Year: 2025
Type: article
Abstract: Adipose-derived mesenchymal stem cells (ADSCs) have exhibited promising therapeutic potential in Alzheimer's disease (AD), although the underlying mechanisms remain poorly understood. Previously established Alzheimer's disease neuron models derived from Ts21-induced pluripotent stem cells (Ts21-iPSCs) have been shown to exhibit progressive amyloid beta accumulation during neuronal differentiation. In this study, we employed a Transwell co-culture system to investigate the interaction between neurons derived from Ts21-iPSCs and ADSCs. Our findings revealed that co-culture with ADSCs significantly enhanced the survival rate of AD neurons. Proteomics analysis identified significant upregulation of left-right determination factor 2 (LEFTY2) protein in the co-culture medium. Supplementation with 2 nM LEFTY2 markedly improved the survival and growth of AD neurons. Furthermore, LEFTY2 effectively downregulates the expression of apolipoprotein E4 and amyloid beta 1-42, along with attenuating phosphorylated tau231 levels in AD neurons. These results suggest the potential of LEFTY2 as a promising therapeutic candidate for Alzheimer's disease.
DOI: 10.3390/ijms26073382
Authors: Wei Wuli, Hsueh-Hui Yang, Tzyy-Wen Chiou, Peng Yeong Woon, Yue-Xuan Xu, Cynthia Tjandra, Ivan Wijaya, Horng-Jyh Harn, Shinn-Zong Lin
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: G1870603189, G3239552315
OpenAlex ID: W4409161899