Chondrocytes, Mesenchymal Stem Cells, and Their Combination in Articular Cartilage Regenerative Medicine

Abstract

Articular cartilage (AC) is a highly organized connective tissue lining, covering the ends of bones within articulating joints. Its highly ordered structure is essential for stable motion and provides a frictionless surface easing load transfer. AC is vulnerable to lesions and, because it is aneural and avascular, it has limited self-repair potential which often leads to osteoarthritis. To date, no fully successful treatment for osteoarthritis has been reported. Thus, the development of innovative therapeutic approaches is desperately needed. Autologous chondrocyte implantation, the only cell-based surgical intervention approved in the United States for treating cartilage defects, has limitations because of de-differentiation of articular chondrocytes (AChs) upon in vitro expansion. De-differentiation can be abated if initial populations of AChs are co-cultured with mesenchymal stem cells (MSCs), which not only undergo chondrogenesis themselves but also support chondrocyte vitality. In this review we summarize studies utilizing AChs, non-AChs, and MSCs and compare associated outcomes. Moreover, a comprehensive set of recent human studies using chondrocytes to direct MSC differentiation, MSCs to support chondrocyte re-differentiation and proliferation in co-culture environments, and exploratory animal intra- and inter-species studies are systematically reviewed and discussed in an innovative manner allowing side-by-side comparisons of protocols and outcomes. Finally, a comprehensive set of recommendations are made for future studies.

Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes

“…There has been widespread interest in the use of mesenchymal stem cells in regenerative medicine and tissue engineering for repair/regeneration of hyaline cartilage defects in the body; for example regeneration of articular cartilage in joints [14,15] and cartilage defects in the head and neck area [16] for example, the nasal septum [17,18]. In comparison, there has been little research focussed on engineering hypertrophic cartilage.…”

A flow perfusion bioreactor with controlled mechanical stimulation: Application in cartilage tissue engineering and beyond

“…MSCs and AChs co-exist in vivo, and when co-cultured in vitro, both cell types interact mutually in that signaling molecules secreted by AChs induce MSC chondrogenesis and suppress their hypertrophy and the signaling molecules secreted by MSCs support ACh viability and proliferation [124]. Since our system has proven effective in inducing chondrogenesis of each cell type alone, we do not foresee any problems in utilizing the system to study co-culture environment.…”

Osteoarthritis and Mesenchymal Stem Cell Therapy: An Overview

“…In addition, as the procedure uses cell culture, these therapies are invasive and relatively expensive. [18,[33][34][35][36][37].…”