchymal stem cells: Tissue repair, immune modulation, and tumor homing

  • Hyun Sook Hong
  • Yeong Hoon Kim
  • Youngsook SonEmail author
Review

Abstract

Mesenchymal stem cells (MSCs) or MSC-like cells have been identified in a variety of different tissues that share molecular expression profiles and biological functions but also retain a unique differentiation preference depending on their tissue origins. MSCs play beneficial roles in the healing of damaged tissue by directly differentiating to many different resident cell types and/or by secreting several trophic factors that aid tissue repair. Aside from MSCs’ reparative stem cell function, they drive immune responses toward immunosuppression and anti-inflammation. This novel function of MSCs opens up new avenues for clinical development of MSC immune-therapeutics to treat uncontrollable, life threatening, severe, chronic inflammation and autoimmune disease. Unexpectedly high rates of MSCs’ tumor homing capacity and their tumor supporting capability have also been noted in tumor-bearing animal models. In this review, we will discuss MSCs’ basic cell biology and perspectives on MSCs in terms of tissue repair, immune modulation, and tumor homing.

Key words

MSC Tissue repair Immune modulation Tumor homing Adipose stem cell Inflammation 

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References

  1. Abdi, R., Fiorina, P., Adra, C. N., Atkinson, M., and Sayegh, M. H., Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes, 57, 1759–1767 (2008).PubMedCrossRefGoogle Scholar
  2. Aggarwal, S. and Pittenger, M. F., Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 105, 1815–1822 (2005).PubMedCrossRefGoogle Scholar
  3. Ahmed, F., Steele, J. C., Herbert, J. M., Steven, N. M., and Bicknell, R., Tumor stroma as a target in cancer. Curr. Cancer Drug Targets, 8, 447–453 (2008)PubMedCrossRefGoogle Scholar
  4. Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., and Kuchroo, V. K., Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature, 441, 235–238 (2006).PubMedCrossRefGoogle Scholar
  5. Biron, C. A., Activation and function of natural killer cell responses during viral infections. Curr. Opin. Immunol., 9, 24–34 (1997).PubMedCrossRefGoogle Scholar
  6. Caddick, J., Kindham, P. J., Gardiner, N. J., Wiberg, M., and Terenghi, G., Phenotypic and functional characteristics of mesenchymal sem cells differentiated along a Schwann cell lineage. Glia, 54, 840–849 (2006).PubMedCrossRefGoogle Scholar
  7. Casiraghi, F., Azzollini, N., Cassis, P., Imberti, B., Morigi, M., Cugini, D., Cavinato, R. A., Todeschini, M., Solini, S., Sonzogni, A., Perico, N., Remuzzi, G., and Noris, M., Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells. J. Immunol., 18, 3933–3946 (2008).Google Scholar
  8. Chen, G., Marrow stromal cells for cell-based therapy: the role of antiinflammatory cytokines in cellular cardiomyoplasty. Ann. Thorac. Surg., 90, 190–197 (2010).PubMedCrossRefGoogle Scholar
  9. Chen, L., Tredget, E. E., Wu, P. Y., and Wu, Y., Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS ONE, 3, e1886 (2008).Google Scholar
  10. Chi, G. F., Kim, M. R., Kim, D. W., Jiang, M. H., and Son, Y., Schwann cells differentiated from spheroid-forming cells of rat subcutaneous fat tissue myelinate axons in the spinal cord injury. Exp. Neurol., 222, 304–317 (2010).PubMedCrossRefGoogle Scholar
  11. Ciccocioppo, R., Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn’s disease. Gut, 60, 788–798 (2011).PubMedCrossRefGoogle Scholar
