Certain biological properties of multipotent mesenchymal stromal cells from bone marrow and adipose tissue of FVB mice

Home/2017, Vol. 5, No. 2/Certain biological properties of multipotent mesenchymal stromal cells from bone marrow and adipose tissue of FVB mice

Certain biological properties of multipotent mesenchymal stromal cells from bone marrow and adipose tissue of FVB/N mice

Rodnichenko A. E.
State Institute of Genetic and Regenerative Medicine National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine

Multipotent mesenchymal stromal cells (MMSCs) are used for cell therapy of lesions of various genesis. The most widely used MMSCs are from two tissue sources: bone marrow and adipose tissue.
The purpose of the work was to conduct a comparative assessment of the biological properties of murine bone marrow-derived and adipose tissue-derived MMSCs.
Methods. The culture of MMSCs was obtained from the bone marrow and adipose tissue of 6 months-old male FVB/N mice according to standard protocols. We performed phenotyping, directed osteogenic and adipogenic differentiation, analysis of immunomodulatory properties in vitro of obtained cell cultures.
Results. The cultured MMSCs from bone marrow and adipose tissue express the typical stromal markers (CD44, CD73, CD90 and Sca-1). A distinctive feature of bone marrow cells cultures of the 2nd passage was the high level of the hematopoietic markers CD45 and CD117 expression. MMSCs from both tissue sources are capable of differentiation in the osteogenic and adipogenic directions. At the same time, there were differences in the differentiation in the osteogenic direction – adipose tissue-derived MMSCs had a lower osteogenic potential. MMSCs exhibit inhibitory effect on mitogen-induced proliferation of splenocytes in vitro, expression of which does not depend of tissue origin of the MMSCs with significant inhibition of mitogen-induced proliferation of splenocytes at addition of high doses of MMSCs.
Conclusions. MMSCs of bone marrow and adipose tissue express a similar level of surface markers that are characteristic of cells with multipotent properties. They are capable to differentiating in osteo- and adipogenic direction with differences in the degree of mineralization of the extracellular matrix and exhibit immunomodulatory effects in vitro, regardless of tissue origin.

Keywords: multipotent mesenchymal stromal cells; bone marrow; adipose tissue; directed cell differentiation; immunomodulation



