Effect of nutritional supplement on bone marrow-derived mesenchymal stem cells from aplastic anaemia

Abstract

Aplastic anaemia (AA) is characterised by pancytopenia resulting from a marked reduction in haemopoietic stem cells (HSC). The regulation of haemopoiesis depends on the interaction between HSC and various cells of the bone marrow (BM) microenvironment, including BM-derived mesenchymal stromal cells (BMSC). The purpose of this study was to analyse the biological effect of nutritional supplement (NS), a dietary supplement consisting of thirty-six compounds: amino acids, nucleotides, vitamins and micronutrients on the BMSC of AA rats. The AA rat model was established by irradiating X-ray (2·5 Gy) and intraperitoneal injections of cyclophosphamide (35 mg/kg; Sigma) and chloramphenicol (35 mg/kg; Sigma). Then AA rats were fed with NS in a dose-dependent manner (2266·95, 1511·3, 1057·91 mg/kg d) by intragastric administration. The effect of NS on the BMSC of AA rats was analysed. As compared with AA rats, NS treatment significantly improved these peripheral blood parameters and stimulated the proliferation of total femoral nucleated cells. NS treatment affected proliferative behaviour of BMSC and suppressed BMSC differentiation to adipocytes. Furthermore, NS treatment of AA rats accelerated osteogenic differentiation of BMSC and enhanced bone mineral density. Co-incubation of HSC with mesenchymal stromal cells and serum from AA rats subjected to high-dose NS markedly improved the yield of CD34+cells. Protein microarray analysis revealed that there were eleven differentially expressed proteins in the NS group compared with the AA rat group. The identified specific NS might be implicated in rehabilitation of BMSC in AA rats, suggesting their potential of nutritional support in AA treatment.

Effects of IFN-γ on the proliferation of 32D cells expressing Akt after IRF-1 gene silencing

“…The mechanism underlying IFN-γ-inhibited hematopoiesis was complex, involving several ways for the occurrence of AA. Several investigations indicated that IRF - 1 gene could activate not only the expression of IFNs but also show the activity of tumor suppressor, which can inhibit cell proliferation as an anti-cancer effect ( 11 - 13 ); also, the micro-expression of IRF-1 inhibited the cell proliferation ( 3 ). These studies showed that IRF - 1 gene plays a major role in the IFN-γ-inhibited cell proliferation.…”

Aging of mesenchymal stem cell: machinery, markers, and strategies of fighting

“…Similarly, a nutraceutical compound, methylsulfonylmethane promoted MSC differentiation, chondrogenesis, and preosteoblast formation [303]. In addition, a mixture of 36 nutrients promoted proliferation and osteogenic differentiation and inhibited adipogenesis of BMSCs from rats with aplastic anemia [304]. Indeed, piceatannol inhibited adipogenic activity in human MSC-derived adipocytes through PPARγ downregulation [305].…”