The Chondrogenic Potential of Mesenchymal Cells and Chondrocytes from Osteoarthritic Subjects

Agar, Gabriel; Blumenstein, Sara; Bar-Ziv, Yaron; Kardosh, Rami; Schrift-Tzadok, Michal; Gal-Levy, Ronit; Fischler, Tali; Goldschmid, Revital; Yayon, Avner

doi:10.1177/1947603510380899

Cited by 16 publications

(16 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…High patient-to-patient variability in the chondrogenic potential of both OACs and MSCs demonstrates the importance of using biological material either from the same subject or a large donor population. 70 In our study, we were able to use paired samples of MSCs and OACs, obtained from two donors. Additionally, we tested a set of mismatched biological samples of OACs (patient) and MSCs (commercially available cells).…”

Section: Mscs As a Potential Cell Source For In Vitro Testing Of Drugsmentioning

confidence: 99%

Testing the potency of anti‐TNF‐α and anti‐IL‐1β drugs using spheroid cultures of human osteoarthritic chondrocytes and donor‐matched chondrogenically differentiated mesenchymal stem cells

Žigon-Branc

Barlič

Knežević

et al. 2018

Biotechnology Progress

View full text Add to dashboard Cite

Inflammation plays a major role in progression of rheumatoid arthritis, a disease treated with antagonists of tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). New in vitro testing systems are needed to evaluate efficacies of new anti-inflammatory biological drugs, ideally in a patient-specific manner. To address this need, we studied microspheroids containing 10,000 human osteoarthritic primary chondrocytes (OACs) or chondrogenically differentiated mesenchymal stem cells (MSCs), obtained from three donors. Hypothesizing that this system can recapitulate clinically observed effects of anti-inflammatory drugs, spheroids were exposed to TNF-α, IL-1β, or to supernatant containing secretome from activated macrophages (MCM). The anti-inflammatory efficacies of anti-TNF-α biologicals adalimumab, infliximab, and etanercept, and the anti-IL-1β agent anakinra were assessed in short-term microspheroid and long-term macrospheroid cultures (100,000 OACs). While gene and protein expressions were evaluated in microspheroids, diameters, amounts of DNA, glycosaminoglycans, and hydroxiproline were measured in macrospheroids. The tested drugs significantly decreased the inflammation induced by TNF-α or IL-1β. The differences in potency of anti-TNF-α biologicals at 24 h and 3 weeks after their addition to inflamed spheroids were comparable, showing high predictability of short-term cultures. Moreover, the data obtained with microspheroids grown from OACs and chondrogenically differentiated MSCs were comparable, suggesting that MSCs could be used for this type of in vitro testing. We propose that in vitro gene expression measured after the first 24 h in cultures of chondrogenically differentiated MSCs can be used to determine the functionality of anti-TNF-α drugs in personalized and preclinical studies. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1045-1058, 2018.

show abstract

Section: Mscs As a Potential Cell Source For In Vitro Testing Of Drugsmentioning

confidence: 99%

Testing the potency of anti‐TNF‐α and anti‐IL‐1β drugs using spheroid cultures of human osteoarthritic chondrocytes and donor‐matched chondrogenically differentiated mesenchymal stem cells

Žigon-Branc

Barlič

Knežević

et al. 2018

Biotechnology Progress

View full text Add to dashboard Cite

show abstract

“…An earlier study reported declined potential of CPCs from OA patients [5]. However, another study described that adult CPCs, particularly those from moderately affected regions of the osteoarthritic joints, exhibit superior chondrogenic potential [37]. In addition, the independent studies pursued by Xia et al and Mantripragada et al demonstrated that CPCs from the degraded cartilages of the medial condyle and relatively normal cartilages of the lateral side showed similar chondrogenic potential [14,18,19].…”

Section: Discussionmentioning

confidence: 99%

Biological potential alterations of migratory chondrogenic progenitor cells during knee osteoarthritic progression

