Regenerative medicine in orthopedics using cells, scaffold, and microRNA

Abstract

Cells, scaffold, and growth factors are crucially important in regenerative medicine and tissue engineering. Progress in science and technology has enabled development of these three factors, with basic research being applied clinically. In the past decade, we have investigated tissue regeneration in animal models of musculoskeletal disorders by using cells, scaffold, and delivery systems which has been relatively easy to apply and develop in clinical settings. Moreover, microRNA (miRNA), which are important in biological processes and in the pathogenesis of human diseases, have been used in research on regenerative medicine. For the cell source, we focused on mesenchymal stem cells (MSC) and CD34(+) and CD133(+) cells as endothelial progenitor cells for regeneration of musculoskeletal organs. These cells are accessible and safe. For less invasive and more effective therapy, we developed a novel cell-delivery system using magnetic force to accumulate cells at a desired site. Furthermore, administration of synthetic miRNA could enhance tissue regeneration. In our studies, use of these cells combined with a cell-delivery system, miRNA, scaffold, and cytokines has led to effective regeneration of musculoskeletal tissues including cartilage, bone, ligaments, muscle, peripheral nerves, and spinal cord. The current and future objective is more effective and less invasive cell-based therapy with spatial control of transplanted cells by use of an external magnetic force. Analysis of efficiency, safety, and the mechanism of tissue regeneration by cells, scaffold, and miRNA will lead to more promising regenerative medicine, involving the development of a new generation of therapy. This review will focus on our regenerative medicine research, which focuses on clinical application of cells, scaffold, and miRNA.

Fig. 1

External magnetic device

Fig. 2

a cartilage defect of mini pig, and intra-articular injection of magnetically labeled MSC into the knee joint under magnetic force. b Safranin O staining of articular cartilage at 12 weeks

Fig. 3

Future direction of regeneration medicine using cell, scaffold, growth factors, and microRNA