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Mesenchymal Stem Cell Preparations—Comparing Apples and Oranges

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Abstract

Mesenchymal stem cells (MSC) represent a type of adult stem cells that can easily be isolated from various tissues and expanded in vitro. Past reports on their pluripotency and possible clinical applications have raised hopes and interest in MSC. Multiple designations have been given to different MSC preparations. So far MSC are poorly defined by a combination of physical, phenotypical and functional properties. As MSC could be derived from different tissues as starting material, by diverse isolation protocols, cultured and expanded in different media and conditions, the MSC preparations from different laboratories are highly heterogeneous. All of these variables might have implications (1) on the selection of cell types and the composition of heterogeneous subpopulations; (2) they can selectively favor expansion of different cell populations with totally different potentials; or (3) they might alter the long term fate of adult stem cells upon in vitro culture. The recent controversy on the multilineage differentiation potentials of some specific MSC preparations might be attributed to this lack of common standards. More precise molecular and cellular markers to define subsets of MSC and to standardize the protocols for expansion of MSC are urgently needed.

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Reference

  1. Dominici, M., Le Blanc, K., Mueller, I., et al. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315–317.

    Article  PubMed  CAS  Google Scholar 

  2. Wagner, W., Wein, F., Seckinger, A., et al. (2005). Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Experimental Hematology, 33, 1402–1416.

    Article  PubMed  CAS  Google Scholar 

  3. Caplan, A. I. (1991). Mesenchymal stem cells. Journal of Orthopaedic Research, 9, 641–650.

    Article  PubMed  CAS  Google Scholar 

  4. Friedenstein, A. J., Petrakova, K. V., Kurolesova, A. I., & Frolova, G. P. (1968). Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation, 6, 230–247.

    Article  PubMed  CAS  Google Scholar 

  5. Friedenstein, A. J., Chailakhyan, R. K., Latsinik, N. V., Panasyuk, A. F., & Keiliss-Borok, I. V. (1974). Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation, 17, 331–340.

    Article  PubMed  CAS  Google Scholar 

  6. Nakahara, H., Bruder, S. P., Haynesworth, S. E., et al. (1990). Bone and cartilage formation in diffusion chambers by subcultured cells derived from the periosteum. Bone, 11, 181–188.

    Article  PubMed  CAS  Google Scholar 

  7. Horwitz, E. M., & Keating A. (2000). Nonhematopoietic mesenchymal stem cells: What are they? Cytotherapy, 2, 387–388.

    Article  PubMed  CAS  Google Scholar 

  8. Horwitz, E. M., Le, B. K., Dominici, M., et al. (2005). Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy, 7, 393–395.

    Article  PubMed  CAS  Google Scholar 

  9. Erices, A., Conget, P., & Minguell, J. J. (2000). Mesenchymal progenitor cells in human umbilical cord blood. British Journal of Haematology, 109, 235–242.

    Article  PubMed  CAS  Google Scholar 

  10. Johnstone, B., Hering, T. M., Caplan, A. I., Goldberg, V. M., & Yoo, J. U. (1998). In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Experimental Cell Research, 238, 265–272.

    Article  PubMed  CAS  Google Scholar 

  11. Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418, 41–49.

    Article  PubMed  CAS  Google Scholar 

  12. Kogler, G., Sensken, S., Airey, J. A., et al. (2004). A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. Journal of Experimental Medicine, 200, 123–135.

    Article  PubMed  Google Scholar 

  13. Reyes, M., Lund, T., Lenvik, T., Aguiar, D., Koodie, L., & Verfaillie, C. M. (2001). Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood, 98, 2615–2625.

    Article  PubMed  CAS  Google Scholar 

  14. Petersen, B. E., Bowen, W. C., Patrene, K. D., et al. (1999). Bone marrow as a potential source of hepatic oval cells. Science, 284, 1168–1170.

    Article  PubMed  CAS  Google Scholar 

  15. Schwartz, R. E., Reyes, M., Koodie, L., et al. (2002). Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. Journal of Clinical Investigation, 109, 1291–1302.

    Article  PubMed  CAS  Google Scholar 

  16. Bjornson, C. R., Rietze, R. L., Reynolds, B. A., Magli, M. C., & Vescovi, A. L. (1999). Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science, 283, 534–537.

