Comparative assessment of chondral defect repair using human bone marrow- and adipose tissue-derived mesenchymal stem cells, adult and foetal articular cartilage-derived chondrocytes, and chondroprogenitors: an ex-vivo model.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnology Letters Pub Date : 2025-01-08 DOI:10.1007/s10529-024-03558-0

Elizabeth Vinod, Ganesh Parasuraman, Jeya Lisha J, Jithu James Varghese, Abel Livingston, Grace Rebekah, Deepak Vinod Francis, Solomon Sathishkumar, Alfred Job Daniel, Boopalan Ramasamy

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Abstract

Purpose: Cartilage repair necessitates adjunct therapies such as cell-based approaches, which commonly use MSCs and chondrocytes but is limited by the formation of fibro-hyaline cartilage. Articular cartilage-derived chondroprogenitors(CPs) offer promise in overcoming this, as they exhibit higher chondrogenic and lower hypertrophic phenotypes. The study aimed to compare the efficacy of various cell types derived from adult and foetal cartilage suspended in platelet-rich plasma(PRP) in repairing chondral defects in an Ex-vivo Osteochondral Unit(OCU) model.

Methods: In-vitro characterization of the cells included growth kinetics, FACS, qRT-PCR, and multilineage differentiation potential using histology and GAG analysis. Ex-vivo human OCUs with chondral defects containing the different cells in PRP were cultured and subjected to analysis for matrix and collagen staining.

Results: The ex-vivo OCU analysis, in terms of defect repair, showed that adult chondrocytes, sorted-CPs, and foetal MCPs displayed better host integration and filling. The In-vitro analysis of adult chondrocytes displayed greater chondrogenic genes ACAN and COL2A1 expression, with sorted-CPs also showing higher levels of ACAN. In terms of accumulation of extracellular matrix uptake evident by Safranin O staining and collagen type II fibrillar uptake, the AD-MSCs, BM-MSCs, and sorted CPs outperformed the other groups. BM-MSCs also showed corroborative higher CD146 levels, however, the gene analysis of the AD-MSCs showed a high hypertrophic tendency in terms of its COL1A1 and RUNX2 expression.

Conclusion: Sorted chondroprogenitors outperformed both in terms of filling and hyaline-like repair, with AD-MSC and BM-MSC groups also achieving functional cartilage of a hyaline nature, warranting further evaluation using in-vivo and clinical studies.

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使用人骨髓和脂肪组织来源的间充质干细胞、成人和胎儿关节软骨来源的软骨细胞和软骨祖细胞修复软骨缺陷的比较评估：离体模型。

目的：软骨修复需要辅助治疗，如基于细胞的方法，通常使用间充质干细胞和软骨细胞，但受纤维透明软骨形成的限制。关节软骨来源的软骨祖细胞（CPs）有望克服这一问题，因为它们表现出更高的软骨性和更低的肥厚表型。本研究旨在比较不同类型的成人和胎儿软骨细胞悬浮在富血小板血浆（PRP）中修复离体骨软骨单元（OCU）模型软骨缺损的效果。方法：体外鉴定细胞包括生长动力学、FACS、qRT-PCR和多系分化潜力，采用组织学和GAG分析。培养含不同PRP细胞的离体人软骨缺损OCUs，进行基质和胶原染色分析。结果：离体OCU分析显示，在缺陷修复方面，成人软骨细胞、分选的cps和胎儿MCPs表现出更好的宿主整合和填充。成人软骨细胞的体外分析显示出更大的成软骨基因ACAN和COL2A1的表达，分拣的cps也显示出更高水平的ACAN。在细胞外基质摄取的积累（由Safranin O染色和II型胶原纤维摄取）方面，AD-MSCs、BM-MSCs和分选的CPs优于其他组。BM-MSCs也显示出更高的CD146水平，然而，AD-MSCs的基因分析显示COL1A1和RUNX2的表达有较高的增厚倾向。结论：分选的软骨祖细胞在填充和透明样修复方面都表现出色，AD-MSC和BM-MSC组也实现了透明质的功能性软骨，需要通过体内和临床研究进一步评估。

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来源期刊

Biotechnology Letters 工程技术-生物工程与应用微生物

CiteScore

5.90

自引率

3.70%

发文量

108

审稿时长

1.2 months

期刊介绍： Biotechnology Letters is the world’s leading rapid-publication primary journal dedicated to biotechnology as a whole – that is to topics relating to actual or potential applications of biological reactions affected by microbial, plant or animal cells and biocatalysts derived from them. All relevant aspects of molecular biology, genetics and cell biochemistry, of process and reactor design, of pre- and post-treatment steps, and of manufacturing or service operations are therefore included. Contributions from industrial and academic laboratories are equally welcome. We also welcome contributions covering biotechnological aspects of regenerative medicine and biomaterials and also cancer biotechnology. Criteria for the acceptance of papers relate to our aim of publishing useful and informative results that will be of value to other workers in related fields. The emphasis is very much on novelty and immediacy in order to justify rapid publication of authors’ results. It should be noted, however, that we do not normally publish papers (but this is not absolute) that deal with unidentified consortia of microorganisms (e.g. as in activated sludge) as these results may not be easily reproducible in other laboratories. Papers describing the isolation and identification of microorganisms are not regarded as appropriate but such information can be appended as supporting information to a paper. Papers dealing with simple process development are usually considered to lack sufficient novelty or interest to warrant publication.