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间充质干细胞中 和β转录因子的共同调控使椎间盘退变得以再生。 （注：原文中“and β transcription factors”前的“ ”处内容缺失，翻译可能会因信息不完整有偏差）

Co-regulation of and β transcription factors in mesenchymal stem cells regenerated the intervertebral disc degeneration.

作者信息

Khalid Shumaila, Ekram Sobia, Ramzan Faiza, Salim Asmat, Khan Irfan

机构信息

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Sindh, Pakistan.

出版信息

Front Med (Lausanne). 2023 Mar 17;10:1127303. doi: 10.3389/fmed.2023.1127303. eCollection 2023.

DOI:10.3389/fmed.2023.1127303
PMID:37007782
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10063891/
Abstract

BACKGROUND

Intervertebral disc (IVD) shows aging and degenerative changes earlier than any other body connective tissue. Its repair and regeneration provide a considerable challenge in regenerative medicine due to its high degree of infrastructure and mechanical complexity. Mesenchymal stem cells, due to their tissue resurfacing potential, represent many explanatory pathways to regenerate a tissue breakdown.

METHODS

This study was undertaken to evaluate the co-regulation of and β in differentiating human umbilical cord mesenchymal stem cells (hUC-MSC) into chondrocytes. The combinatorial impact of and β on hUC-MSCs was examined by gene expression and immunocytochemical staining. In , an animal model of IVD degeneration was established under a fluoroscopic guided system through needle puncture of the caudal disc. Normal and transfected MSCs were transplanted. Oxidative stress, pain, and inflammatory markers were evaluated by qPCR. Disc height index (DHI), water content, and gag content were analyzed. Histological examinations were performed to evaluate the degree of regeneration.

RESULTS

hUC-MSC transfected with +β showed a noticeable morphological appearance of a chondrocyte, and highly expressed chondrogenic markers (ββ, and type II collagens) after transfection. Histological observation demonstrated that cartilage regeneration, extracellular matrix synthesis, and collagen remodeling were significant upon staining with H&E, Alcian blue, and Masson's trichrome stain on day 14. Additionally, oxidative stress, pain, and inflammatory markers were positively downregulated in the animals transplanted with and β transfected MSCs.

CONCLUSION

These findings indicate that the combinatorial effect of and β substantially accelerates the chondrogenesis in hUC-MSCs. Cartilage regeneration and matrix synthesis were significantly enhanced. Therefore, a synergistic effect of and β could be an immense therapeutic combination in the tissue engineering of cartilaginous joint bio-prostheses and a novel candidate for cartilage stabilization.

摘要

背景

椎间盘（IVD）比身体其他任何结缔组织更早出现衰老和退行性变化。由于其高度的结构和机械复杂性，其修复和再生在再生医学中是一项巨大挑战。间充质干细胞因其组织修复潜力，为组织损伤再生提供了多种解释途径。

方法

本研究旨在评估在将人脐带间充质干细胞（hUC-MSC）分化为软骨细胞过程中 和β的共同调节作用。通过基因表达和免疫细胞化学染色检测 和β对hUC-MSCs的联合影响。在 中，通过尾椎间盘穿刺在荧光镜引导系统下建立IVD退变动物模型。移植正常和转染的间充质干细胞。通过qPCR评估氧化应激、疼痛和炎症标志物。分析椎间盘高度指数（DHI）、含水量和糖胺聚糖含量。进行组织学检查以评估再生程度。

结果

用 +β转染的hUC-MSC显示出明显的软骨细胞形态外观，转染后高表达软骨生成标志物（ββ和II型胶原）。组织学观察表明，在第14天用苏木精-伊红染色、阿尔辛蓝染色和马森三色染色时，软骨再生、细胞外基质合成和胶原重塑显著。此外，在移植了 和β转染的间充质干细胞的动物中，氧化应激、疼痛和炎症标志物呈阳性下调。

结论

这些发现表明 和β的联合作用显著加速了hUC-MSCs的软骨生成。软骨再生和基质合成显著增强。因此， 和β的协同作用可能是软骨关节生物假体组织工程中一种巨大的治疗组合，也是软骨稳定的一种新候选方法。

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