Characterization of human articular chondrocytes and chondroprogenitors derived from non-diseased and osteoarthritic knee joints to assess superiority for cell-based therapy

Vinod, Elizabeth; Kachroo, Upasana; Rebekah, Grace; Yadav, Bijesh; Ramasamy, Boopalan

doi:10.1016/j.acthis.2020.151588

Cited by 17 publications

(19 citation statements)

References 35 publications

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“…For articular cartilage progenitors, the fibronectin receptor CD49e is responsible for the increased fibronectin adhesion capacity [16]. For these cells, it was shown that the expression of CD49e did not change between passages 0 and 10 [42], but the expression of the fibronectin receptor is dynamic as it increased in culture [43]. In the meniscus, fibronectin is located in the cell membrane of fibrochondrocytes and in the territorial matrix throughout the meniscus [44].…”

Section: Discussionmentioning

confidence: 99%

Selection of Highly Proliferative and Multipotent Meniscus Progenitors through Differential Adhesion to Fibronectin: A Novel Approach in Meniscus Tissue Engineering

Korpershoek

Rikkers

Windt

et al. 2021

IJMS

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Meniscus injuries can be highly debilitating and lead to knee osteoarthritis. Progenitor cells from the meniscus could be a superior cell type for meniscus repair and tissue-engineering. The purpose of this study is to characterize meniscus progenitor cells isolated by differential adhesion to fibronectin (FN-prog). Human osteoarthritic menisci were digested, and FN-prog were selected by differential adhesion to fibronectin. Multilineage differentiation, population doubling time, colony formation, and MSC surface markers were assessed in the FN-prog and the total meniscus population (Men). Colony formation was compared between outer and inner zone meniscus digest. Chondrogenic pellet cultures were performed for redifferentiation. FN-prog demonstrated multipotency. The outer zone FN-prog formed more colonies than the inner zone FN-prog. FN-prog displayed more colony formation and a higher proliferation rate than Men. FN-prog redifferentiated in pellet culture and mostly adhered to the MSC surface marker profile, except for HLA-DR receptor expression. This is the first study that demonstrates differential adhesion to fibronectin for the isolation of a progenitor-like population from the meniscus. The high proliferation rates and ability to form meniscus extracellular matrix upon redifferentiation, together with the broad availability of osteoarthritis meniscus tissue, make FN-prog a promising cell type for clinical translation in meniscus tissue-engineering.

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Section: Discussionmentioning

confidence: 99%

Selection of Highly Proliferative and Multipotent Meniscus Progenitors through Differential Adhesion to Fibronectin: A Novel Approach in Meniscus Tissue Engineering

Korpershoek

Rikkers

Windt

et al. 2021

IJMS

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“…The second group for comparison included integrin markers: CD 49e-PE, CD29-APC, and CD49b-FITC. The third group for comparison included CD markers which are reported to be potential markers of enhanced chondrogenesis: CD166-BB515 13 , 36 , CD146-PE 17 , 37 , and Podoplanin-BV421 38 . The final group included human leucocyte antigen class I (HLA-ABC-PE), HLA class II (HLA-DR V500), and their co-stimulatory molecules, CD80-BB515 and CD86-BV421.…”

Section: Methodsmentioning

confidence: 99%

“…The potential of articular cartilage-derived chondroprogenitors has recently gained interest due to their phenotypic predisposition for chondrogenesis and reduced hypertrophic proclivity. As compared to chondrocytes and bone marrow-derived MSCs, chondroprogenitors demonstrate supremacy in terms of higher chondrogenic potential and lower expression of fibrocartilage/hypertrophy markers such as Collagen type I and RUNX2 10 – 13 . As a result, these cells open up new possibilities and strategies for cartilage regeneration and tissue engineering.…”