    Article  PubMed  CAS  Google Scholar 

  17. Mezey, E., Chandross, K. J., Harta, G., Maki, R. A., & McKercher, S. R. (2000). Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science, 290, 1779–1782.

    Article  PubMed  CAS  Google Scholar 

  18. Ying, Q. L., Nichols, J., Evans, E. P., & Smith, A. G. (2002). Changing potency by spontaneous fusion. Nature, 416, 545–548.

    Article  PubMed  CAS  Google Scholar 

  19. Terada, N., Hamazaki, T., Oka, M., et al. (2002). Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature, 416, 542–545.

    Article  PubMed  CAS  Google Scholar 

  20. Jiang, Y., Vaessen, B., Lenvik, T., Blackstad, M., Reyes, M., & Verfaillie, C. M. (2002). Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Experimental Hematology, 30, 896–904.

    Article  PubMed  CAS  Google Scholar 

  21. Zeng, L., Rahrmann, E., Hu, Q., et al. (2006). Multipotent adult progenitor cells from swine bone marrow. Stem Cells, 24, 2355–2366.

    Article  PubMed  CAS  Google Scholar 

  22. Jiang, Y., Henderson, D., Blackstad, M., Chen, A., Miller, R. F., & Verfaillie, C. M. (2003). Neuroectodermal differentiation from mouse multipotent adult progenitor cells. Proceedings of the National Academy of Sciences of the United States of America, 100(Suppl 1), 11854–11860.

    Article  PubMed  CAS  Google Scholar 

  23. Serafini, M., Dylla, S. J., Oki, M., et al. (2007). Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells. Journal of Experimental Medicine, 204, 129–139.

    Article  PubMed  CAS  Google Scholar 

  24. Hochedlinger, K., & Jaenisch, R. (2006). Nuclear reprogramming and pluripotency. Nature, 441, 1061–1067.

    Article  PubMed  CAS  Google Scholar 

  25. Morshead, C. M., Benveniste, P., Iscove, N. N., & van der, Kooy, D. (2002). Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations. Nature Medicine, 8, 268–273.

    Article  PubMed  CAS  Google Scholar 

  26. Raedt, R., Pinxteren, J., Van Dycke, A., et al. (2007). Differentiation assays of bone marrow-derived Multipotent Adult Progenitor Cell (MAPC)-like cells towards neural cells cannot depend on morphology and a limited set of neural markers. Experimental Neurology, 203, 542–554.

    Article  PubMed  CAS  Google Scholar 

  27. Wagner, W., Roderburg, C., Wein, F., et al. (2007). Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors. Stem Cells 2007.

  28. Simmons, P. J., & Torok-Storb, B. (1991). Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood, 78, 55–62.

    PubMed  CAS  Google Scholar 

  29. Quirici, N., Soligo, D., Bossolasco, P., Servida, F., Lumini, C., & Deliliers, G. L. (2002). Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Experimental Hematology, 30, 783–791.

    Article  PubMed  CAS  Google Scholar 

  30. Sabatini, F., Petecchia, L., Tavian, M., Jodon, d. V. V, Rossi, G. A., & Brouty-Boye, D. (2005). Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Laboratory Investigation, 85, 962–971.

    Article  PubMed  CAS  Google Scholar 

  31. Buhring, H. J., Battula, V. L., Treml, S., Schewe, B., Kanz, L., & Vogel, W. (2007). Novel markers for the prospective isolation of human MSC. Annals of the New York Academy of Sciences, 2007.

  32. Pittenger, M. F., Mackay, A. M., Beck, S. C., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143–147.

    Article  PubMed  CAS  Google Scholar 

  33. Wagner, W., Feldmann, R. E., Jr., Seckinger, A., et al. (2006). The heterogeneity of human mesenchymal stem cell preparations—Evidence from simultaneous analysis of proteomes and transcriptomes. Experimental Hematology, 34, 536–548.

    Article  PubMed  CAS  Google Scholar 

  34. Colter, D. C., Sekiya, I., & Prockop, D. J. (2001). Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proceedings of the National Academy of Sciences of the United States of America, 98, 7841–7845.

