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Background: Articular chondroprogenitors are a promising contender for cartilage repair due to their inherent nature which stands primed for chondrogenesis and minimal hypertrophic preponderance. Platelet rich plasma (PRP) has been extensively used for treating cartilage defects and osteoarthritis (OA), due to its chondro-inductive properties and abundant pool of growth factors. The aim of this study was to assess the efficacy of chondroprogenitors injected with PRP versus PRP alone in the healing of experimentally created early OA and osteochondral defects (OCD) in a rabbit model., Methods: Adult New Zealand White male rabbits were used for cell and PRP isolation. Chondroprogenitors were isolated by fibronectin adhesion assay, labelled with iron oxide, characterized for surface markers, differential potential and expanded. PRP was isolated by double spin centrifugation using a TriCell kit. Study groups included (a) Monosodium iodoacetate induced early OA and (b) critical OCD. Following intervention (test arm: PRP+ chondroprogenitors and control arm: PRP), assessment was performed at 6- and 12-weeks which included histopathological examination and scoring (OARSI and Modified Wakitani score), immunohistochemistry analysis (Collagen type II and X) and synovial fluid S100A12 levels., Results and Conclusion: Comparable, evident healing was noticed in both test and control arms when the OA group samples were assessed at both time points. In the OCD group, PRP alone exhibited significantly better results than the test arm, although repair was notable in both interventions. Further evaluation of chondroprogenitors is required to assess their role as a standalone therapy and in combination with PRP to further cartilage regeneration., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cell based therapy in cartilage repair predominantly involves the use of chondrocytes and mesenchymal stromal cells (MSC). Co-culture systems, due to their probable synergistic effect on enhancement of functional chondrogenesis and reduction in terminal differentiation have also been attempted. Chondroprogenitors, derived from articular cartilage and regarded as MSCs, have recently garnered interest for consideration in cartilage regeneration to overcome limitations associated with use of conventional cell types. The aim of this study was to assess whetherco-culturing bone marrow (BM)-MSCs and chondroprogenitors at different ratios would yield superior results in terms of surface marker expression, gene expression and chondrogenic potential., Methods: Human BM-MSCs and chondroprogenitors obtained from three osteoarthritic knee joints and subjected to monolayer expansion and pellet cultures (10,000 cells/cm 2 ) as five test groups containing either monocultures or co-cultures (MSC: chondroprogenitors) at three different ratios (75:25, 50:50 and 25:75) were utilized., Results: Data analysis revealed that all groups exhibited a high expression of CD166, CD29 and CD49e. With regard to gene expression, high expression of SOX9, Aggrecan and Collagen type I; a moderate expression of Collagen type X and RUNX2; with a low expression of Collagen type II was seen. Analysis of pellet culture revealed that chondroprogenitor monoculture and chondroprogenitor dominant coculture, exhibited a subjectively larger pellet size with higher deposition of Collagen type II and glycosaminoglycan., Conclusion: In conclusion, this study is suggestive of chondroprogenitor monoculture superiority over MSCs, either in isolation or in a coculture system and proposes further analysis of chondroprogenitors for cartilage repair., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Enhanced chondrogenesis and reduction in hypertrophy are essential pre-requisites for cell-based therapy in regenerative research for cartilage loss. Chondroprogenitors, isolated by fibronectin adhesion assay (FAA), have shown promising results in various preclinical studies due to their inherent characteristics. However, the need for monolayer culture and the effect of expansion on cell phenotype render differentiation between chondroprogenitors and chondrocytes (native cartilage cells) difficult. This is further complicated due to reported de-differentiation of chondrocytes in culture. Thus, the aim of our study was to harvest cells from articular cartilage and compare their gene expression to cells demonstrating adherence and non-adherence to fibronectin., Method: Fresh-cells (FC) were isolated from human osteoarthritic knee joints(n = 3) and subjected to FAA. Cells unbound to fibronectin (20 min after plating) were termed as FAA-ve. Attached cells were further cultured for five population doublings and designated FAA+ve. RNA from all three cell groups was assessed for SOX-9, ACAN, COL2A1, COL1A1, RUNX2 and COL10A1., Results: All three groups exhibited moderate to high expression of markers of chondrogenesis and marker of chondrocyte hypertrophy. FAA+ve group exhibited significantly lower levels of hypertrophy markers: RUNX2 (vs FC and FAA-ve, P = 0.018) and COL10A1(vs FAA-ve, P = 0.005)., Conclusions: Our results demonstrated that fibronectin effectively isolated cells distinct from mature chondrocytes in terms of reduced hypertrophic tendency. This is noteworthy as cells isolated by FAA, retaining their inherent progenitor phenotype, with upregulation of chondrogenic markers may be used successfully for cartilage repair in future translational work., Competing Interests: Declaration of competing interest All author(s) declare(s) no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Cell-based therapy in cartilage repair can benefit from the use of chondroprogenitors; a cell type classified as mesenchymal stem cells, demonstrating reduced hypertrophy. Fibronectin, routinely used to isolate chondroprogenitors, classically binds to α5β1 integrins (CD49e + CD29), of which CD49e is said to be highly expressed in progenitors. The aim of our study was to assess the specificity of CD49e as a distinguishing marker for chondroprogenitors; because studies report low expression in fresh chondrocytes (FCs), but recent conflicting data has exhibited incremental expression of CD49e in cultured chondrocytes., Methods: FCs were isolated from three human osteoarthritic knee joints and CD49e- cells (sorted by flow cytometry) were cultured in adherent and non-adherent conditions and reassessed for CD49e and CD29 at multiple time points. Colony-forming efficiency (CFE) following fibronectin adhesion assay was calculated for FC, CD49e+ and CD49e- cells., Results: A statistically significant increase in CD49e and CD29 expression was seen in both adherent and non-adherent cultures of CD49e- cells (P < 0.01), as early as 24 h. All groups grew clonally and CFE was similar without any significant difference. CD49e- chondrocytes turned positive when cultured, possibly due to an inherent phenotypic drift, seen after release from cartilage and not because of plastic adherence or chondroprogenitor overgrowth, as non-adherent cultures also showed high expression., Conclusions: As the specificity of CD49e is questionable, there is a pressing need for a specific differentiating marker, to isolate a pure population of chondroprogenitors, as this cell type shows inherent chondrogenesis and reduced hypertrophy, both requisites for cartilage repair., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)