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多指畸形患儿与掌指关节骨关节炎成人骨髓间充质干细胞的增殖与分化潜能。

Proliferation and Differentiation Potential of Bone Marrow-Derived Mesenchymal Stem Cells From Children With Polydactyly and Adults With Basal Joint Arthritis.

机构信息

Department of Orthopedic Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan.

Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei.

出版信息

Cell Transplant. 2024 Jan-Dec;33:9636897231221878. doi: 10.1177/09636897231221878.

Abstract

This study compared the proliferation and differentiation potential of bone marrow-derived mesenchymal stem cells (BMSCs) derived from infants with polydactyly and adults with basal joint arthritis. The proliferation rate of adult and infant BMSCs was determined by the cell number changes and doubling times. The γH2AX immunofluorescence staining, age-related gene expression, senescence-associated β-galactosidase (SA-β-gal) staining were analyzed to determine the senescence state of adult and infant BMSCs. The expression levels of superoxide dismutases (SODs) and genes associated with various types of differentiation were measured using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Differentiation levels were evaluated through histochemical and immunohistochemical staining. The results showed that infant BMSCs had a significantly higher increase in cell numbers and faster doubling times compared with adult BMSCs. Infant BMSCs at late stages exhibited reduced γH2AX expression and SA-β-gal staining, indicating lower levels of senescence. The expression levels of senescence-related genes (, , and ) in infant BMSCs were also lower than in adult BMSCs. In addition, infant BMSCs demonstrated higher antioxidative ability with elevated expression of , , and compared with adult BMSCs. In terms of differentiation potential, infant BMSCs outperformed adult BMSCs in chondrogenesis, as indicated by higher expression levels of chondrogenic genes (, , and ) and positive immunohistochemical staining. Moreover, differentiated cells derived from infant BMSCs exhibited significantly higher expression levels of osteogenic, tenogenic, hepatogenic, and neurogenic genes compared with those derived from adult BMSCs. Histochemical and immunofluorescence staining confirmed these findings. However, adult BMSCs showed lower adipogenic differentiation potential compared with infant BMSCs. Overall, infant BMSCs demonstrated superior characteristics, including higher proliferation rates, enhanced antioxidative activity, and greater differentiation potential into various lineages. They also exhibited reduced cellular senescence. These findings, within the context of cellular differentiation, suggest potential implications for the use of allogeneic BMSC transplantation, emphasizing the need for further investigation.

摘要

这项研究比较了来自多指婴儿和基底关节关节炎成人的骨髓间充质干细胞(BMSCs)的增殖和分化潜力。通过细胞数量变化和倍增时间来确定成人和婴儿 BMSC 的增殖率。通过γH2AX 免疫荧光染色、与年龄相关的基因表达、衰老相关的β-半乳糖苷酶(SA-β-半乳糖苷)染色分析来确定成人和婴儿 BMSC 的衰老状态。使用实时定量聚合酶链反应(RT-qPCR)测量超氧化物歧化酶(SOD)和与各种分化类型相关的基因的表达水平。通过组织化学和免疫组织化学染色评估分化水平。结果表明,与成人 BMSC 相比,婴儿 BMSC 的细胞数量增加得更快,倍增时间也更快。晚期婴儿 BMSC 的γH2AX 表达和 SA-β-半乳糖苷染色减少,表明衰老程度较低。婴儿 BMSC 中与衰老相关的基因(、和)的表达水平也低于成人 BMSC。此外,与成人 BMSC 相比,婴儿 BMSC 具有更高的抗氧化能力,SOD1、SOD2 和 HO-1 的表达水平更高。在分化潜力方面,婴儿 BMSC 在软骨形成方面优于成人 BMSC,软骨形成基因(、和)的表达水平更高,免疫组织化学染色也呈阳性。此外,与成人 BMSC 分化而来的细胞相比,来源于婴儿 BMSC 的分化细胞表达更高水平的成骨、腱、肝和神经基因。组织化学和免疫荧光染色证实了这些发现。然而,与婴儿 BMSC 相比,成人 BMSC 的脂肪生成分化潜力较低。总的来说,婴儿 BMSC 表现出更高的特性,包括更高的增殖率、增强的抗氧化活性和更大的向各种谱系分化的潜力。它们还表现出较低的细胞衰老。这些发现提示着同种异体 BMSC 移植的潜在应用,强调了进一步研究的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5cf/10762874/730b733af967/10.1177_09636897231221878-fig1.jpg

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