et al. 2020

View full text Add to dashboard Cite

Background: Although increasing studies have demonstrated that chondrogenic progenitor cells (CPCs) remain present in human osteoarthritic cartilage, the biological alterations of the CPCs from the less diseased lateral tibial condyle and the more diseased medial condyle of same patient remain to be investigated. Methods: CPCs were isolated from paired grade 1-2 and grade 3-4 osteoarthritic cartilage by virtue of cell migratory capacities. The cell morphology, immunophenotype, self-renewal, multi-differentiation, and cell migration of these CPCs were evaluated. Additionally, the distributions of CD105 + /CD271 + cells in OA osteochondral specimen were determined. Furthermore, a high-throughput mRNA sequencing was performed. Results: Migratory CPCs (mCPCs) robustly outgrew from mildly collagenases-digested osteoarthritic cartilages. The mCPCs from grade 3-4 cartilages (mCPCs, grades 3-4) harbored morphological characteristics, cell proliferation, and colony formation capacity that were similar to those of the mCPCs from the grade 1-2 OA cartilages (mCPCs, grades 1-2). However, the mCPCs (grades 3-4) highly expressed CD271. In addition, the mCPCs (grades 3-4) showed enhanced osteo-adipogenic activities and decreased chondrogenic capacity. Furthermore, the mCPCs (grades 3-4) exhibited stronger cell migration in response to osteoarthritis synovial fluids. More CD105 + /CD271 + cells resided in grade 3-4 articular cartilages. Moreover, the results of mRNA sequencing showed that mCPCs (grades 3-4) expressed higher migratory molecules. Conclusions: Our data suggest that more mCPCs (grades 3-4) migrate to injured articular cartilages but with enhanced osteo-adipogenic and decreased chondrogenic capacity, which might explain the pathological changes of mCPCs during the progression of OA from early to late stages. Thus, these dysfunctional mCPCs might be optional cell targets for OA therapies.

show abstract

“…As for chondrogenic capacity, an earlier study reported declined potential of CPCs from OA patients, and upregulation of the osteogenic transcription factor RUNX-2 decreased the expression of the chondrogenic transcription factor Sox-9 [5]. Another study described that adult CPCs, particularly those from moderately affected regions of the osteoarthritic joints, demonstrate superior chondrogenic potential [32]. In addition, the independent studies pursued by the medial condyle and relatively normal cartilage on the lateral side from OA patients showed comparable chondrogenic potential [13,17,18].…”

Section: Discussionmentioning

confidence: 99%

Biological Potential Alterations of Migratory Chondrogenic Progenitor Cells during Knee Osteoarthritic Progression

Wang

Zhao

Wang

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Although studies have demonstrated that chondrogenic progenitor cells (CPCs) remain present in human osteoarthritic cartilage, the heterogeneity of CPCs subpopulations, the biological alterations of CPCs, and their contributions to the progression of osteoarthritis remain to be investigated. Methods: CPCs were isolated from paired grade 1-2 and grade 3-4 osteoarthritic cartilage by virtue of cell migratory capacities. The cell morphology, immunophenotype, self-renewal, multidifferentiation, and cell migration of these CPCs were evaluated. Additionally, the distributions of CPCs in articular cartilage were determined by immuno-histochemical staining. Furthermore, a high-through mRNA sequencing was performed to explore the underlying mechanisms. Results: Migratory CPCs (mCPCs) robustly outgrew from collagenases-digested osteoarthritic cartilages for 2 weeks after the initial culture. The mCPCs from grade 3-4 cartilages (mCPCs, grade 3-4) harbored morphological characteristics, cell proliferation and colony formation capacity that were similar to those of the mCPCs from the grade 1-2 cartilages (mCPCs, grade 1-2). However, the mCPCs (grade 3-4) highly expressed CD271. In addition, the mCPCs (grade 3-4) showed enhanced osteo-adipogenic activities and decreased chondrogenic capacity. Furthermore, the mCPCs (grade 3-4) exhibited stronger cell migration in response to osteoarthritis synovial fluids. More CD105+ cells resided in grade 3-4 superficial articular cartilages. Moreover, the results of mRNA sequencing showed that mCPCs (grade 3-4) expressed higher migratory molecules. Conclusions: Our data suggest that more mCPCs (grade 3-4) migrate to injured articular cartilages but with decreased cartilage-repairing capacity, which might accelerate cartilage degradation. Thus, these dysfunctional mCPCs might be a novel cell target to alleviate cartilage lesions.

show abstract

The Chondrogenic Potential of Mesenchymal Cells and Chondrocytes from Osteoarthritic Subjects

Cited by 16 publications

References 32 publications

Testing the potency of anti‐TNF‐α and anti‐IL‐1β drugs using spheroid cultures of human osteoarthritic chondrocytes and donor‐matched chondrogenically differentiated mesenchymal stem cells

Testing the potency of anti‐TNF‐α and anti‐IL‐1β drugs using spheroid cultures of human osteoarthritic chondrocytes and donor‐matched chondrogenically differentiated mesenchymal stem cells

Biological potential alterations of migratory chondrogenic progenitor cells during knee osteoarthritic progression

Biological Potential Alterations of Migratory Chondrogenic Progenitor Cells during Knee Osteoarthritic Progression

Contact Info

Product

Resources

About