Transplanting human umbilical cord mesenchymal stem cells and hyaluronate hydrogel repairs cartilage of osteoarthritis in the minipig model

et al. 2021

Aging

Autologous chondrocyte implantation (ACI) is an effective method for treating chronic articular cartilage injury and degeneration; however, it requires large numbers of hyaline chondrocytes, and human hyaline chondrocytes often undergo dedifferentiation in vitro . Moreover, although long non-coding RNAs (lncRNAs) regulate gene expression in many pathological and physiological processes, their role in human hyaline chondrocyte dedifferentiation remains unclear. Here, we examined lncRNA and mRNA expression profiles in human hyaline chondrocyte dedifferentiation using microarray analysis. Among the many lncRNAs and mRNAs that showed differential expression, lncRNA AP001505.9 (ENST00000569966) was significantly downregulated in chondrocytes after dedifferentiation. We next performed gene ontology, pathway, and CNC (coding-non-coding gene co-expression) analyses to investigate potential regulatory mechanisms for AP001505.9. Pellet cultures were then used to redifferentiate dedifferentiated chondrocytes, and AP001505.9 expression was upregulated after redifferentiation. Finally, both in vitro and in vivo experiments demonstrated that AP001505.9 overexpression inhibited dedifferentiation of chondrocytes. This study characterizes lncRNA expression profiles in human hyaline chondrocyte dedifferentiation, thereby identifying new potential mechanisms of chondrocyte dedifferentiation worthy of further investigation.

Section: Discussionmentioning

confidence: 99%

Overexpression of long non-coding RNA AP001505.9 inhibits human hyaline chondrocyte dedifferentiation

Chen

et al. 2021

Aging

“…Articular cartilage injury and degeneration brings serious economic burden to their families and the society (30). The rise of ACI technology has brought hope for rehabilitation of these patients and is currently considered to be the best treatment for cartilage injury (31).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Long Non-Coding RNA AP001505.9 Inhibits Dedifferentiation in Human Hyaline Chondrocyte

Chen

et al. 2020

Preprint

Background: Autologous chondrocyte implantation (ACI) requires a large number ofhuman hyaline chondrocytes. Unfortunately, human hyaline chondrocytes oftenundergo dedifferentiation in vitro. Long non-coding RNAs (lncRNA) play aregulatory role in gene expression in many pathological and physiological processes.However, their role in human hyaline chondrocyte dedifferentiation remains unclear.This study aimed to investigate the expression profiles of lncRNAs in human hyalinechondrocyte dedifferentiation.Methods: Human hyaline chondrocytes were cultured in vitro and screened for theoccurrence of dedifferentiation using real-time quantitative PCR (qPCR),immunofluorescence, and western blotting. The expression profiles of lncRNAs andmRNAs during dedifferentiation were analyzed by microarray analysis and real-timeqPCR. We used pellet culture to redifferentiate chondrocytes and the expression ofrelated lncRNAs were assessed. The function of lncRNA AP001505.9(ENST00000569966) was determined by overexpression, fluorescence in situhybridization, competing endogenous RNA (ceRNA) analysis, and double luciferaselabeling.Results: We probed human hyaline chondrocytes dedifferentiation and identified 334upregulated and 381 downregulated lncRNAs. The expression of downregulatedlncRNA AP001505.9 in dedifferentiation was reversed by pellet culture. Theoverexpression of AP001505.9 inhibited dedifferentiation by promoting theexpression of SRY-Box transcription factor 9 (SOX-9) and inhibiting the expressionof type I collagen (COL1) both in vitro and in vivo.Conclusion: This study reveals for the first time the expression profiles of lncRNAsin human hyaline chondrocyte dedifferentiation, thereby providing a new perspectivefor exploring the potential mechanism of chondrocyte dedifferentiation.

“…The possibility of such missing data is higher in meta-analysis when results from studies with acceptable differences in design and purpose are pooled to form a database. In our database, for example, the osteochondral defect studies took the area of defect as a common critical data for evaluating the severity of injury [ 14 , 17 ]. However, this information was not always presented in osteoarthritis studies due to difficulties in precisely measuring defect area with complicated geometry [ 25 , 48 ].…”

Section: Methodsmentioning

confidence: 99%

Machine learning to predict mesenchymal stem cell efficacy for cartilage repair

et al. 2020

PLoS Comput Biol

Inconsistent therapeutic efficacy of mesenchymal stem cells (MSCs) in regenerative medicine has been documented in many clinical trials. Precise prediction on the therapeutic outcome of a MSC therapy based on the patient's conditions would provide valuable references for clinicians to decide the treatment strategies. In this article, we performed a metaanalysis on MSC therapies for cartilage repair using machine learning. A small database was generated from published in vivo and clinical studies. The unique features of our neural network model in handling missing data and calculating prediction uncertainty enabled precise prediction of post-treatment cartilage repair scores with coefficient of determination of 0.637 ± 0.005. From this model, we identified defect area percentage, defect depth percentage, implantation cell number, body weight, tissue source, and the type of cartilage damage as critical properties that significant impact cartilage repair. A dosage of 17 − 25 million MSCs was found to achieve optimal cartilage repair. Further, critical thresholds at 6% and 64% of cartilage damage in area, and 22% and 56% in depth were predicted to significantly compromise on the efficacy of MSC therapy. This study, for the first time, demonstrated machine learning of patient-specific cartilage repair post MSC therapy. This approach can be applied to identify and investigate more critical properties involved in MSC-induced cartilage repair, and adapted for other clinical indications.