Identification of a clinical signature predictive of differentiation fate of human bone marrow stromal cells

• Published in: Stem cell research & therapy Vol. 12; no. 1; p. 265
• Main Authors: Kowal, Justyna Magdalena, Möller, Sören, Ali, Dalia, Figeac, Florence, Barington, Torben, Schmal, Hagen, Kassem, Moustapha
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.05.2021; BioMed Central; BMC
• Subjects: Alfacalcidol; Bone growth; Bone marrow; Bone marrow transplantation; Bone surgery; Calcifediol; CD markers; Cell differentiation; Cell growth; Cell phenotype; Clinical trials; Donor characteristics; Flow cytometry; Fractures; Gene expression; Human bone marrow stromal stem cells; Osteoblastic and adipocytic differentiation; Osteoblastogenesis; Osteoblasts; Osteogenesis; Osteoporosis; Phosphates; Regeneration; Software; Stem cells; Stromal cells; Tissue engineering; Vitamin D; Denmark; Human bone marrow stromal stem cells; Donor characteristics; Cell phenotype; CD markers; Osteoblastic and adipocytic differentiation
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-021-02338-1

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. 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. We 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. We 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. Using 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.