Abstract
BackgroundTransplantation of human bone marrow stromal cells (hBMSCs) is a promising therapy for bone regeneration due to their ability to differentiate into bone forming osteoblastic cells. However, transplanted hBMSCs exhibit variable capacity for bone formation resulting in inconsistent clinical outcome. The aim of the study was to identify a set of donor- and cell-related characteristics that detect hBMSCs with optimal osteoblastic differentiation capacity.MethodsWe collected hBMSCs from 58 patients undergoing surgery for bone fracture. Clinical profile of the donors and in vitro characteristics of cultured hBMSCs were included in uni- and multivariable analysis to determine their predictive value for osteoblastic versus adipocytic differentiation capacity assessed by quantification of mineralized matrix and mature adipocyte formation, respectively.ResultsWe identified a signature that explained > 50% of variation in osteoblastic differentiation outcome which included the following positive predictors: donor sex (male), absence of osteoporosis diagnosis, intake of vitamin D supplements, higher fraction of CD146+, and alkaline phosphate (ALP+) cells. With the exception of vitamin D and ALP+ cells, these variables were also negative predictors of adipocytic differentiation.ConclusionsUsing a combination of clinical and cellular criteria, it is possible to predict differentiation outcome of hBMSCs. This signature may be helpful in selecting donor cells in clinical trials of bone regeneration.
Highlights
Transplantation of human bone marrow stromal cells is a promising therapy for bone regeneration due to their ability to differentiate into bone forming osteoblastic cells
Cellular heterogeneity of in vitro cultured human bone marrow stromal cells (hBMSCs) are caused by intrinsic factors related to stem cells, i.e., differences in numbers (indicated by colony-forming efficiency or CD marker expression), proliferation rate, and factors related to their differentiation capacity, i.e., the ability of the cells to differentiate into bone-forming osteoblastic cells or cells of alternative lineages such as adipocytic cells, which is considered an unwanted outcome when developing therapies for bone regeneration [18,19,20,21,22]
Using univariable and multivariable analysis, we identified a set of variables predictive for the ability of the cultured hBMSCs to differentiate into bone-forming osteoblastic cells
Summary
Transplantation of human bone marrow stromal cells (hBMSCs) is a promising therapy for bone regeneration due to their ability to differentiate into bone forming osteoblastic cells. The aim of the study was to identify a set of donor- and cell-related characteristics that detect hBMSCs with optimal osteoblastic differentiation capacity. Cellular heterogeneity of in vitro cultured hBMSCs are caused by intrinsic factors related to stem cells, i.e., differences in numbers (indicated by colony-forming efficiency or CD (cluster of differentiation) marker expression), proliferation rate, and factors related to their differentiation capacity, i.e., the ability of the cells to differentiate into bone-forming osteoblastic cells or cells of alternative lineages such as adipocytic cells, which is considered an unwanted outcome when developing therapies for bone regeneration [18,19,20,21,22]. The clinical use of hBMSCs requires determining the relative contribution of donor-related phenotype and intrinsic cellular characteristics, on osteoblast differentiation outcome, with the aim of selecting the most optimal hBMSC product for clinical applications
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