    Article  PubMed  CAS  Google Scholar 

  35. Javazon, E. H., Colter, D. C., Schwarz, E. J., & Prockop, D. J. (2001). Rat marrow stromal cells are more sensitive to plating density and expand more rapidly from single-cell-derived colonies than human marrow stromal cells. Stem Cells, 19, 219–225.

    Article  PubMed  CAS  Google Scholar 

  36. Friedenstein, A. J., Piatetzky-Shapiro, I. I., & Petrakova, K. V. (1966). Osteogenesis in transplants of bone marrow cells. Journal of Embryology and Experimental Morphology, 16, 381–390.

    PubMed  CAS  Google Scholar 

  37. Zuk, P. A., Zhu, M., Mizuno, H., et al. (2001). Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Engineering, 7, 211–228.

    Article  PubMed  CAS  Google Scholar 

  38. Bieback, K., Kern, S., Kluter, H., & Eichler, H. (2004). Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells, 22, 625–634.

    Article  PubMed  Google Scholar 

  39. Kuznetsov, S. A., Mankani, M. H., Gronthos, S., Satomura, K., Bianco, P., & Robey, P. G. (2001). Circulating skeletal stem cells. Journal of Cell Biology, 153, 1133–1140.

    Article  PubMed  CAS  Google Scholar 

  40. da Silva, M. L., Chagastelles, P. C., & Nardi, N. B. (2006). Mesenchymal stem cells reside in virtually all post-natal organs and tissues. Journal of Cell Science, 119, 2204–2213.

    Article  Google Scholar 

  41. Kern, S., Eichler, H., Stoeve, J., Kluter, H., & Bieback, K. (2006). Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells, 24, 1294–1301.

    Article  PubMed  CAS  Google Scholar 

  42. Anderson, D. G., Levenberg, S., & Langer, R. (2004). Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells. Nature Biotechnology, 22, 863–866.

    Article  PubMed  CAS  Google Scholar 

  43. Engler, A. J., Sen, S., Sweeney, H. L., & Discher D. E. (2006). Matrix elasticity directs stem cell lineage specification. Cell, 126, 677–689.

    Article  PubMed  CAS  Google Scholar 

  44. Ren, H., Cao, Y., Zhao, Q., et al. (2006). Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochemical and Biophysical Research Communications, 347, 12–21.

    Article  PubMed  CAS  Google Scholar 

  45. Lange, C., Cakiroglu, F., Spiess, A. N., Cappallo-Obermann, H., Dierlamm, J., & Zander, A. R. (2007). Accelerated and safe expansion of human mesenchymal stromal cells in animal serum-free medium for transplantation and regenerative medicine. Journal of Cellular Physiology, 213, 18–26.

    Article  PubMed  CAS  Google Scholar 

  46. Muller, I., Kordowich, S., Holzwarth, C., et al. (2006). Animal serum-free culture conditions for isolation and expansion of multipotent mesenchymal stromal cells from human BM. Cytotherapy, 8, 437–444.

    Article  PubMed  CAS  Google Scholar 

  47. Stute, N., Holtz, K., Bubenheim, M., Lange, C., Blake, F., & Zander, A. R. (2004). Autologous serum for isolation and expansion of human mesenchymal stem cells for clinical use. Experimental Hematology, 32, 1212–1225.

    Article  PubMed  CAS  Google Scholar 

  48. Kocaoemer, A., Kern, S., Kluter, H., & Bieback, K. (2007). Human AB serum and thrombin-activated platelet-rich plasma are suitable alternatives to fetal calf serum for the expansion of mesenchymal stem cells from adipose tissue. Stem Cells, 25, 1270–1278.

    Article  PubMed  CAS  Google Scholar 

  49. DiGirolamo, C. M., Stokes, D., Colter, D., Phinney, D. G., Class, R., & Prockop, D. J. (1999). Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. British Journal of Haematology, 107, 275–281.

    Article  PubMed  CAS  Google Scholar 

  50. Fehrer, C., Laschober, G., & Lepperdinger, G. (2006). Aging of murine mesenchymal stem cells. Annals of the New York Academy of Sciences, 1067, 235–242.

    Article  PubMed  CAS  Google Scholar 

  51. Javazon, E. H., Beggs, K. J., & Flake, A. W. (2004). Mesenchymal stem cells: Paradoxes of passaging. Experimental Hematology, 32, 414–425.