  12. Crigler, L., Robey, R. C., Asawachaicharn, A., Gaupp, D., and Phinney, D. G., Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp. Neurol., 198, 54–64 (2006).PubMedCrossRefGoogle Scholar
  13. Crisan, M., Yap, S., Casteilla, L., Chen, C. W., Corselli, M., Park, T. S., Andriolo, G., Sun, B., Zheng, B., Zhang, L., Norotte, C., Teng, P. N., Traas, J., Schugar, R., Deasy, B. M., Badylak, S., Buhring, H. J., Giacobino, J. P., Lazzari, L., Huard, J., and Péault, B., A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell, 3, 301–313 (2008).PubMedCrossRefGoogle Scholar
  14. D’Agostino, B., Sullo, N., Siniscalco, D., De Angelis, A., and Rossi, F., Mesenchymal stem cell therapy for the treatment of chronic obstructive pulmonary disease. Expert Opin. Biol. Ther., 10, 681–687 (2010).PubMedCrossRefGoogle Scholar
  15. Daley, J. M., Brancato, S. K., Thomay, A. A., Reichner, J. S., and Albina, J. E., The phenotype of murine wound macrophages. J. Leukoc. Biol., 87, 59–67 (2010).PubMedCrossRefGoogle Scholar
  16. Dezawa, M., Takahashi, I., Esaki, M., Takano, M., and Sawada, H., Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. Eur. J. Neurosci., 14, 1771–1776 (2001).PubMedCrossRefGoogle Scholar
  17. Di Nicola, M., Carlo-Stella, C., Magni, M., Milanesi, M., Longoni, P. D., Matteucci, P., Grisanti, S., and Gianni, A. M., Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 99, 3838–3843 (2002).PubMedCrossRefGoogle Scholar
  18. Djouad, F., Plence, P., Bony, C., Tropel, P., Apparailly, F., Sany, J., Noël, D., and Jorgensen, C., Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood, 102, 3837–3844 (2003).PubMedCrossRefGoogle Scholar
  19. Doetsch, F., Caillé, I., Lim, D. A., García-Verdugo, J. M., and Alvarez-Buylla, A., Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell, 97, 703–716 (1999).PubMedCrossRefGoogle Scholar
  20. Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, Dj., and Horwitz, E., Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315–317 (2006).PubMedCrossRefGoogle Scholar
  21. Dwyer, R. M., Mesenchymal stem cells and cancer: tumorspecific delivery vehicles or therapeutic targets? Hum. Gene Ther., 21, 1506–1512 (2010).PubMedCrossRefGoogle Scholar
  22. Friedenstein, A. J., Chailakhjan, R. K., and Lalykina, K. S., The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet., 3, 393–403 (1970).PubMedGoogle Scholar
  23. Gordon, D., Pavlovska, G., Glover, C. P., Uney, J. B., Wraith, D., and Scolding, N. J., Human mesenchymal stem cells abrogate experimental allergic encephalomyelitis after intraperitoneal injection, and with sparse CNS infiltration. Neurosci. Lett., 448, 71–73 (2008).PubMedCrossRefGoogle Scholar
  24. Grisendi, G., Understanding tumor-stroma interplays for targeted therapies by armed mesenchymal stromal progenitors: the Mesenkillers. Am. J. Cancer Res., 1, 787–805 (2011).PubMedGoogle Scholar
  25. Gronthos, S., Franklin, D. M., Leddy, H. A., Robey, P. G., Storms, R. W., and Gimble, J. M., Surface protein characterization of human adipose tissue-derived stromal cells. J. Cell Physiol., 189, 54–63 (2001).PubMedCrossRefGoogle Scholar
  26. Gronthos, S., Arthur, A., Bartold, P. M., and Shi, S., A method to isolate and culture expand human dental pulp stem cells. Methods Mol. Biol., 698, 107–121 (2011).PubMedCrossRefGoogle Scholar
  27. Harris, J. R., Brown, G. A., Jorgensen, M., Kaushal, S., Ellis, E. A., Grant, M. B., and Scott, E. W., Bone marrow-derived cells home to and regenerate retinal pigment epithelium after injury. Invest. Ophthalmol. Vis. Sci., 47, 2108–2113 (2006).PubMedCrossRefGoogle Scholar
