Advanced Science Study Highlights HGF-Mediated Therapeutic Potential of hUC-MSCs in Alzheimer’s Disease

On July 6, 2020, the international academic journal Advanced Science published online the latest research findings by the Academy of Military Medical Sciences of the Academy of Military Sciences and the South China Institute of Stem Cell and Regenerative Medicine, titled “HGF mediates clinical-grade human umbilical cord-derived mesenchymal stem cells improved functional recovery in a senescence-accelerated mouse model of Alzheimer’s disease.” Professor Pei Xuetao and Professor Yue Wen served as co-corresponding authors, with Dr. Jia Yali as the first author. The study demonstrated that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess the capability to repair damaged neuronal cells. These cells can regulate tau protein phosphorylation via the HGF-cMet-AKT-GSK3β signaling pathway, thereby significantly improving learning, memory, and cognitive functions in animal models of Alzheimer’s disease (AD).

Stem cell intervention for age-related cognitive decline is one of the key research focuses of this team. Age-related cognitive decline is primarily categorized into two types: physiological and pathological. The former, characterized by a reduction in cognitive abilities, is defined as "cognitive aging," while the latter is associated with the onset of neurodegenerative diseases such as Alzheimer’s disease (AD). Previously, the team provided the first evidence that human umbilical cord mesenchymal stem cells (hUC-MSCs) can improve cognitive function in the aging brain (related findings were published in the international academic journal *Cell Death and Disease*, DOI: 10.1038/cddis.2017.316). In this latest study, Jia Yali and colleagues further confirmed that hUC-MSCs, as a type of young stem cell, hold promise as an adjunctive therapy for intervening in or reversing Alzheimer’s disease. The study results indicate that hUC-MSCs can effectively reverse structural alterations and functional decline in the AD brain, significantly enhancing cognitive abilities in SAMP8 mice (an accelerated aging mouse model of AD). Furthermore, the study demonstrated that hepatocyte growth factor (HGF), a core factor secreted by hUC-MSCs, plays a crucial regulatory role in the process by which hUC-MSCs repair damaged neural cells and improve cognition in the AD brain. These effects include inhibiting hyperphosphorylation of tau protein, ameliorating neurofibrillary tangles, reducing the loss of neuronal dendritic spines, and enhancing synaptic plasticity. Further analysis revealed that some of the functions of hUC-MSCs are mediated through the secretion of HGF, which activates the cMet-AKT-GSK3β signaling pathway.

In summary, hUC-MSCs exert therapeutic effects on Alzheimer’s disease (AD) by secreting functional cytokines such as hepatocyte growth factor (HGF). This study demonstrates that young stem cells hold significant value in the prevention and treatment of AD and other age-related neurodegenerative diseases. Currently, clinical studies conducted by this team in collaboration with hospitals to treat AD are being vigorously advanced.

Original Source:

1. Yali Jia, et al. HGF mediates clinical-grade human umbilical cord-derived mesenchymal stem cells improved functional recovery in a senescence-accelerated mouse model of Alzheimer's disease. Advanced Science. 2020. 1903809. DOI: 10.1002/advs.201903809.

https://doi.org/10.1002/advs.201903809

2. Ning Cao, et al. Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse cognitive aging via improving synaptic plasticity and endogenous neurogenesis. Cell Death Dis. 2017 Aug 10;8(8):e2996. DOI: 10.1038/cddis.2017.316.