Osteogenically differentiated mesenchymal stem cells induced by hydrolyzed fish collagen maintain their immunomodulatory effects

Abstract

AimsThe reciprocity between stem cells and biomaterials is an essential topic in bone tissue engineering. Bone marrow mesenchymal stromal cells (BMSCs) have attracted considerable attention in regenerative medicine owing to their ability to self-renew and differentiate into osteoblasts, and more importantly, their immunomodulatory effects on the immune response. Ideal biomaterials should be osteo-inductive, environmentally sustainable, and economical. Our previous study showed that hydrolyzed fish collagen (HFC) can meet each of the above requirements. However, it is still unclear whether BMSCs maintain their immunomodulatory properties after osteogenic differentiation induced by HFC. Main methodsNon-commercial sources of BMSCs were isolated from Sprague-Dawley (SD) rats. Osteogenically differentiated BMSCs induced by HFC and undifferentiated BMSCs were co-cultured with PBMC or NR 8383 macrophages, respectively. Cell proliferation of PBMC was examined using a BrdU uptake assay. In addition, the IL-6, TGF-β1, IL-10, PGE2, and nitric oxide levels were determined. The expressions of TSG-6 (TNF-stimulated gene 6) and IDO (indoleamine 2, 3-dioxygenase) genes were analyzed using qRT-PCR. Key findingsThe results revealed that HFC-induced BMSCs suppressed the proliferation of PBMC. The expression levels of anti-inflammatory mediators including IL-6, TGF-β1, and PGE2 significantly increased after 48 h of co-culture. Moreover, the nitric oxide production increased during osteogenesis induced by HFC, whereas the level of TSG-6 and IDO remained unchanged after osteogenic differentiation. HFC-BMSCs inhibited the inflammatory mediator production (IL-1β, TNF-α) in LPS-stimulated macrophages. SignificanceTaken together, these findings suggest that the immunomodulation ability is still retained in osteogenically differentiated BMSCs induced by HFC.