Abstract
Mesenchymal stromal/stem cells (MSCs) were originally isolated from bone marrow (BM), but are now known to be present in all fetal and adult tissues. These multipotent cells can be differentiated into at least three downstream mesenchymal lineages that include bone, cartilage, and fat. However, under some experimental conditions, these cells can differentiate into nonmesenchymal cell types and/or participate in regeneration of damaged tissues through a variety of mechanisms. Most recently, MSCs have been derived from human embryonic stem cells (hESCs) through several different methodologies. Human MSCs derived from hESCs have been shown to possess characteristics very similar to BM-derived MSCs. Thus, the generation of MSCs from hESCs provides an opportunity to study the developmental biology of cells of mesenchymal lineages in an appropriate in vitro model. Furthermore, MSCs from different adult tissue sources are being actively investigated in a multitude of clinical trials; therefore, hESCs could provide an unlimited source of MSCs for potential clinical applications in the future. Such MSCs could be used without further differentiation for regeneration of tissues, or they could be directed towards specific lineage pathways, such as bone and cartilage, for reconstruction of tissues. Finally, immunomodulatory properties of hESC-derived MSCs are likely to prove valuable for inducing immune tolerance toward other cells or tissues derived from the same hESC lines.
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References
Friedenstein, A. J., Petrakova, K. V., Kurolesova, A. I., and Frolova, G. P. (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 6, 230–247.
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., et al. (1999) Multilineage potential of adult human mesenchymal stem cells. Science. 284, 143–147.
Zuk, P. A., Zhu, M., Mizuno, H., Huang, J., Futrell, J. W., Katz, A. J., et al. (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7, 211–228.
Williams, J. T., Southerland, S. S., Souza, J., Calcutt, A. F., and Cartledge, R. G. (1999) Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. Am. Surg. 65, 22–26.
De Bari, C., Dell’Accio, F., Tylzanowski, P., and Luyten, F. P. (2001) Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 44, 1928–1942.
Gronthos, S., Mankani, M., Brahim, J., Robey, P. G., and Shi, S. (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl. Acad. Sci. USA. 97, 13625–13630.
Hoogduijn, M. J., Crop, M. J., Peeters, A. M., Van Osch, G. J., Balk, A. H., Ijzermans, J. N., et al. (2007) Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells Dev. 16, 597–604.
In ’t Anker, P. S., Scherjon, S. A., Kleijburg-van der Keur, C., de Groot-Swings, G. M., Claas, F. H., Fibbe, W. E., et al. (2004) Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells. 22, 1338–1345.
In ’t Anker, P. S., Scherjon, S. A., Kleijburg-van der Keur, C., Noort, W. A., Claas, F. H., Willemze, R., Fibbe, W. E., et al. (2003) Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood. 102, 1548–1549.
Bieback, K., Kern, S., Kluter, H., and Eichler, H. (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells. 22, 625–634.
Campagnoli, C., Roberts, I. A., Kumar, S., Bennett, P. R., Bellantuono, I., and Fisk, N. M. (2001) Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 98, 2396–2402.
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., et al. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 8, 315–317.
Xu, C., Jiang, J., Sottile, V., McWhir, J., Lebkowski, J., and Carpenter, M. K. (2004) Immortalized fibroblast-like cells derived from human embryonic stem cells support undifferentiated cell growth. Stem Cells. 22, 972–980.
Stojkovic, P., Lako, M., Stewart, R., Przyborski, S., Armstrong, L., Evans, J., et al. (2005) An autogeneic feeder cell system that efficiently supports growth of undifferentiated human embryonic stem cells. Stem Cells. 23, 306–314.
Wang, Q., Fang, Z. F., Jin, F., Lu, Y., Gai, H., and Sheng, H. Z. (2005) Derivation and growing human embryonic stem cells on feeders derived from themselves. Stem Cells. 23, 1221–1227.
Yoo, S. J., Yoon, B. S., Kim, J. M., Song, J. M., Roh, S., You, S., and Yoon, H. S. (2005) Efficient culture system for human embryonic stem cells using autologous human embryonic stem cell-derived feeder cells. Exp. Mol. Med. 37, 399–407.