1. Friedenstein AJ, Chailakhian RK, Lalykina KS. The development of fibroblast colonies in monolaier cultures of guinea pig bone marrow and spleen colonies. Cell Tissue Kinet. 1970; 3: 393-403.
2. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001; 7: 211-226.
3. Fernandes KJ, Fernandes IA, McKenzie, et al. A dermal niche for multipotent adult skin-derived precursor cells. Nat Cell Biol. 2004; 6: 1082-1093.
4. Miao Z, Jin J, Chen L, et al. Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells. Cell Biol Int. 2006; 30: 681-687.
5. Kruglov PV, Lokhmatova EA, Klimovich VB, et al. Mezenkhimnye stvolovye kletki i immunopatologicheskie sostoyaniya organizma [Mesenchymal stem cells and immunopathological states of the body]. Kletochnaya transplantol i tkanevaya inzheneriya – Cellular Transplantation and Tissue Engineering. 2006; 3: 36-41. [In Russian]
6. Hass R, Kasper C, Bohm S, et al. Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cells Comunication and Signalling. 2011; 9: 1-14.
7. Harvanová D, Tóthová T, Sarišský M, et al. Isolation and characterization of synovial mesenchymal stem cells. Folia Biol (Praha). 2011; 57(3): 119-124.
8. Ferretti C, Mattioli-Belmonte M. Periosteum derived stem cells for regenerative medicine proposals: Boosting current knowledge. World J Stem Cells. 2014; 6(3): 266-277.
PMid:25126377 PMCid:PMC4131269
9. Usas A, Huard J. Muscle-derived stem cells for tissue engineering and regenerative therapy. Biomaterials. 2007; 28(36): 5401-5406.
PMid:17915311 PMCid:PMC2095130
10. Park JR, Kim E, Janf J, et al. Isolation of human dermis derived mesenchymal stem cells using explants culture method: expansion and phenotypical characterization. Cell Tissue Bank. 2015; 16(2): 209-218.
11. Kuroda Y. Kitada M, Wakao S, et al. Bone marrow mesenchymal cells: how do they contribute to tissue repair and they really stem cells? Arch Immunol Ther Exp. 2011; 59: 369-378.
12. Orlic D, Kajstura J, Cimenti S. Bone marrow cells regenerate infarcted myocardium. Nature. 2011; 410: 701-705.
13. Sekiya I, Larson BL, Vuoristo JT, et al. Adipogenic differentiation of human adult stem cells from bone marrow stroma (MSCs). J Bone Miner Res. 2004; 2: 256-264.
14. Bommie F, Sung-No J. The Immunomodulatory Effects of Mesenchymal Stem Cells in Prevention or Treatment of Excessive Scars. Stem Cells International. 2016; Available: https:// dx.doi.org/10.1155/2016/6937976
15. Tyndall A, Uccelli A. Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks. Bone marrow transplantation. 2009; 43(11): 821-828.
16. Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006; 107(7): 3670-372.
17. Jiang XX, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005; 105(10): 4120-4126.
18. Friedenstein AJ, Petrakova KV, Kurolesova AI, et al. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 1968; 6: 230-247.
19. Rodbell M. Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem. 1964; 239: 375-380.
20. Cawthorn WP, Scheller EL, MacDougland OA. Adipose tissue stem cells meet preadipocyte commitment: going back to the future. J Lipid Res. 2012; 53: 227-246.
PMid:22140268 PMCid:PMC3269153
21. Tsuji W, Rubin JP, Marra KG. Adipose-derived stem cells: implications in tissue regeneration. World J Stem Cells. 2014; 6: 312-321.
PMid:25126381 PMCid:PMC4131273
22. Meirelles LDS, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. Journal of Cell Science. 2006; 119(11): 2204-2213.
23. Kern S, Eichler H, Stoeve J, et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006; 24(5): 1294-1301.
24. Izadpanah R, Trygg C, Patel B, et al. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem. 2006; 99: 1285-1297.
PMid:16795045 PMCid:PMC4048742
25. Mitchell JB, McIntosh K, Zvonic S, et al. Immunophenotype of human adipose-derived cells: temporal changes in stromalassociated and stem cell-associated markers. Stem Cells. 2006; 24: 376-385.
26. Jeon BG, Kumar BM, Kang EJ, et al. Characterization and comparison of telomere length, telomerase and reverse transcriptase activity and gene expression in human mesenchymal stem cells and cancer cells of various origins. Cell Tissue Res. 2011; 345: 149-161.
27. Sachs PC, Francis MP, Zhao M, et al. Defining essential stem cell characteristics in adipose-derived stromal cells extracted from distinct anatomical sites. Cell Tissue Res. 2012; 349: 505-515.
PMid:22628159 PMCid:PMC3746068
28. Lindroos B, Suuronen R, Miettinen S. The potential of adipose stem cells in regenerative medicine. Stem Cell Rev. 2011; 7: 269-291.
29. Bear PC, Kuci S, Krause M, et al. Comprehensive phenotype characterization of human adipose-derived stromal/stem cells and their subsets by a high throughput technology. Stem Cells Dev. 2013; 22: 330-339.
30. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284: 143-147.
31. Furno D, Mannino G, Cardile V, et al. Potential Therapeutic Applications of Adipose-Derived Mesenchymal Stem Cells. Stem Cells and Development. 2016; 25(21): 1615-1628. Available: https://doi.org/10.1089/scd.2016.0135
32. Uzbas E, May ID, Parisi AM, et al. Molecular physiognomies and applications of adipose-derived stem cells. Stem Cell Rev Rep. 2015; 2: 298-308.
33. Baptista LS, Silva KR, Borojevic R. Obesity and weight loss could alter the properties of adipose stem cells? World J Stem Cells. 2015; 7(1): 165-173.
PMid:25621116 PMCid:PMC4300927
35. Prockop DJ, Phinney DG, Bunnell BA. Mesenchymal stem cells: methods and protocols. Totowa, NJ: Humana Press, 2008. 192 p.
36. Dominici M, Le Blanc K, Mueller I. Minimal criteria for defining multipotent mesenchymal stromal cells. The International society for cellular therapy position statement. Cytotherapy. 2006; 8(4): 315-317.
37. Li J, Mareddy S, Tan DM, et al. A minimal common osteochondrocytic differentiation medium for the osteogenic and chondrogenic differentiation of bone marrow stromal cells in the construction of osteochondral graft. Tissue engineering Part A. 2009; 15(9): 2481-2490.
38. Gregory CA, Gunn WG, Peister A, et al. An alizarin red-based assay of mineralization by adherent cells in culture: comparison with cetylpyridinium chloride extraction. Analytical biochemistry. 2004; 329: 77-84.
39. Fernando AA, Dominique B. Isolation, culture, and differentiation potential of mouse marrow stromal cells. Curr Prot Stem Cell Biol. 2008; doi: 10.1002/9780470151808.sc02b03s7
40. Mosman T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1): 55-63.
41. Lakin GF. Biometrics. Higher School, Moscow, 1990. 352 p.
42. Pino AM, Rosen JC, Pablo RJ. In osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis. Biol Res. 2012; 45: 279-287.
43. Hong L, Colpan A, Peptan IA. Modulations of 17-beta estradiol on osteogenic and adipogenic differentiations of human mesenchymal stem cells. Tissue Eng. 2006; 12(10): 2747-2753.
44. Di NM, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002; 99(10): 3838-3843.
45. Le Blanc K, Tammik L, Sundberg D, et al. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol. 2003; 57(1):11-20.
46. Chamberlain G, Fox J, Ashton B, et al. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007; 25(11): 2739-2749.

Rodnichenko AE. Certain biological properties of multipotent mesenchymal stromal cells from bone marrow and adipose tissue of FVB/N mice. Cell and Organ Transplantology. 2017; 5(2):in press. doi:10.22494/cot.v5i2.77


Creative Commons License
Is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.