Polymer‐encapsulated engineered adult mesenchymal stem cells secrete exogenously regulated rhBMP‐2, and induce osteogenic and angiogenic tissue formation

Abstract We have previously shown that genetically engineered adult mesenchymal stem cells (AMSCs) expressing recombinant human bone morphogenetic protein –2 (rhBMP‐2), under tet‐regulation, can induce bone formation and regeneration. We showed that these cells induce bone formation via paracrine and autocrine effect of the secreted rhBMP‐2 protein. To distinguish between these two effects, and to develop a platform for continuous delivery of rhBMP‐2 by engineered cells protected from the immune system, we have used hydrogel polymer (alginate) in order to encapsulate the AMSCs. Mixing of the cells with potassium alginate, followed by sedimentation in Ca 2+ solution, results in polymerization of the alginate around the cells, forming microcapsules composed of a membrane allowing diffusion of small molecule and proteins. Encapsulated engineered AMSCs were able to survive inside the capsules in vitro and in vivo and secrete rhBMP‐2 under tet‐regulation. Transplantation of capsules both subcutaneously and into bone defect elicited physiological response manifested in osteogenic tissue composed of bone trabeculae and cartilage. Inside the capsules, engineered AMSCs differentiated to chondrocytes (autocrine effect), but not to osteoblasts. Newly formed bone has developed around the polymeric external layer without any observed intermediate layer of tissue. There was no evidence of immune response in the transplants area. We therefore conclude that engineered AMSCs can be efficiently encapsulated within polymeric alginate microcapsules, maintain viability, differentiate by autocrine effect, secrete rhBMP‐2 under exogenous regulation, and induce bone formation by paracrine effect, with no adverse or immune response to the transplanted capsules. Copyright © 2003 John Wiley & Sons, Ltd.