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In vitro characterization and in vivo analysis of the differentiation potential of murine mesenchymal stem cells from bone marrow and compact bone

Grant number: 15/19018-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2015
Effective date (End): October 31, 2016
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Dimas Tadeu Covas
Grantee:Rafaela Rossetti
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The existence of non-hematopoietic stem cells in bone marrow was suggested in the late twentieth century, when it was observed that reticular cells from bone marrow fragments showed in vivo osteogenic potential, being able to generate ectopic ossicle after transplant. Later, the subpopulation of cells responsible for this potential was identified and subsequently denominated mesenchymal stem cells (MSCs). Since then, several studies contributed to the characterization of these cells in vitro. However, evidence about the biology of the cells in vivo has been only recently reported, suggesting a perivascular niche for MSCs. This concept disseminated rapidly, however, recent studies using in vivo lineage tracing by genetic recombination suggest that MSCs do not occupy the perivascular niche but occupy the endosteum of young animals. Moreover, in young animals these endosteal MSCs, and not the perivascular MSCs, would be the main responsible for the generation of skeletal tissue in the bone marrow. Then, it was hypothesized that, after youth, the bone marrow would be composed of two populations of MSCs that would occupy two distinct niches: a perivascular and a endosteal population. Nevertheless, both populations have not been directly compared yet in relation to clonogenicity and the differentiation potential in vivo. Thus, using MSCs from the bone marrow and from the compact bone of mice, this work aims to study the characteristics of these cells in vitro and, by clonal syngeneic transplants, to evaluate its differentiation potential in vivo. It is expected that the findings might contribute to refine the knowledge about the biology and identity of MSCs in the bone marrow and serve as subsidies for improving the selection of cell populations for clinical use, according to their differentiation potential in vivo.