The organization of the compartment of mesenchymal stem cells is still obscure. Two types of human stromal precursor cells are known. Both of them are analyzed in in vitro system: mesenchymal multipotent stromal cells (MMSC) and fibroblast colony forming units (CFU-F). The aim of this study was to compare the main characteristics of MMSC and CFU-F derived from the bone marrow of 24 healthy donors. Growth and differentiation parameters, as well as relative expression levels of different genes were analyzed in MMSC and CFU-F. MMSC were cultivated for 5 passages. CFU-F concentration was determined for each bone marrow sample. The data obtained demonstrated the heterogeneity and hierarchical organization of both studied populations of stromal precursor cells-MMSC and CFU-F. These two types of stromal precursor cells turned to be different in most parameters studied. Altogether MMSC seemed to be more immature cells than CFU-F and took up the higher position in hierarchical tree of mesenchymal stem cells. The rate of differentiation and proliferative potential decreased with the donor’s age in both populations MMSC and CFU-F.
Caplan, A.I. (1991) Mesenchymal stem cells. Journal of orthopaedic research: Official publication of the Orthopaedic Research Society, 9, 641-650.
Friedenstein, A.J., Gorskaja, J.F. and Kulagina, N.N. (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Experimental hematology, 4, 267-274.
Prockop, D.J. (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science (New York, N.Y.), 276, 71-74. doi:10.1126/science.276.5309.71
Short, B., Brouard, N., Occhiodoro-Scott, T., Ramakrishnan, A. and Simmons, P.J. (2003) Mesenchymal stem cells. Archives of Medical Research, 34, 565-571. doi:10.1016/j.arcmed.2003.09.007
Beyer, N.N. and Da Silva Meirelles, L. (2006) Mesenchymal stem cells: Isolation, in vitro expansion and characterization. Handbook of Experimental Pharmacology, 174, 249-282. doi:10.1007/3-540-31265-X_11
Horwitz, E.M., Le Blanc, K., Dominici, M., Mueller, I., Slaper-Cortenbach, I., Marini, F.C. et al. (2005) Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy, 7, 393-395. doi:10.1080/14653240500319234
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. doi:10.1080/14653240600855905
Nifontova, I.N., Svinareva, D.A. and Drize, N.J. (2008) Stromal clonogenic precursors of hemopoietic microenvironment and their rank in the hierarchy of mesenchymal stem cells. Bulletin of Experimental Biology and Medicine, 145, 544-547. doi:10.1007/s10517-008-0137-z
Tormin, A., Brune, J.C., Olsson, E., Valcich, J., Neuman, U., Olofsson, T., et al. (2009) Characterization of bone marrow-derived mesenchymal stromal cells (MSC) based on gene expression profiling of functionally defined MSC subsets. Cytotherapy, 11, 114-128. doi:10.1080/14653240802716590
Russell, K.C., Phinney, D.G., Lacey, M.R., Barrilleaux, B.L., Meyertholen, K.E. and O’Connor, K.C. (2010) In vitro high-capacity assay to quantify the clonal heterogeneity in trilineage potential of mesenchymal stem cells reveals a complex hierarchy of lineage commitment. Stem Cells (Dayton, Ohio), 28, 788-798. doi:10.1002/stem.312
Pevsner-Fischer, M., Levin, S. and Zipori, D. (2011) The origins of mesenchymal stromal cell heterogeneity. Stem Cell Reviews, 7, 560-568. doi:10.1007/s12015-011-9229-7
Gao, J., Dennis, J.E., Muzic, R.F., Lundberg, M. and Caplan, A.I. (2001) The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells, Tissues, Organs, 169, 12-20. doi:10.1159/000047856
Castro-Malaspina, H., Gay, R.E., Resnick, G., Kapoor, N., Meyers, P., Chiarieri, D., et al. (1980) Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny. Blood, 56, 289-301.