    Article  PubMed  CAS  Google Scholar 

  52. Sotiropoulou, P. A., Perez, S. A., Salagianni, M., Baxevanis, C. N., & Papamichail, M. (2005). Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells, 24, 462–471.

    Article  PubMed  Google Scholar 

  53. Gregory, C. A., Singh, H., Perry, A. S., & Prockop, D. J. (2003). The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. Journal of Biological Chemistry, 278, 28067–28078.

    Article  PubMed  CAS  Google Scholar 

  54. Wang, H., & Scott, R. E. (1993). Inhibition of distinct steps in the adipocyte differentiation pathway in 3T3 T mesenchymal stem cells by dimethyl sulphoxide (DMSO). Cell Proliferation, 26, 55–66.

    PubMed  CAS  Google Scholar 

  55. Kotobuki, N., Hirose, M., Machida, H., et al. (2005). Viability and osteogenic potential of cryopreserved human bone marrow-derived mesenchymal cells. Tissue Engineering, 11, 663–673.

    Article  PubMed  CAS  Google Scholar 

  56. Wuchter, P., Boda-Heggemann, J., Straub, B. K., et al. (2007). Processus and recessus adhäerentes: Giant adherens cell junction systems connect and attract human mesenchymal stem cells. Cell Tissue Research, 328, 499–514.

    Article  PubMed  Google Scholar 

  57. Franke, W. W., Grund, C., Jackson, B. W., & Illmensee K. (1983). Formation of cytoskeletal elements during mouse embryogenesis. IV. Ultrastructure of primary mesenchymal cells and their cell–cell interactions. Differentiation, 25, 121–141.

    Article  PubMed  CAS  Google Scholar 

  58. Schofield, R. (1978). The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells, 4, 7–25.

    PubMed  CAS  Google Scholar 

  59. Ho, A. D., & Wagner, W. (2007). The beauty of asymmetry–asymmetric divisions and self-renewal in the hematopoietic system. Current Opinion in Hematology, 14, 330–336.

    Article  PubMed  Google Scholar 

  60. Wagner, W., Wein, F., Roderburg, C., et al. (2007). Adhesion of hematopoietic progenitor cells to human mesenchymal stem cells as a model for cell–cell interaction. Experimental Hematology, 35, 314–325.

    Article  PubMed  CAS  Google Scholar 

  61. Gottschling, S., Saffrich, R., Seckinger, A., et al. (2007). Human mesenchymal stroma cells regulate initial self-renewing divisions of hematopoietic progenitor cells by a beta1-integrin-dependent mechanism. Stem Cells, 25, 798–806.

    Article  PubMed  CAS  Google Scholar 

  62. Zhang, J., Niu, C., Ye, L., et al. (2003). Identification of the haematopoietic stem cell niche and control of the niche size. Nature, 425, 836–841.

    Article  PubMed  CAS  Google Scholar 

  63. Wilson, A., & Trumpp, A. (2006). Bone-marrow haematopoietic-stem-cell niches. Nature Reviews. Immunology, 6, 93–106.

    Article  PubMed  CAS  Google Scholar 

  64. Forsberg, E. C., Prohaska, S. S., Katzman, S., Heffner, G. C., Stuart, J. M., & Weissman, I. L. (2005). Differential expression of novel potential regulators in hematopoietic stem cells. PLoS Genet, 1, e28.

    Article  PubMed  Google Scholar 

  65. Wineman, J., Moore, K., Lemischka, I., & Muller-Sieburg, C. (1996). Functional heterogeneity of the hematopoietic microenvironment: Rare stromal elements maintain long-term repopulating stem cells. Blood, 87, 4082–4090.

    PubMed  CAS  Google Scholar 

  66. Gan, O. I., Murdoch, B., Larochelle, A., & Dick, J. E. (1997). Differential maintenance of primitive human SCID-repopulating cells, clonogenic progenitors, and long-term culture-initiating cells after incubation on human bone marrow stromal cells. Blood, 90, 641–650.

    PubMed  CAS  Google Scholar 

  67. Kadereit, S., Deeds, L. S., Haynesworth, S. E., et al. (2002). Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34(+)/CD38(−) early progenitors cultured over human MSCs as a feeder layer. Stem Cells, 20, 573–582.