  28. Harris, J. R., Fisher, R., Jorgensen, M., Kaushal, S., and Scott, E. W., CD133 progenitor cells from the bone marrow contribute to retinal pigment epithelium repair. Stem Cells, 27, 457–466 (2009).PubMedCrossRefGoogle Scholar
  29. Hattori, K., Dias, S., Heissig, B., Hackett, N. R., Lyden, D., Tateno, M., Hicklin, D. J., Zhu, Z., Witte, L., Crystal, R. G., Moore, M. A., and Rafii, S., Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J. Exp. Med., 193, 1005–1014 (2001).PubMedCrossRefGoogle Scholar
  30. Hong, H. S., Lee, J., Lee, E., Kwon, Y. S., Lee, E., Ahn, W., Jiang, M. H., Kim, J. C., and Son, Y., A new role of substance P as an injury-inducible messenger for mobilization of CD29+ stromal-like cells. Nat. Med., 15, 425–435 (2009).PubMedCrossRefGoogle Scholar
  31. Hong, H.-S., Kim, D. Y., Yoon, K. J., and Son, Y., A new paradigm for stem cell therapy: substance-P as a stem cell-stimulating agent. Arch. Pharm. Res., 34, 2003–2006 (2011).PubMedCrossRefGoogle Scholar
  32. Ip, J. E., Wu, Y., Huang, J., Zhang, L., Pratt, R. E., and Dzau, V. J., Mesenchymal stem cells use integrin beta 1 not CXC chemokine receptor 4 for myocardial migration and engraftment. Mol. Biol. Cell, 18, 2873–2882 (2007).PubMedCrossRefGoogle Scholar
  33. Jiang, L., Zhu, J. K., Liu, X. L., Xiang, P., Hu, J., and Yu, W. H., Differentiation of rat adipose tissue-derived stem cells in to Schwann-like cells in vitro. Neuroreport, 19, 1015–1019 (2008).PubMedCrossRefGoogle Scholar
  34. Jiang, X. X., Zhang, Y., Liu, B., Zhang, S. X., Wu, Y., Yu, X. D., and Mao, N., Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood, 15, 4120–4126 (2005).CrossRefGoogle Scholar
  35. Kassis, I., Grigoriadis, N., Gowda-Kurkalli, B., Mizrachi-Kol, R., Ben-Hur, T., Slavin, S., Abramsky, O., and Karussis, D., Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. Arch. Neurol., 65, 753–761 (2008).PubMedCrossRefGoogle Scholar
  36. Keilhoff, G., Goihl, A., Langnäse, K., Fansa, H., and Wolf, G., Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelination cells. Eur. J. Cell Biol., 85, 11–24 (2006).PubMedCrossRefGoogle Scholar
  37. Kim, J. and Hematti, P., Mesenchymal stem cell-educated macrophages: A novel type of alternatively activated macrophages. Exp. Hematol., 37, 1445–1453 (2009).PubMedCrossRefGoogle Scholar
  38. Kingham, P. J., Kalbermatten, D. F., Mahay, D., Armstrong, S. J., Wiberg, M., and Terenghi, G., Adipose-derived stem cells differentiated into a Schwann cell phenotype and promote neurite outgrowth in vitro. Exp. Neurol., 207, 267–274 (2007).PubMedCrossRefGoogle Scholar
  39. Kocher, A. A., Schuster, M. D., Szabolcs, M. J., Takuma, S., Burkhoff, D., Wang, J., Homma, S., Edwards, N. M., and Itescu, S., Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat. Med., 7, 430–436 (2001).PubMedCrossRefGoogle Scholar
  40. Kokai, L. E., Rubin, J. P., and Marra, K. G., The potential of adipose-derived adult stem cells as a source of neuronal progenitor cells. Plast. Reconstr. Surg., 116, 1453–1460 (2005).PubMedCrossRefGoogle Scholar
  41. Krampera, M., Glennie, S., Dyson, J., Scott, D., Laylor, R., Simpson, E., and Dazzi, F., Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood, 101, 3722–3729 (2003).PubMedCrossRefGoogle Scholar
  42. Kuhn, H. G., Dickinson-Anson, H., and Gage, F. H., Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J. Neurosci., 16, 2027–2033 (1996).PubMedGoogle Scholar
  43. Lange, C., Brunswig-Spickenheier, B., Cappallo-Obermann, H., Eggert, K., Gehling, U. M., Rudolph, C., Schlegelberger, B., Cornils, K., Zustin, J., Spiess, A. N., and Zander, A. R., Radiation rescue: mesenchymal stromal cells protect from lethal irradiation. PLoS ONE, 5, e14486 (2011).Google Scholar
