Ageing is often accompanied by an increase in bone marrow fat together with reduced bone volume and diseases of the bone such as osteoporosis. As mesenchymal stem cells (MSCs) are capable of forming bone, cartilage and fat tissue, studying these cells is of great importance to understand the underlying mechanisms behind age‐related bone diseases. However, inter‐donor variation has been found when handling MSCs. Therefore, the aim of this study was to investigate the effects of donor age and sex by comparing in vitro characteristics of human bone marrow‐derived MSCs (hBMSCs) from a large donor cohort (n = 175). For this, hBMSCs were analysed for CFU‐F capacity, proliferation, differentiation capacity and surface antigen expression under standardized culture conditions. The results demonstrated a significantly reduced CFU‐F number for hBMSCs of female compared to male donors. Furthermore, there was a significant decrease in the proliferation rate, adipogenic differentiation potential and cell surface expression of SSEA‐4, CD146 and CD274 of hBMSCs with an increase in donor age. Interestingly, all these findings were exclusive to hBMSCs from female donors. Further research should focus on postmenopausal‐related effects on hBMSCs, as the results imply a functional loss and immunophenotypic change of hBMSCs particularly in aged women.

Bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for cell-based therapies. Growing evidence has indicated that overweight/obesity can change the bone marrow microenvironment, which affects some properties of BMSCs. As the overweight/obese population rapidly increases, they will inevitably become a potential source of BMSCs for clinical application, especially when receiving autologous BMSC transplantation. Given this situation, the quality control of these cells has become particularly important. Therefore, it is urgent to characterize BMSCs isolated from overweight/obese bone marrow environments. In this review, we summarize the evidence of the effects of overweight/obesity on the biological properties of BMSCs derived from humans and animals, including proliferation, clonogenicity, surface antigen expression, senescence, apoptosis, and trilineage differentiation, as well as the underlying mechanisms. Overall, the conclusions of existing studies are not consistent. Most studies demonstrate that overweight/obesity can influence one or more characteristics of BMSCs, while the involved mechanisms are still unclear. Moreover, insufficient evidence proves that weight loss or other interventions can rescue these qualities to baseline status. Thus, further research should address these issues and prioritize developing methods to improve functions of overweight- or obesity-derived BMSCs.

Bone marrow–derived mesenchymal stromal cells (BMSCs) are attractive candidates in tissue engineering and regenerative medicine. Growing evidence has suggested that a high body mass index (BMI) can affect the properties of BMSCs, resulting in a reduced quality of the cells. However, the results are not consistent. Therefore, this study aimed to investigate the influences of high BMI on human BMSCs (hBMSCs). To avoid gender bias, BMSCs from females and males were studied independently. Finally, hBMSCs from 89 females and 152 males were separately divided into the normal BMI group (18.5 kg/m² ≤ BMI < 25 kg/m²) and the high BMI group (BMI > 25 kg/m²). The cells were analyzed for the colony-forming potential; proliferation capacity; in vitro adipogenic, osteogenic, and chondrogenic differentiation potentials; and the expression of 32 common surface antigens. The results showed that high BMI did not change the number of colonies at passage 1 in females and males. In contrast, significantly reduced colony numbers at passage 4 (P4) were found in both female and male donors with high BMI. The doubling time of hBMSCs was comparable between the normal and the high BMI groups of females and males. Furthermore, the results of trilineage differentiation did not differ between the different BMI groups of males. In females, the high and the normal BMI groups also showed similar adipogenic and chondrogenic differentiation, while osteogenic differentiation was significantly enhanced in the high-BMI group. Regarding the expression of surface antigens, the expressions of CD200 and SSEA4 on hBMSCs were reduced in the high-BMI group of females and males, respectively. In conclusion, high BMI suppressed the clonogenicity of female and male hBMSCs at P4, improved the in vitro osteogenesis of female hBMSCs, and decreased the expressions of CD200 on hBMSCs in females and SSEA4 in males.

Due to their immunomodulatory and regenerative capacity, human bone marrow-derived mesenchymal stem cells (hBMSCs) are promising in the treatment of patients suffering from polytrauma. However, few studies look at the effects of sera from polytraumatized patients on hBMSCs. The aim of this study was to explore changes in hBMSC properties in response to serum from polytrauma patients taken at different time points after the trauma incident. For this, sera from 84 patients with polytrauma (collected between 2010 and 2020 in our department) were used. In order to test the differential influence on hBMSC, sera from the 1^st (D1), 5^th (D5), and 10^th day (D10) after polytrauma were pooled, respectively. As a control, sera from three healthy donors (HS), matched with respect to age and gender to the polytrauma group, were collected. Furthermore, hBMSCs from four healthy donors were used in the experiments. The pooled sera of HS, D1, D5, and D10 were analyzed by multicytokine array for pro-/anti-inflammatory cytokines. Furthermore, the influence of the different sera on hBMSCs with respect to cell proliferation, colony forming unit-fibroblast (CFU-F) assay, cell viability, cytotoxicity, cell migration, and osteogenic and chondrogenic differentiation was analyzed. The results showed that D5 serum significantly reduced hBMSC cell proliferation capacity compared with HS and increased the proportion of dead cells compared with D1. However, the frequency of CFU-F was not reduced in polytrauma groups compared with HS, as well as the other parameters. The serological effect of polytrauma on hBMSCs was related to the time after trauma. It is disadvantageous to use BMSCs in polytraumatized patients at least until the fifth day after polytrauma as obvious cytological changes could be found at that time point. However, it is promising to use hBMSCs to treat polytrauma after five days, combined with the concept of Damage Control Orthopedics (DCO).

For research and clinical use of stem cells, a suitable animal model is necessary. Hence, the aim of this study was to compare human-bone-marrow-derived mesenchymal stem cells (hBMSCs) with those from sheep (oBMSCs) and pigs (pBMSCs). The cells from these three species were examined for their self-renewal potential; proliferation potential; adhesion and migration capacity; adipogenic, osteogenic and chondrogenic differentiation potential; and cell morphology. There was no significant difference between hBMSCs and pBMSCs in terms of self-renewal potential or growth potential. The oBMSCs exhibited a significantly higher doubling time than hBMSCs from passage 7. The migration assay showed significant differences between hBMSCs and pBMSCs and oBMSCs—up to 30 min, hBMSCs were faster than both types and after 60 min faster than pBMSCs. In the adhesion assay, hBMSCs were significantly better than oBMSCs and pBMSCs. When differentiating in the direction of osteogenesis, oBMSCs and pBMSCs have shown a clearer osteogenic potential. In all three species, adipogenesis could only be evaluated qualitatively. The chondrogenic differentiation was successful in hBMSCs and pBMSCs in contrast to oBMSCs. It is also important to note that the cell size of pBMSCs was significantly smaller compared to hBMSCs. Finally, it can be concluded that further comparative studies are needed to draw a clear comparison between hBMSCs and pBMSCs/oBMSCs.