关键词: CD151 IFN-γ hUC-MSCs transplantation migration proliferation

Mesh : Animals Cell Proliferation Arthritis, Rheumatoid / therapy metabolism Cell Movement Mice Mesenchymal Stem Cells / metabolism Proto-Oncogene Proteins c-akt / metabolism Mesenchymal Stem Cell Transplantation / methods Phosphatidylinositol 3-Kinases / metabolism Humans Mice, Inbred DBA Signal Transduction Interferon-gamma / metabolism Umbilical Cord / cytology Arthritis, Experimental / therapy metabolism Male

来  源:   DOI:10.1080/10641963.2024.2366270

Abstract:
UNASSIGNED: To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment.
UNASSIGNED: The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively.
UNASSIGNED: IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs).
UNASSIGNED: IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.
摘要:
阐明人脐带间充质干细胞(hUC-MSC)的增殖和迁移能力决定其在类风湿性关节炎治疗中的治疗功效的潜在机制。
利用DBA/1J小鼠建立胶原诱导的RA(CIA)小鼠模型并验证用CD151siRNA转染的hUC-MSC的治疗功效。RNA-seq,QT-PCR和蛋白质印迹用于评估PI3K/AKT途径的mRNA和蛋白质水平。分别。
IFN-γ显著增强hUC-MSCs的增殖和迁移能力,上调与细胞增殖和迁移相关的基因CD151的表达。通过CD151siRNA处理实现了这种作用的有效抑制。然而,IFN-γ不影响hUC-MSCs分化或细胞表面标志物的变化。此外,与空载体治疗(siRNA-NC-hUC-MSCs)相比,CD151干扰的hUC-MSCs(siRNA-CD151-hUC-MSCs)移植导致CIA小鼠脚趾定植减少,治疗效果更差.
IFN-γ通过CD151/PI3K/AKT途径促进hUC-MSCs的增殖和迁移。发现siRNA-CD151-hUC-MSC的治疗功效劣于siRNA-NC-hUC-MSC的治疗功效。
公众号