Barberi, T., Willis, L. M., Socci, N. D., and Studer, L. (2005) Derivation of multipotent mesenchymal precursors from human embryonic stem cells. PLoS Med. 2, e161.
Trivedi, P. and Hematti, P. (2007) Simultaneous generation of CD34(+) primitive hematopoietic cells and CD73(+) mesenchymal stem cells from human embryonic stem cells cocultured with murine OP9 stromal cells. Exp. Hematol. 35, 146–154.
Olivier, E. N., Rybicki, A. C., and Bouhassira, E. E. (2006) Differentiation of human embryonic stem cells into bipotent mesenchymal stem cells. Stem Cells. 24, 1914–1922.
Lian, Q., Lye, E., Suan Yeo, K., Khia Way Tan, E., Salto-Tellez, M., Liu, T. M., et al. (2007) Derivation of clinically compliant MSCs from CD105+, CD24− differentiated human ESCs. Stem Cells. 25, 425–436.
Trivedi, P. and Hematti, P. (2008) Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells. Exp. Hematol. 36, 350–359.
Hwang, N. S., Varghese, S., Zhang, Z., and Elisseeff, J. (2006) Chondrogenic differentiation of human embryonic stem cell-derived cells in arginine-glycine-aspartate-modified hydrogels. Tissue Eng. 12, 2695–2706.
Hwang, N. S., Varghese, S., Lee, H. J., Zhang, Z., Ye, Z., Bae, J., et al. (2008) In vivo commitment and functional tissue regeneration using human embryonic stem cell-derived mesenchymal cells. Proc. Natl. Acad. Sci.USA. 105, 20641–20646.
Bendall, S. C., Stewart, M. H., Menendez, P., George, D., Vijayaragavan, K., Werbowetski-Ogilvie, T., et al. (2007) IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro. Nature. 448, 1015–1021.
Barberi, T., Bradbury, M., Dincer, Z., Panagiotakos, G., Socci, N. D., and Studer, L. (2007) Derivation of engraftable skeletal myoblasts from human embryonic stem cells. Nat. Med. 13, 642–648.
Lee, G., Kim, H., Elkabetz, Y., Al Shamy, G., Panagiotakos, G., Barberi, T., et al. (2007) Isolation and directed differentiation of neural crest stem cells derived from human embryonic stem cells. Nat. Biotechnol. 25, 1468–1475.
Gang, E. J., Bosnakovski, D., Figueiredo, C. A., Visser, J. W., and Perlingeiro, R. C. (2007) SSEA-4 identifies mesenchymal stem cells from bone marrow. Blood. 109, 1743–1751.
Cheng, L., Hammond, H., Ye, Z., Zhan, X., and Dravid, G. (2003) Human adult marrow cells support prolonged expansion of human embryonic stem cells in culture. Stem Cells. 21, 131–142.
Wagner, W., Wein, F., Seckinger, A., Frankhauser, M., Wirkner, U., Krause, U., et al. (2005) Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp. Hematol. 33, 1402–1416.
Karp, J. M., Ferreira, L. S., Khademhosseini, A. H., Kwon, A., Yeh, J., and Langer, R. S. (2006) Cultivation of human embryonic stem cells without the embryoid body step enhances osteogenesis in vitro. Stem Cells. 24, 835–843.
Cao, T., Heng, B. C., Ye, C. P., Liu, H., Toh, W. S., Robson, P., et al. (2005) Osteogenic differentiation within intact human embryoid bodies result in a marked increase in osteocalcin secretion after 12 days of in vitro culture, and formation of morphologically distinct nodule-like structures. Tissue Cell. 37, 325–334.
Woll, N. L., Heaney, J. D., and Bronson, S. K. (2006) Osteogenic nodule formation from single embryonic stem cell-derived progenitors. Stem Cells Dev. 15, 865–879.
Bielby, R. C., Boccaccini, A. R., Polak, J. M., and Buttery, L. D. (2004) In vitro differentiation and in vivo mineralization of osteogenic cells derived from human embryonic stem cells. Tissue Eng. 10, 1518–1525.
