Dual delivery of encapsulated BM‐MSCs and BMP‐2 improves osteogenic differentiation and new bone formation

Abstract

Stem cell-based therapies provide a promising approach for bone repair. In the present work, we developed a novel 3D vehicle system for dual-delivery of encapsulated bone marrow mesenchymal stem cells (BM-MSCs) and bone morphogenetic protein-2 (BMP-2) for treatment of large bone defects. The vehicle system consists of sodium alginate microcapsules and polylactic acid (PLLA) microspheres. BM-MSCs are encapsulated in the microcapsules, and BMP-2 proteins are encapsulated in the PLLA microspheres. This vehicle system acted as a multicore structure for sustained release of BMP-2, which enabled pulsed dosing induction of osteogenic differentiation of the co-embedded BM-MSCs. in vitro experiments showed that the loaded BMP-2 was constitutively released up to 30 days. Bioactivity of the incorporated BMP-2 in the microspheres was preserved and osteogenic differentiation of the BM-MSCs in the microcapsules was improved. In vivo, osteogenesis studies demonstrated that satisfactory degree of repair of a rat calvarial defect was achieved with the delivery of either encapsulated BM-MSCs alone or encapsulated BMP-2 alone.Transplantation of encapsulated both BM-MSCs and BMP-2 exhibited the greatest repair potential following 4-or 8-weeks treatment. In conclusion, microencapsulation of BM-MSCs and BMP-2 promoted the maturity of newly generated bone and improved new bone formation. Transplantation of BM-MSCs and BMP-2 in our novel 3-D vehicle system is a promising strategy for regenerative therapies of large bone defects.

The therapeutic potential of mesenchymal stem cells in treating osteoporosis

“…BM-MSCs have various biological advantages in terms of tissue repair, and their high osteogenic differentiation, the means of which are widely applied to the repair of bone and cartilage injuries [ 56 ]. Previous studies have mainly focused on clarifying the positive role of BM-MSCs in promoting osteogenesis [ 57 , 58 ]. The efficacy of BM-MSCs in the treatment of OP has been demonstrated in quite a few preclinical animal models, as indicated in the previously reported two studies where both the haemopoietic system and the bone marrow microenvironment were normalized after the direct infusion of allogeneic bone marrow cells into the bone marrow cavity of irradiated SAMP6 mice, and the levels of IL-6, RANKL and IL-11, involved in regulating bone reconstruction, returned to normal, similar to those of B6 mice, thereby ameliorating the imbalance between bone formation and resorption [ 59 , 60 ].…”

Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

“…Several interesting attempts have been made in recent years to develop approaches that allow a sustained and more physiological BMP-2 release. Kong and collaborators designed a system for delivering encapsulated allogenic BM-MSCs and BMP-2 into the fracture site [ 172 ]. BMP-2 was loaded into PLA microspheres, while BM-MSCs were encapsulated, together with BMP-2 containing microspheres, into sodium alginate microcapsules.…”

FOXO3 is targeted by miR-223-3p and promotes osteogenic differentiation of bone marrow mesenchymal stem cells by enhancing autophagy

“…Multifunctional MSCs have the abilities of self-renewal and differentiation into osteoblasts, chondrocytes, or adipocytes [1]. Bone marrow MSCs (BM-MSCs), in particular, play a pivotal role during bone formation, and have attracted great attention for their ability to induce osteogenic differentiation and their secretion of growth factors and cytokines [2]. In clinical practice, osteogenic differentiation of BM-MSCs has been widely applied to the treatments such as large bone fracture and bone-related tissue engineering [3].…”