The Therapeutic Potential of ADSC-Secreted LEFTY2 in Treating Alzheimer's Disease.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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