Toh, W. S., Yang, Z., Liu, H., Heng, B. C., Lee, E. H., and Cao, T. (2007) Effects of culture conditions and bone morphogenetic protein 2 on extent of chondrogenesis from human embryonic stem cells. Stem Cells. 25, 950–960.
Sottile, V., Thomson, A., and McWhir, J. (2003) In vitro osteogenic differentiation of human ES cells. Cloning Stem Cells. 5, 149–155.
Alsberg, E., von Recum, H. A., and Mahoney, M. J. (2006) Environmental cues to guide stem cell fate decision for tissue engineering applications. Expert Opin. Biol. Ther. 6, 847–866.
Makino, S., Fukuda, K., Miyoshi, S., Konishi, F., Kodama, H., Pan, J., et al. (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J. Clin. Invest. 103, 697–705.
Oswald, J., Boxberger, S., Jorgensen, B., Feldmann, S., Ehninger, G., Bornhauser, M., et al. (2004) Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells. 22, 377–384.
Spees, J. L., Olson, S. D., Ylostalo, J., Lynch, P. J., Smith, J., Perry, A., et al. (2003) Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proc. Natl. Acad. Sci. USA. 100, 2397–2402.
Schwartz, R. E., Reyes, M., Koodie, L., Jiang, Y., Blackstad M., Lund, T., et al. (2002) Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J. Clin. Invest. 109, 1291–1302.
Woodbury, D., Schwarz, E. J., Prockop, D. J., and Black, I. B. (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J. Neurosci. Res. 61, 364–370.
Tang, D. Q., Cao, L. Z., Burkhardt, B. R., Xia, C. Q., Litherland, S. A., Atkinson, M. A., et al. (2004) In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes. 53, 1721–1732.
Phinney, D. G. and Prockop, D. J. (2007) Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair–current views. Stem Cells. 25, 2896–2902.
Prockop, D. J. (2007) “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clin. Pharmacol. Ther. 82, 241–243.
Chamberlain, G., Fox, J., Ashton, B., and Middleton, J. (2007) Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 25, 2739–2749.
Caplan, A. I. (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J. Cell Physiol. 213, 341–347.
Keating, A. (2006) Mesenchymal stromal cells. Curr. Opin. Hematol. 13, 419–425.
Deans, R. J. and Moseley, A. B. (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp. Hematol. 28, 875–884.
Dazzi, F. and Horwood, N. J. (2007) Potential of mesenchymal stem cell therapy. Curr. Opin. Oncol. 19, 650–655.
Uccelli, A., Pistoia, V., and Moretta, L. (2007) Mesenchymal stem cells: a new strategy for immunosuppression? Trends Immunol. 28, 219–226.
Koc, O. N., Day, J., Nieder, M., Gerson, S. L., Lazarus, H. M., and Krivit, W. (2002) Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant. 30, 215–222.
Horwitz, E. M., Prockop, D. J., Fitzpatrick, L. A., Koo, W. W., Gordon, P. L., Neel, M., et al. (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat. Med. 5, 309–313.
Chen, S. L., Fang, W. W., Ye, F., Liu, Y. H., Qian, J., Shan, S. J., et al. (2004) Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am. J. Cardiol. 94, 92–95.
Mazzini, L., Mareschi, K., Ferrero, I., Vassallo, E., Oliveri, G., Boccaletti, R., et al. (2006) Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis. Neurol. Res. 28, 523–526.
Le Blanc, K., Frassoni, F., Ball, L., Locatelli, F., Roelofs, H., Lewis, I., et al. (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 371, 1579–1586.
Taupin, P. (2006) OTI-010 Osiris Therapeutics/JCR Pharmaceuticals. Curr. Opin. Invest. Drugs. 7, 473–481.
Le Blanc, K. and Ringden, O. (2005) Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. 11, 321–334.
Stagg, J. and Galipeau, J. (2007) Immune plasticity of bone marrow-derived mesenchymal stromal cells. Handb. Exp. Pharmacol. 180, 45–66.
Noel, D., Djouad, F., Bouffi, C., Mrugala, D., and Jorgensen, C. (2007) Multipotent mesenchymal stromal cells and immune tolerance. Leuk. Lymphoma. 48, 1283–1289.
Nauta, A. J. and Fibbe, W. E. (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood. 110, 3499–3506.