Section: Introductionmentioning

confidence: 99%

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

Vinod

Johnson

Kumar

et al. 2021

Sci Rep

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Cell-based therapy for articular hyaline cartilage regeneration predominantly involves the use of mesenchymal stem cells and chondrocytes. However, the regenerated repair tissue is suboptimal due to the formation of mixed hyaline and fibrocartilage, resulting in inferior long-term functional outcomes. Current preclinical research points towards the potential use of cartilage-derived chondroprogenitors as a viable option for cartilage healing. Fibronectin adhesion assay-derived chondroprogenitors (FAA-CP) and migratory chondroprogenitors (MCP) exhibit features suitable for neocartilage formation but are isolated using distinct protocols. In order to assess superiority between the two cell groups, this study was the first attempt to compare human FAA-CPs with MCPs in normoxic and hypoxic culture conditions, investigating their growth characteristics, surface marker profile and trilineage potency. Their chondrogenic potential was assessed using mRNA expression for markers of chondrogenesis and hypertrophy, glycosaminoglycan content (GAG), and histological staining. MCPs displayed lower levels of hypertrophy markers (RUNX2 and COL1A1), with normoxia-MCP exhibiting significantly higher levels of chondrogenic markers (Aggrecan and COL2A1/COL1A1 ratio), thus showing superior potential towards cartilage repair. Upon chondrogenic induction, normoxia-MCPs also showed significantly higher levels of GAG/DNA with stronger staining. Focused research using MCPs is required as they can be suitable contenders for the generation of hyaline-like repair tissue.

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“…15,16 They are also likened to mesenchymal stem cells (MSCs) since they are plastic adherent, express classical MSC markers, do not express hematopoietic markers, and display multilineage potential. [17][18][19] Furthermore, several studies assessing the effects of different culture conditions and interventions such as physioxia 20 and specific growth factors [21][22][23] on chondroprogenitors report its conduciveness for chondrogenesis. Chondroprogenitors, when compared to BM-MSCs and chondrocytes, report a higher expression of chondrogenic genes such as aggrecan, collagen type II, SOX-9, and PRG4 18,24 and a lower expression of hypertrophic markers such as RUNX2 and collagen type X, 8,10,25 indicative of superior potential for neocartilage formation.…”

Section: Introductionmentioning

confidence: 99%

“…29,30 Additionally, a recent study comparing human chondroprogenitors and chondrocytes demonstrated that progenitors with increased time in culture exhibited significantly lower CD34, higher CD166, and CD146 levels. 19 Contrarily, a few studies have also suggested that eliminating CD146 positive subsets may improve chondrogenic ability. [31][32][33] To optimize chondroprogenitor use in cell-based therapy, our study aimed to see whether a constellation of reported CD markers would help identify progenitors with the highest chondrogenic ability and least tendency for hypertrophy.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Purpose Chondrocytes, isolated from articular cartilage, are routinely utilized in cell-based therapeutics for the treatment of cartilage pathologies. However, restoration of the biological tissue faces hindrance due to the formation of primarily fibrocartilaginous repair tissue. Chondroprogenitors have been reported to display superiority in terms of their chondrogenic potential and lesser proclivity for hypertrophy. In line with our recent results, comparing chondroprogenitors and chondrocytes, we undertook isolation of progenitors from the general pool of chondrocytes, based on surface marker expression, namely, CD166, CD34, and CD146, to eliminate off-target differentiation and generate cells of stronger chondrogenic potential. This study aimed to compare chondrocytes, chondroprogenitors, CD34−CD166+CD146+ sorted chondrocytes, and CD34−CD166+CD146− sorted chondrocytes. Methods Chondrocytes obtained from 3 human osteoarthritic knee joints were subjected to sorting, to isolate CD166+ and CD34− subsets, and then were further sorted to obtain CD146+ and CD146− cells. Chondrocytes and fibronectin adhesion-derived chondroprogenitors served as controls. Assessment parameters included reverse transcriptase polymerase chain reaction for markers of chondrogenesis and hypertrophy, trilineage differentiation, and total GAG/DNA content. Results Based on gene expression analysis, CD34−CD166+CD146+ sorted chondrocytes and chondroprogenitors displayed comparability and significantly higher chondrogenesis with a lower tendency for hypertrophy when compared to chondrocytes and CD34−CD166+CD146− sorted chondrocytes. The findings were also reiterated in multilineage potential differentiation with the 146+ subset and chondroprogenitors displaying lower calcification and chondroprogenitors displaying higher total GAG/DNA content compared to chondrocytes and 146− cells. Conclusion This unique progenitor-like population based on CD34−CD166+CD146+ sorting from chondrocytes exhibits efficient potential for cartilage repair and merits further evaluation for its therapeutic application.

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Characterization of human articular chondrocytes and chondroprogenitors derived from non-diseased and osteoarthritic knee joints to assess superiority for cell-based therapy

Cited by 17 publications

References 35 publications

Selection of Highly Proliferative and Multipotent Meniscus Progenitors through Differential Adhesion to Fibronectin: A Novel Approach in Meniscus Tissue Engineering

Selection of Highly Proliferative and Multipotent Meniscus Progenitors through Differential Adhesion to Fibronectin: A Novel Approach in Meniscus Tissue Engineering

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

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

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