  44. Le Blanc, K., Rasmusson, I., Sundberg, B., Götherström, C., Hassan, M., Uzunel, M., and Ringdén, O., Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet, 363, 1439–1441 (2004).PubMedCrossRefGoogle Scholar
  45. Lewis, E. F., Moye, L. A., Rouleau, J. L., Sacks, F. M., Arnold, J. M., Warnica, J. W., Flaker, G. C., Braunwald, E., and Pfeffer, M. A., Predictors of late development of heart failure in stable survivors of myocardial infarction: the CARE study. J. Am. Coll. Cardiol., 42, 1446–1453 (2003).PubMedCrossRefGoogle Scholar
  46. Li, H., Fan, X., and Houghton, J., Tumor microenvironment: the role of the tumor stroma in cancer. J. Cell. Biochem., 101, 805–815 (2007).PubMedCrossRefGoogle Scholar
  47. Liu, X. J., Zhang, J. F., Sun, B., Peng, H. S., Kong, Q. F., Bai, S. S., Liu, Y. M., Wang, G. Y., Wang, J. H., and Li, H. L., Reciprocal effects of mesenchymal stem cells on experimental autoimmune encephalomyelitis is mediated by transforming growth factor-β and interleukin-6. Clin. Exp. Immunol., 158, 37–44 (2009).PubMedCrossRefGoogle Scholar
  48. Mannon, P. J., Remestemcel-L: human mesenchymal stem cells as an emerging therapy for Crohn’s disease. Expert Opin. Biol. Ther., 11, 1249–1256 (2011).PubMedCrossRefGoogle Scholar
  49. Martinez, F. O., Helming, L., and Gordon, S., Alternative activation of macrophages: An immunologic functional perspective. Annu. Rev. Immunol., 27, 451–483 (2009).PubMedCrossRefGoogle Scholar
  50. Menasche, P., Hagege, A. A., Vilquin, J. T., Desnos, M., Abergel, E., Pouzet, B., Bel, A., Sarateanu, S., Scorsin, M., and Schwartz, K., Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J. Am. Coll. Cardiol. 41, 1078–1083 (2003).PubMedCrossRefGoogle Scholar
  51. Menzies, F. M., Henriquez, F. L., Alexander, J., and Roberts, C. W., Sequential expression of macrophage antimicrobial/inflammatory and wound healing markers following innate, alternative and classical activation. Clin. Exp. Immunol., 160, 369–379 (2010).PubMedCrossRefGoogle Scholar
  52. Minguell, J. J. and Erices, A., Mesenchymal stem cells and the treatment of cardiac disease. Exp. Biol. Med. (Maywood), 231, 39–49 (2006).Google Scholar
  53. Nauta, A. J. and Fibbe, W. E., Immunomodulatory properties of mesenchymal stromal cells. Blood, 110, 3499–3506 (2007).PubMedCrossRefGoogle Scholar
  54. Németh, K., Leelahavanichkul, A., Yuen, P. S., Mayer, B., Parmelee, A., Doi, K., Robey, P. G., Leelahavanichkul, K., Koller, B. H., Brown, J. M., Hu, X., Jelinek, I., Star, R. A., and Mezey, E., Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat. Med., 15, 42–49 (2009).PubMedCrossRefGoogle Scholar
  55. Neuhuber, B., Timothy Himes, B., Shumsky, J. S., Gallo, G., and Fischer, I., Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Res., 1035, 73–85 (2005).PubMedCrossRefGoogle Scholar
  56. Niess, H., Bao, Q., Conrad, C., Zischek, C., Notohamiprodjo, M., Schwab, F., Schwarz, B., Huss, R., Jauch, K. W., Nelson, P. J., and Bruns, C. J., Selective targeting of genetically engineered mesenchymal stem cells to tumor stroma microenvironments using tissue-specific suicide gene expression suppresses growth of hepatocellular carcinoma. Ann. Surg., 254, 767–775 (2011).PubMedCrossRefGoogle Scholar
  57. Oh, J. Y., Kim, M. K., Shin, M. S., Wee, W. R., and Lee, J. H., Cytokine secretion by human mesenchymal stem cells cocultured with damaged corneal epithelial cells. Cytokine, 46, 100–103 (2009).PubMedCrossRefGoogle Scholar
  58. Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S. M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B., Bodine, D. M., Leri, A., and Anversa, P., Bone marrow cells regenerate infracted myocardium. Nature, 410, 701–705 (2001).PubMedCrossRefGoogle Scholar
