Stem Cell Therapy for Articular Cartilage Repair: Review of the Entity of Cell Populations Used and the Result of the Clinical Application of Each Entity

Abstract

Background: Following successful preclinical studies, stem cell therapy is emerging as a candidate for the treatment of articular cartilage lesions. Because stem cell therapy for cartilage repair in humans is at an early phase, confusion and errors are found in the literature regarding use of the term stem cell therapy in this field. Purpose: To provide an overview of the outcomes of cartilage repair, elucidating the various cell populations used, and thus reduce confusion with regard to using the term stem cell therapy. Study Design: Systematic review. Methods: The authors systematically reviewed any studies on clinical application of mesenchymal stem cells (MSCs) in human subjects. A comprehensive search was performed in MEDLINE, EMBASE, the Cochrane Library, CINAHL, Web of Science, and Scopus for human studies that evaluated articular cartilage repair with cell populations containing MSCs. These studies were classified as using bone marrow–derived MSCs, adipose tissue–derived MSCs, peripheral blood–derived MSCs, synovium-derived MSCs, and umbilical cord blood–derived MSCs according to the entity of cell population used. Results: Forty-six clinical studies were identified to focus on cartilage repair with MSCs: 20 studies with bone marrow–derived MSCs, 21 studies with adipose tissue–derived MSCs, 3 studies with peripheral blood–derived MSCs, 1 study with synovium-derived MSCs, and 1 study with umbilical cord blood–derived MSCs. All clinical studies reported that cartilage treated with MSCs showed favorable clinical outcomes in terms of clinical scores or cartilage repair evaluated by MRI. However, most studies were limited to case reports and case series. Among these 46 clinical studies, 18 studies erroneously referred to adipose tissue–derived stromal vascular fractions as “adipose-derived MSCs,” 2 studies referred to peripheral blood–derived progenitor cells as “peripheral blood–derived MSCs,” and 1 study referred to bone marrow aspirate concentrate as “bone marrow–derived MSCs.” Conclusion: Limited evidence is available regarding clinical benefit of stem cell therapy for articular cartilage repair. Because the literature contains substantial errors in describing the therapeutic cells used, researchers need to be alert and observant of proper terms, especially regarding whether the cells used were stem cells or cell populations containing a small portion of stem cells, to prevent confusion in understanding the results of a given stem cell–based therapy.