Bone Marrow Mesenchymal Stem Cells Derived from Juvenile Macaques Reversed the Serum Protein Expression Profile in Aged Macaques.

Abstract

Objective: The aim of the study was to reveal the changes in serum protein composition and content in macaques during the process of ageing, and explore the effect of bone marrow mesenchymal stem cell (BMMSC) on the serum protein expression profile in elderly macaques.

Methods: Naturally ageing macaques were assessed according to age. BMMSCs were intravenously infused into aged macaques. In addition, peripheral blood was collected to obtain serum for dataindependent acquisition (DIA) protein sequencing to identify aging-related indicators. One hundred eighty days after macaques received BMMSC treatment, haemoxylin and eosin (HE) staining was performed to observe the morphology and structure of aortic arches.

Results: Compared to infant and young control macaques, aged macaques showed erythema on the face, dry skin, reduced amounts of hair on the head and back, and paleness. Cultured BMMSCs from the 4th passage (P4 BMMSCs) were grown in accordance with standards used to culture mesenchymal stem cells. After BMMSC treatment, the assessed aortic arches showed no calcium salt deposition or cell necrosis, and the characteristics of the serum protein expression profile tended to be similar to that of the infant and young groups, with the expression of 41 proteins upregulated with age and that of 30 proteins downregulated with age but upregulated after BMMSC treatment. Moreover, we identified 44 significantly differentially expressed proteins between the aged model and treatment groups; 11 of the upregulated proteins were related to vascular ageing, neuronal ageing and haematopoiesis, and 33 of the downregulated proteins were associated with neuronal ageing, cardiovascular disease, and tumours. Interestingly, S100 expression in serum was significantly decreased, COMP expression was significantly increased, NKAP expression reappeared, and LCN2, CSF1R, CORO1C, CSTB and RSU-1 expression disappeared after BMMSC treatment.

Conclusion: BMMSCs can reverse ageing-related serum protein expression.