  59. Ortiz, L. A., Gambelli, F., McBride, C., Gaupp, D., Baddoo, M., Kaminski, N., and Phinney, D. G., Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effect. Proc. Natl. Acad. Sci. U. S. A., 100, 8407–8411 (2003).PubMedCrossRefGoogle Scholar
  60. Otani, A., Dorrell, M. I., Kinder, K., Moreno, S. K., Nusinowitz, S., Banin, E., Heckenlively, J., and Friedlander, M., Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J. Clin. Invest., 114, 765–774 (2004).PubMedGoogle Scholar
  61. Perin, E. C., Dohmann, H. F., Borojevic, R., Silva, S. A., Sousa, A. L., Mesquita, C. T., Rossi, M. I., Carvalho, A. C., Dutra, H. S., and Dohmann, H. J., Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation, 107, 2294–2302 (2003).PubMedCrossRefGoogle Scholar
  62. Pitchford, S. C., Furze, R. C., Jones, C. P., Wengner, A. M., and Rankin, S. M., Differential mobilization of subsets of progenitor cells from the bone marrow. Cell Stem Cell, 4, 62–72 (2009).PubMedCrossRefGoogle Scholar
  63. Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., and Marshak, D. R., Multilieage potential of adult human mesenchymal stem cells. Science, 284, 143–147 (1999).PubMedCrossRefGoogle Scholar
  64. Pittenger, M. F. and Martin, B. J., Mesenchymal stem cells and their potential as cardiac therapeutics. Circ. Res., 95, 9–20 (2004).PubMedCrossRefGoogle Scholar
  65. Reagan, M. R. and Ghobrial, I. M., Multiple myelomamesenchymal stem cells: characterization, origin, and tumor-promoting effects. Clin. Cancer Res., 18, 342–349 (2012).PubMedCrossRefGoogle Scholar
  66. Rochefort, G. Y., Delorme, B., Lopez, A., Hérault, O., Bonnet, P., Charbord, P., Eder, V., and Domenech, J., Multipotential mesenchymal stem cells are mobilized into peripheral blood by hypoxia. Stem Cells, 24, 2202–2208 (2006).PubMedCrossRefGoogle Scholar
  67. Rojas, M., Xu, J., Woods, C. R., Mora, A. L., Spears, W., Roman, J., and Brigham, K. L., Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am. J. Respir. Cell Mol. Biol., 33, 145–152 (2005).PubMedCrossRefGoogle Scholar
  68. Roorda, B. D., ter Elst, A., Kamps, W. A., and de Bont, E. S., Bone marrow-derived cells and tumor growth: contribution of bone marrow-derived cells to tumor micro-environments with special focus on mesenchymal stem cells. Crit. Rev. Oncol. Hematol., 69, 187–198 (2009).PubMedCrossRefGoogle Scholar
  69. Rosová, I., Dao, M., Capoccia, B., Link, D., and Nolta, J. A., Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells, 26, 2173–2182 (2008).PubMedCrossRefGoogle Scholar
  70. Ryan, J. M., Barry, F., Murphy, J. M., and Mahon, B. P., Interferongamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin. Exp. Immunol., 149, 353–363 (2007).PubMedCrossRefGoogle Scholar
  71. Salem, H. K. and Thiemermann, C., Mesenchymal stromal cells: current understanding and clinical status. Stem Cells, 31, 585–596 (2010).Google Scholar
  72. Sanchez-Ramos, J., Song, S., Cardozo-Pelaez, F., Hazzi, C., Stedeford, T., Willing, A., Freeman, T. B., Saporta, S., Janssen, W., Patel, N., Cooper, D. R., and Sanberg, P. R., Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp. Neurol., 164, 247–256 (2000).PubMedCrossRefGoogle Scholar
  73. Sasaki, M., Abe, R., Fujita, Y., Ando, S., Inokuma, D., and Shimizu, H., Mesenchymal stem cells are recruited into wounded and contributed into wound repair by transdifferentiation into multiple skin cell type. J. Immunol., 180, 2581–2587 (2008).PubMedGoogle Scholar
