Abstract
Bone marrow adipose tissue (BMAT) exhibits a multitude of biological functionalities and influences hematopoiesis. The adiposity status of the bone marrow may play a role in the decline of hematopoietic function. Mesenchymal stem cells (MSCs) constitute crucial regulators within the bone marrow microenvironment; however, their precise role in modulating BMAT and the subsequent implications for hematopoiesis remain poorly understood. We conducted in vivo studies to observe the effects of human umbilical cord mesenchymal stem cells (hucMSCs) on BMAT accumulation and restoration of hematopoietic function in mice with drug-induced hematopoietic impairment. Concurrently, in vitro co-culture experiments were used to investigate the impact of hucMSCs on preadipocytes and mature adipocytes, and the potential subsequent consequences for hematopoietic cells. Moreover, we explored the potential mechanisms underlying these interactions. Our findings reveal that hucMSCs concomitantly mitigate BMAT accumulation and facilitate the recovery of hematopoietic function in mouse models with drug-induced hematopoietic impairment. In vitro, hucMSCs potentially impede adipogenic differentiation of 3T3-L1 preadipocytes through interference with the JAK2/STAT3 signaling pathway and affect the functionality of mature adipocytes, thus mitigating the detrimental effects of adipocytes on hematopoietic stem cells (HSCs). Furthermore, we demonstrate that hucMSCs may protect hematopoietic cells from adipocyte-induced damage by protecting antioxidative mechanisms. These results suggest that hucMSCs exhibit an inhibitory effect on the excessive expansion of adipose tissue and modulate adipose tissue function, which may potentially contribute to the regulation of the bone marrow microenvironment and favorably influence hematopoietic function improvement.