Pondering the Potential of Hyaline Cartilage–Derived Chondroprogenitors for Tissue Regeneration: A Systematic Review

Abstract

Objective Chondroprogenitors have recently gained prominence due to promising results seen in in vitro and animal studies as a potential contender in cell-based therapy for cartilage repair. Lack of consensus regarding nomenclature, isolation techniques, and expansion protocols create substantial limitations for translational research, especially given the absence of distinct markers of identification. The objective of this systematic review was to identify and collate information pertaining to hyaline cartilage–derived chondroprogenitors, with regard to their isolation, culture, and outcome measures. Design As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a web-based search of Scopus and PubMed databases was performed from January 2000 to May 2020, which yielded 509 studies. A total of 65 studies were identified that met the standardized inclusion criteria which comprised of, but was not limited to, progenitors derived from fibronectin adhesion, migrated subpopulation from explant cultures, and single-cell sorting. Result Literature search revealed that progenitors demonstrated inherent chondrogenesis and minimal tendency for hypertrophy. Multiple sources also demonstrated significantly better outcomes that bone marrow–derived mesenchymal stem cells and comparable results to chondrocytes. With regard to progenitor subgroups, collated evidence points to better and consistent outcomes with the use of migratory progenitors when compared to fibronectin adhesion assay–derived progenitors, although a direct comparison between the two cell populations is warranted. Conclusion Since chondroprogenitors exhibit favorable properties for cartilage repair, efficient characterization of progenitors is imperative, to complete their phenotypic profile, so as to optimize their use in translational research for neocartilage formation.

Cell sources proposed for nucleus pulposus regeneration

“…180,181 As chondrocytes also exhibit favorable properties for cartilage repair, there are systematic reviews that have collated information on the culture and expansion capability of chondrocytes; highlighting that chondrogenic phenotype can be maintained using low glucose and hypoxic conditions. 182 63,176 In vivo chondrocytes demonstrated the potential for long-term survival of transplanted cells; transplanted autologous auricular chondrocytes were shown to survive for at least 6 months in a rabbit model, 178 and porcine articular cartilage remained viable at 12 months post injection into a porcine model. 184 ‡ ‡ ‡ ‡ Throughout the studies using chondrocytes for cell therapy for IVD regeneration, the cells were shown to be tolerant to the IVD environment, most probably due to its similarities to the condition of cartilage the chondrocytes are derived, and remain viable post-transplantation in small animal models.…”

Migratory chondroprogenitors retain superior intrinsic chondrogenic potential for regenerative cartilage repair as compared to human fibronectin derived chondroprogenitors

“…Though a multitude of reports using cell-based therapy has demonstrated therapeutic efficiency, the ensuing fibrocartilage tissue tends to be a poor substitute for long-term subsistence 39 . The discovery of cartilage resident progenitors, displaying superior chondrogenic potential and lower hypertrophic tendencies, has led to the evaluation of their use for tissue engineering applications 23 . However, clarification of their biological properties is warranted before their therapeutic use can be considered.…”

“…Both fibronectin adhesion assay derived 19 , 20 and migratory chondroprogenitors 8 , 21 have been likened to MSCs as delineated by the International Society for Cellular Therapy (ISCT) 2006 22 , demonstrating plastic adherence, similar surface marker expression, and trilineage differentiation potential. Extensive work on these progenitors has provided information on their growth characteristics, where fibronectin-derived cells displayed clonal growth and required additional growth factors for expansion, unlike migratory progenitors 23 . As compared to bone marrow-MSCs, independent in- vivo animal studies using these progenitors show that they are more effective in repairing chondral defects 11 , 24 .…”

Prospective Isolation and Characterization of Chondroprogenitors from Human Chondrocytes Based on CD166/CD34/CD146 Surface Markers

“…[8][9][10] To optimize the use of chondroprogenitors, numerous techniques for isolation based on migratory ability, selective adhesion to fibronectin, and specific cell surface marker profile have been studied. 11 The fibronectin differential adhesion assay, a commonly employed technique for isolation of chondroprogenitors, has repeatedly yielded cells demonstrating superiority for chondrogenesis. Some characteristics of the chondroprogenitors include differential adhesion to fibronectin, 2,12 differential expression of integrins and Notch proteins, 13,14 and high replicative potential, with the ability to form large number of colonies even with low seeding density.…”