  74. Sato, Y., Araki, H., Kato, J., Nakamura, K., Kawano, Y., Kobune, M., Sato, T., Miyanishi, K., Takayama, T., Takahashi, M., Takimoto, R., Iyama, S., Matsunaga, T., Ohtani, S., Matsuura, A., Hamada, H., and Niitsu, Y., Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood, 106, 756–763 (2005).PubMedCrossRefGoogle Scholar
  75. Savage, N. D., de Boer, T., Walburg, K. V., Joosten, S. A., van Meijgaarden, K., Geluk, A., and Ottenhoff, T. H., Human anti-inflammatory macrophages induce Foxp3+ GITR+ CD25+ regulatory T cells, which suppress via membranebound TGFbeta-1. J. Immunol., 181, 2220–2226 (2008).PubMedGoogle Scholar
  76. Selmani, Z., Naji, A., Zidi, I., Favier, B., Gaiffe, E., Obert, L., Borg, C., Saas, P., Tiberghien, P., Rouas-Freiss, N., Carosella, E. D., and Deschaseaux, F., Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFoxP3+ regulatory T cells. Stem Cells, 26, 212–222 (2008).PubMedCrossRefGoogle Scholar
  77. Seo, B. M., Miura, M., Gronthos, S., Bartold, P. M., Batouli, S., Brahim, J., Young, M., Robey, P. G., Wang, C. Y., and Shi, S., Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet, 364, 149–155 (2004).PubMedCrossRefGoogle Scholar
  78. Shi, Q., Bhattacharya, V., Hong-De Wu, M., and Sauvage, L. R., Utilizing granulocyte colony-stimulating factor to enhance vascular graft endothelialization from circulating blood cells. Ann. Vasc. Surg., 16, 314–320 (2002).PubMedCrossRefGoogle Scholar
  79. Singh, T., Prabhakar, S., Gupta, A., and Anand, A., Recruitment of stem cells into the injured retina after laser injury. Stem Cells Dev., 21, 448–454 (2012).PubMedCrossRefGoogle Scholar
  80. Spaggiari, G. M., Capobianco, A., Becchetti, S., Mingari, M. C., and Moretta, L., Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood, 107, 1484–1490 (2006).PubMedCrossRefGoogle Scholar
  81. Spaggiari, G. M., Capobianco, A., Abdelrazik, H., Becchetti, F., Mingari, M. C., and Moretta, L., Mesenchymal stem cells inhibit natural killer cell proliferation, cytotoxicity, and cytokine production: Role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood, 111, 1327–1333 (2008).PubMedCrossRefGoogle Scholar
  82. Spaggiari, G. M., Abdelrazik, H., Becchetti, F., and Moretta, L., MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: Central role of MSC-derived prostaglandin E2. Blood, 113, 6576–6583 (2009).PubMedCrossRefGoogle Scholar
  83. Strauer, B. E., Brehm, M., Zeus, T., Kostering, M., Hernandez, A., Sorg, R. V., Kogler, G., and Wernet, P., Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation, 106, 1913–1918 (2002).PubMedCrossRefGoogle Scholar
  84. Tohill, M., Mantovani, C., Wiberg, M., and Terenghi, G., Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regenratation. Neurosci. Lett., 362, 200–203 (2004).PubMedCrossRefGoogle Scholar
  85. Toma, C., Pittenger, M. F., Cahill, K. S., Byrne, B. J., and Kessler, P. D., Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in adult murine heart. Circulation, 105, 93–98 (2002).PubMedCrossRefGoogle Scholar
  86. Trinchieri, G., Biology of natural killer cells. Adv. Immunol., 47, 187–376 (1989).PubMedCrossRefGoogle Scholar
  87. Uccelli, A., Moretta, L., and Pistoia, V., Mesenchymal stem cells in health and disease. Nat. Rev. Immunol., 8, 726–736 (2008).PubMedCrossRefGoogle Scholar
  88. Vossmerbaeumer, U., Ohnesorge, S., Kuehl, S., Haapalahti, M., Kluter, H., Jonas, J. B., Thierse, H. J., and Bieback, K., Retinal pigment epithelial phenotype induced in human adipose tissue-derived mesenchymal stromal cells. Cytotherapy, 11, 177–188 (2009).PubMedCrossRefGoogle Scholar
  89. Weaver, C. T., Hatton, R. D., Mangan, P. R., and Harrington, L. E., IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu. Rev. Immunol., 25, 821–852 (2007).PubMedCrossRefGoogle Scholar
