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.

Tissue engineering and microRNAs: future perspectives in regenerative medicine

“…Atelocollagen itself has been proposed as a system for controlled siRNA delivery. Indeed, atelocollagen-mediated delivery is effective for gene silencing in vivo, because when it is complexed with siRNAs or miRNAs, it is resistant to nucleases and can be efficiently transduced into cells [118,119]. Hydrogels have been extensively used in TE as attractive tools for local release of growth factors [120,121], drug delivery [122], and as 3D biodegradable matrices for controlled stem cell engraftment and soft tissue regeneration [123][124][125][126].…”

“…For instance, Atelocollagen Ò (Koken, Tokyo, Japan), a type I collagen gel used since 1986 in skin disorders and cosmetic surgery, has been recently proposed in a combined approach exploiting cells, scaffolds, and miRNAs for the regeneration of multiple tissues in orthopedics [118]. Atelocollagen itself has been proposed as a system for controlled siRNA delivery.…”

Magnetic cell delivery for the regeneration of musculoskeletal and neural tissues

“…Magnetic cell labeling has widely been used for the isolation of specific cell populations or in vivo cell tracking using magnetic resonance imaging (MRI) [1] , [2] . Recently, a delivery system of magnetically labeled cells, termed magnetic targeting, was developed for minimally invasive and effective cell transplantation [3] , [4] . In this system, magnetically labeled cells were locally injected into the body and controlled using an external magnetic field.…”

Effect of BMPs and Wnt3a co-expression on the osteogenetic capacity of osteoblasts

“…Bone regeneration is an important step in treating bone defects, fractured nonunion and osteoporosis. Previously, stem cells, including bone marrow-derived mesenchymal stem cells (MSCs) and others, have been used to solve the problem of obtaining seed cells for artificial bone tissue engineering (1,2). An effective way to promote the osteogenic differentiation of seed cells was to use gene therapy techniques to transfect osteoinductive regulatory factors into the seed cells, and to effectively express the regulatory factors in the seed cells, thus contributing to the osteogenic differentiation of seed cells (3,4).…”