The proliferation/migration ability mediated by CD151/PI3K/AKT pathway determines the therapeutic effect of hUC-MSCs transplantation on rheumatoid arthritis

• Published in: Clinical and experimental hypertension (1993) Vol. 46; no. 1; p. 2366270
• Main Authors: Xia, Xuewei, Shen, Peixin, Yang, Guomei, Yao, Mengwei, Wu, Xiaofeng, Lyu, Lina, He, Yanji, Li, Zhuxin, Wang, Wei, Yang, Yi, Ao, Xiang, Xia, Chuanjiang, Chen, Zhuo, Xu, Xiang
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 31.12.2024
• Subjects: Animals; Arthritis, Experimental - metabolism; Arthritis, Experimental - therapy; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - therapy; CD151; Cell Movement; Cell Proliferation; hUC-MSCs transplantation; Humans; IFN-γ; Interferon-gamma - metabolism; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred DBA; migration; Phosphatidylinositol 3-Kinases - metabolism; proliferation; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Umbilical Cord - cytology; migration; hUC-MSCs transplantation; IFN-γ; CD151; proliferation
• ISSN: 1064-1963; 1525-6006
• DOI: 10.1080/10641963.2024.2366270

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. 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. 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). 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.