  90. Wu, Y., Chen, L., Scott, P. G., and Tredget, E. E., Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells, 25, 2648–2659 (2007).PubMedCrossRefGoogle Scholar
  91. Xu, W., Zhang, X., Qian, H., Zhu, W., Sun, X., Hu, J., Zhou, H., and Chen, Y., Mesenchymal stem cells from adult human bone marrow differentiate into a cardiomyocyte phenotype in vitro. Exp. Biol. Med. (Maywood), 229, 623–631 (2004).Google Scholar
  92. Yilmaz, G., Alexander, J. S., Erkuran Yilmaz, C., and Granger, D. N., Induction of neuro-protective/regenerative genes in stem cells infiltrating post-ischemic brain tissue. Exp. Transl. Stroke Med., 2, 11 (2010).PubMedCrossRefGoogle Scholar
  93. Yoon, Y. S., Wecker, A., Heyd, L., Park, J. S., Tkebuchava, T., Kusano, K., Hanley, A., Scadova, H., Qin, G., Cha, D. H., Johnson, K. L., Aikawa, R., Asahara, T., and Losordo, D. W., Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J. Clin. Invest., 115, 326–338 (2005).PubMedGoogle Scholar
  94. Yoshikawa, T., Mitsuno, H., Nonaka, I., Sen, Y., Kawanishi, K., Inada, Y., Takakura, Y., Okuchi, K., and Nonomura, A., Wound therapy by marrow mesenchymal cell transplantation. Plast. Reconstr. Surg., 121, 860–877 (2008).PubMedCrossRefGoogle Scholar
  95. Zanone, M. M., Favaro, E., Miceli, I., Grassi, G., Camussi, E., Caorsi, C., Amoroso, A., Giovarelli, M., Perin, P. C., and Camussi, G., Human mesenchymal stem cells modulate cellular immune response to islet antigen glutamic acid decarboxylase in type 1 diabetes. J. Clin. Endocrinol. Metab., 95, 3788–3797 (2010).PubMedCrossRefGoogle Scholar
  96. Zavan, B., Michelotto, L., Lancerotto, L., Della Puppa, A., D’Avella, D., Abatangelo, G., Vindigni, V., and Cortivo, R., Neural potential of a stem cell population in the adipose and cutaneous tissues. Neurol. Res., 32, 47–54 (2010).PubMedCrossRefGoogle Scholar
  97. Zhang, Q., Shi, S., Liu, Y., Uyanne, J., Shi, Y., Shi, S., and Le, A. D., Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J. Immunol., 183, 7787–7798 (2009).PubMedCrossRefGoogle Scholar
  98. Zhang, Q. Z., Su, W. R., Shi, S. H., Wilder-Smith, P., Xiang, A. P., Wong, A., Nguyen, A. L., Kwon, C. W., and Le, A. D., Human Gingiva-Derived Mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing. Stem Cells, 28, 1856–1868 (2010).PubMedCrossRefGoogle Scholar
  99. Zhang, Z. G., Zhang, L., Croll, S. D., and Chopp, M., Angiopoietin-1 reduces cerebral blood vessel leakage and ischemic lesion volume after focal cerebral embolic ischemia in mice. Neuroscience, 113, 683–687 (2002).PubMedCrossRefGoogle Scholar
  100. Zimmet, J. M. and Hare, J. M., Emerging role for bone marrow derived mesenchymal stem cells in myocardial regenerative therapy. Basic Res. Cardiol., 100, 471–481 (2005).PubMedCrossRefGoogle Scholar
  101. Zuk, P. A., Zhu, M., Ashjian, P., De Ugarte, D. A., Huang, J. I., Mizuno, H., Alfonso, Z. C., Fraser, J. K., Benhaim, P., and Hedrick, M. H., Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell, 13, 4279–4295 (2002).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2012

Authors and Affiliations

  • Hyun Sook Hong
    • 1
  • Yeong Hoon Kim
    • 2
  • Youngsook Son
    • 1
    • 3
    Email author
  1. 1.Department of Genetic Engineering & Graduate School of BiotechnologyKyung Hee UniversityYonginKorea
  2. 2.Department of Ophthalmology, College of MedicineThe Catholic University of Korea, St. Paul’s HospitalSeoulKorea
  3. 3.Department of Genetic Engineering, College of Life ScienceKyung Hee UniversityYonginKorea

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