Enhancement of in vivo bone regeneration efficacy of osteogenically undifferentiated human cord blood mesenchymal stem cells

Abstract

We hypothesized that bone morphogenetic protein-2 (BMP-2) would significantly enhance in vivo bone formation efficacy of osteogenically undifferentiated human cord blood mesenchymal stem cells (hCBMSCs). To test this hypothesis, poly(lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) scaffolds (group 1), BMP-2-loaded PLGA/HA scaffolds (group 2), undifferentiated hCBMSCs seeded on PLGA/HA scaffolds (group 3), undifferentiated hCBMSCs seeded on BMP-2-loaded PLGA/HA scaffolds (group 4), and osteogenically differentiated hCBMSCs seeded on PLGA/HA scaffolds (group 5) were implanted into dorsal, subcutaneous spaces of athymic mice for 8 weeks. Histological analysis showed that group 4 exhibited the largest bone formation area. RT-PCR analysis showed that human mRNA expression of osteoblastic markers such as ALP and osteocalcin in group 4 was higher than that of the other groups. Mouse osteoblastic markers of the host cells in the implants were also expressed more in group 4 than in the other groups. This study demonstrated that hCBMSCs that were not differentiated osteogenically in vitro prior to transplantation regenerate bone negligibly in vivo and that transplantation of osteogenically undifferentiated hCBMSCs with BMP-2 delivery results in much more extensive bone formation in vivo than that of undifferentiated or osteogenically differentiated hCBMSCs.