Fuzheng Buxue Dietary Therapy-Preconditioned MSC-Derived Extracellular Vesicles Promote Hematopoietic Recovery in...

BackgroundChemotherapy-induced myelosuppression (CIM) is a common dose-limiting toxicity that compromises chemotherapy continuity and patient outcomes. In the bone marrow microenvironment, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) act as key paracrine mediators, regulating the function of CD34+ hematopoietic stem and progenitor cells (HSPCs). Based on the traditional concept of medicine-food homology, our team has developed Fuzheng Buxue dietary therapy (FBDT) and previously demonstrated its clinical efficacy in alleviating CIM. This study investigates whether FBDT alleviates CIM by modulating MSC-EV function.MethodsIn vitro, the optimal conditions for 5-fluorouracil (5-FU)-induced injury and FBDT intervention were first determined. CD34+ HSPCs were co-cultured with FBDT-preconditioned MSCs (FBDT-MSCs), and the expression of surface markers CD117 and CD150 was evaluated. Subsequently, EVs were isolated from FBDT-MSCs and co-cultured with CD34+ HSPCs. HSPC viability and CD117/CD150 expression were assessed. In vivo, a 5-FU-induced CIM rat model received tail vein injections of EVs from FBDT-MSCs (FBDT-EVs). Body weight, peripheral blood parameters, and serum CD117 and SCF levels were measured. Histopathology and organ indices of spleen, thymus, and bone marrow were analyzed. Key hematopoietic regulators (CD117, SCF, CD90) in bone marrow were detected by Western blot. Finally, serum creatinine levels in rats were measured.ResultsCo-culture with FBDT-MSCs increased HSPC numbers but did not significantly alter the distribution of CD117/CD150-defined HSPC subpopulations. FBDT-EVs enhanced the viability of CD34+ HSPCs in the co-culture system and increased the proportion of CD117+CD150+ HSPCs. Furthermore, FBDT-EVs promoted the recovery of hematopoietic function in CIM rats, with the reversal of body weight loss and restoration of key blood cell parameters. FBDT-EVs reduced CD117 protein levels in both bone marrow tissue and serum, while upregulating the expression of SCF and CD90. Serum creatinine levels were not significantly altered, suggesting no apparent renal toxicity under the present experimental conditions.ConclusionThe study identifies MSC-EVs as a potential mediator of the hematopoietic effects of FBDT and suggests that FBDT may enhance the hematopoietic reparative properties of MSC-EVs. These findings suggest that MSC-EVs may mediate, at least in part, the hematopoietic effects of FBDT and that FBDT preconditioning enhances the hematopoietic reparative potential of MSC-EVs in CIM.