Cuthbert, R., Boxall, S.A., Tan. H.B., Giannoudis. P.V, McGonagle, D. and Jones, E. (2012) Single-platform quality control assay to quantify multipotential stromal cells in bone marrow aspirates prior to bulk manufacture or direct therapeutic use. Cytotherapy, 14, 431-440. doi:10.3109/14653249.2011.651533
Chomczynski, P. and Sacchi, N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanatephenol-chloroform extraction. Analytical Biochemistry, 162, 156-159. doi:10.1016/0003-2697(87)90021-2
Schmittgen, T.D. and Livak, K.J. (2008) Analyzing realtime PCR data by the comparative CT method. Nature Protocols, 3, 1101-1108. doi:10.1038/nprot.2008.73
Galotto, M., Berisso, G., Delfino, L., Podesta, M., Ottaggio, L., Dallorso, S., et al. (1999) Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients. Experimental Hematology, 27, 1460-1466. doi:10.1016/S0301-472X(99)00076-4
Gothard, D., Dawson, J.I. and Oreffo, R.O.C. (2013) Assessing the potential of colony morphology for dissecting the CFU-F population from human bone marrow stromal cells. Cell and Tissue Research, 352, 237-247. doi:10.1007/s00441-013-1564-3
S. Kaneko, S. Motomura and H. Ibayashi (1982) Differentiation of human bone marrow-derived fibroblastoid colony forming cells (CFU-F) and their roles in haemopoiesis in vitro. British Journal of Haematology, 51, 217-225. doi:10.1111/j.1365-2141.1982.tb02774.x
Svinareva, D.A., Shipunova, I.N., Ol’shanskaia, I.V, Momotiuk, K.S., Drize, N.I. and Savchenko, V.G. (2010) The basic properties of mesenchymal stromal cells from the donor bone marrow: Superficial markers. Terapevticheskii Arkhiv, 82, 52-56.
Maijenburg, M.W., Kleijer, M., Vermeul, K., Mul, E., Alphen, F. Van, Schoot, C.E. Van Der, et al. (2011) The composition of the mesenchymal stromal cell compartment in human bone marrow changes during development and aging. doi:10.3324/haematol.2011.047753
Maijenburg, M.W., Kleijer, M., Vermeul, K., Mul, E.P.J., Van Alphen, F.P.J., Van der Schoot, C.E. et al. (2012) The composition of the mesenchymal stromal cell compartment in human bone marrow changes during development and aging. Haematologica, 97, 179-183. doi:10.3324/haematol.2011.047753
Gospodarowicz, D., Neufeld, G. and Schweigerer, L. (1987) Fibroblast growth factor: structural and biological properties. Journal of cellular physiology. Supplement, S5, 15-26.
Neufeld, G. and Gospodarowicz, D. (1986) Basic and acidic fibroblast growth factors interact with the same cell surface receptors. The Journal of Biological Chemistry, 261, 5631-5637.
Peters, K.G., Werner, S., Chen, G. and Williams, L.T. (1992) Two FGF receptor genes are differentially expressed in epithelial and mesenchymal tissues during limb formation and organogenesis in the mouse. Development (Cambridge, England), 114, 233-243.
Kuznetsov, S.A., Friedenstein, A.J. and Robey, P.G. (1997) Factors required for bone marrow stromal fibroblast colony formation in vitro. British Journal of Haematology, 97, 561-570. doi:10.1046/j.1365-2141.1997.902904.x
Stolzing, A., Jones, E., McGonagle, D. and Scutt, A. (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies. Mechanisms of Ageing and Development, 129, 163-173. doi:10.1016/j.mad.2007.12.002
Colter, D.C., Sekiya, I. and 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. doi:10.1073/pnas.141221698
Bigildeev, A.E., Zhironkina, O.A., Shipounova, I.N., Sats, N.V, Kotyashova, S.Y. and Drize, N.I. (2012) Clonal composition of human multipotent mesenchymal stromal cells. Experimental Hematology, 40, 847-856.e4. doi:10.1016/j.exphem.2012.06.006
Muraglia, A., Cancedda, R. and Quarto, R. (2000) Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. Journal of Cell Science, 113, 1161-1166.
Banfi, A., Muraglia, A., Dozin, B., Mastrogiacomo, M., Cancedda, R. and Quarto, R. (2000) Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: Implications for their use in cell therapy. Experimental Hematology, 28, 707-715. doi:10.1016/S0301-472X(00)00160-0
Suva, D., Garavaglia, G., Menetrey, J., Chapuis, B., Hoffmeyer, P., Bernheim, L., et al. (2004) Non-hematopoietic human bone marrow contains long-lasting, pluripotential mesenchymal stem cells. Journal of Cellular Physiology, 198, 110-118. doi:10.1002/jcp.10396
Nifontova, I., Svinareva, D., Petrova, T. and Drize, N. (2008) Sensitivity of mesenchymal stem cells and their progeny to medicines used for the treatment of hematoproliferative diseases. Acta Haematologica, 119, 98-103. doi:10.1159/000120440
Hernigou, P., Poignard, A., Beaujean, F. and Rouard, H. (2005) Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. The Journal of Bone and Joint Surgery. American Volume, 87, 1430-1437. doi:10.2106/JBJS.D.02215