Giordano, A., Galderisi, U., and Marino, I. R. (2007) From the laboratory bench to the patient’s bedside: an update on clinical trials with mesenchymal stem cells. J. Cell Physiol. 211, 27–35.
Le Blanc, K., Tammik, C., Rosendahl, K., Zetterberg, E., and Ringden, O. (2003) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp. Hematol. 31, 890–896.
Yen, B. L., Chang, C. J., Liu, K. J., Chen, Y. C., Hu, H. I., Bai, C. H., and Yen, M. L. (2009) Brief report – human embryonic stem cell-derived mesenchymal progenitors possess strong immunosuppressive effects toward natural killer cells as well as T lymphocytes. Stem Cells. 27, 451–456.
Yamanaka, S. (2007) Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell. 1, 39–49.
Dieterle, C. D., Hierl, F. X., Gutt, B., Arbogast, H., Meier, G. R., Veitenhansl, M., Hoffmann, J. N., and Landgraf, R. (2005) Insulin and islet autoantibodies after pancreas transplantation. Transpl. Int. 18, 1361–1365.
Laughlin, E., Burke, G., Pugliese, A., Falk, B., and Nepom, G. (2008) Recurrence of autoreactive antigen-specific CD4+ T cells in autoimmune diabetes after pancreas transplantation. Clin. Immunol. 128, 23–30.
Thomson, J. A. and Odorico, J. S. (2000) Human embryonic stem cell and embryonic germ cell lines. Trends. Biotechnol. 18, 53–57.
Baker, M. (2008) FDA to vet embryonic stem cells’ safety. Nature. 452, 670.
Dihne, M., Bernreuther, C., Hagel, C., Wesche, K. O., and Schachner, M. (2006) Embryonic stem cell-derived neuronally committed precursor cells with reduced teratoma formation after transplantation into the lesioned adult mouse brain. Stem Cells. 24, 1458–1466.
Leor, J., Gerecht, S., Cohen, S., Miller, L., Holbova, R., Ziskind, A., Shachar, M., Feinberg, M. S, Guetta, E., and Itskovitz-Eldor, J. (2007) Human embryonic stem cell transplantation to repair the infarcted myocardium. Heart. 93, 1278–1284.
Cai, J., Yi, F. F., Yang, X. C., Lin, G. S., Jiang, H., Wang, T., et al. (2007) Transplantation of embryonic stem cell-derived cardiomyocytes improves cardiac function in infarcted rat hearts. Cytotherapy. 9, 283–291.
Arnhold, S., Klein, H., Semkova, I., Addicks, K., and Schraermeyer, U. (2004) Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space. Invest. Ophthalmol. Vis. Sci. 45, 4251–4255.
Rubio, D., Garcia-Castro, J., Martin, M. C., de la Fuente, R., Cigudosa, J. C., Lloyd, A. C., et al. (2005) Spontaneous human adult stem cell transformation. Cancer Res. 65, 3035–3039.
Wang, Y., Huso, D. L., Harrington, J., Kellner, J., Jeong, D. K., Turney, J., et al. (2005) Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture. Cytotherapy. 7, 509–519.
Tolar, J., Nauta, A. J., Osborn, M. J., Panoskaltsis Mortari, A., McElmurry, R. T., Bell, S., et al. (2007) Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 25, 371–379.
Djouad, F., Plence, P., Bony, C., Tropel, P., Apparailly, F., Sany, J., et al. (2003) Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood. 102, 3837–3844.
Karnoub, A. E., Dash, A. B., Vo, A. P., Sullivan, A., Brooks, M. W., Bell, G. W., et al. (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 449, 557–563
Acknowledgment
I thank Dr. Laura H. Hogan for her critical review of the manuscript. The author is the recipient of NIH/NHLBI HL081076 K08 award.
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Hematti, P. (2011). Human Embryonic Stem Cell-Derived Mesenchymal Progenitors: An Overview. In: Nieden, N. (eds) Embryonic Stem Cell Therapy for Osteo-Degenerative Diseases. Methods in Molecular Biology, vol 690. Humana Press. https://doi.org/10.1007/978-1-60761-962-8_11
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