    Article  PubMed  CAS  Google Scholar 

  68. Jang, Y. K., Jung, D. H., Jung, M. H., et al. (2006). Mesenchymal stem cells feeder layer from human umbilical cord blood for ex vivo expanded growth and proliferation of hematopoietic progenitor cells. Annals of Hematology, 85, 212–225.

    Article  PubMed  Google Scholar 

  69. Robinson, S. N., Ng, J., Niu, T., et al. (2006). Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells. Bone Marrow Transplant, 37, 359–366.

    Article  PubMed  CAS  Google Scholar 

  70. Punzel, M., Liu, D., Zhang, T., Eckstein, V., Miesala, K., & Ho, A. D. (2003). The symmetry of initial divisions of human hematopoietic progenitors is altered only by the cellular microenvironment. Experimental Hematology, 31, 339–347.

    Article  PubMed  Google Scholar 

  71. Dexter, T. M., Allen, T. D., & Lajtha, L. G. (1977). Conditions controlling the proliferation of haemopoietic stem cells in vitro. Journal of Cellular Physiology, 91, 335–344.

    Article  PubMed  CAS  Google Scholar 

  72. Yamaguchi, M., Hirayama, F., Murahashi, H., et al. (2002). Ex vivo expansion of human UC blood primitive hematopoietic progenitors and transplantable stem cells using human primary BM stromal cells and human AB serum. Cytotherapy, 4, 109–118.

    Article  PubMed  CAS  Google Scholar 

  73. Wagner, W., Saffrich, R., Wirkner, U., et al. (2005). Hematopoietic progenitor cells and cellular microenvironment: Behavioral and molecular changes upon interaction. Stem Cells, 23, 1180–1191.

    Article  PubMed  CAS  Google Scholar 

  74. Ho, A. D. (2005). Kinetics and symmetry of divisions of hematopoietic stem cells. Experimental Hematology, 33, 1–8.

    Article  PubMed  CAS  Google Scholar 

  75. Wagner, W., Wein, F., Roderburg, C., et al. (2007). Adhesion of human hematopoietic progenitor cells to mesenchymal stromal cells involves CD44. Cells Tissues Organs, (in press).

  76. Caplan, A. I., & Dennis, J. E. (2006). Mesenchymal stem cells as trophic mediators. Journal of Cellular Biochemistry, 98, 1076–1084.

    Article  PubMed  CAS  Google Scholar 

  77. Stamm, C., Liebold, A., Steinhoff, G., & Strunk, D. (2006). Stem cell therapy for ischemic heart disease: Beginning or end of the road? Cell Transplant, 15(Suppl 1), S47–S56.

    PubMed  Google Scholar 

  78. Mazhari, R., & Hare, J. M. (2007). Mechanisms of action of mesenchymal stem cells in cardiac repair: Potential influences on the cardiac stem cell niche. Nature Clinical Practice. Cardiovascular Medicine, 4(Suppl 1), S21–S26.

    Article  PubMed  Google Scholar 

  79. Grinnemo, K. H., Mansson-Broberg, A., Leblanc, K., et al. (2006). Human mesenchymal stem cells do not differentiate into cardiomyocytes in a cardiac ischemic xenomodel. Annals of Medicine, 38, 144–153.

    Article  PubMed  CAS  Google Scholar 

  80. Adewumi, O., Aflatoonian, B., Ahrlund-Richter, L., et al. (2007). Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nature Biotechnology, 25, 803–816.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors thank Patrick Horn and Anke Diehlmann for their support in MSC culture and photo documentation. This work was supported by the German Ministry of Education and Research (BMBF) within the National Genome Research Network NGFN-2 (EP-S19T01) and within the supporting program “cell based regenerative medicine” (START-MSC), the German Research Foundation DFG (HO 914/7-1), the Joachim Siebeneicher-Stiftung and the Academy of Sciences and Humanities, Heidelberg (WIN-Kolleg).

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  1. Department of Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Wolfgang Wagner & Anthony D. Ho

  2. Department of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120, Heidelberg, Germany

    Wolfgang Wagner

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Wagner, W., Ho, A.D. Mesenchymal Stem Cell Preparations—Comparing Apples and Oranges. Stem Cell Rev 3, 239–248 (2007). https://doi.org/10.1007/s12015-007-9001-1

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