Brain-derived neurotrophic factor modified human umbilical cord mesenchymal stem cells-derived cholinergic-like neurons improve spatial learning and memory ability in Alzheimer’s disease rats

2019 ◽  
Vol 1710 ◽  
pp. 61-73 ◽  
Author(s):  
Weiwei Hu ◽  
Zehua Feng ◽  
Jun Xu ◽  
Zhi Jiang ◽  
Meijiang Feng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Learning And Memory ◽  
Umbilical Cord ◽  
Spatial Learning ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Spatial Learning And Memory ◽  
Human Umbilical Cord ◽  
Memory Ability

scholarly journals Brain-Derived Neurotrophic Factor Secreting Human Mesenchymal Stem Cells Improve Outcomes in Rett Syndrome Mouse Models

2021 ◽  
Vol 15 ◽  
Author(s):  
Hyo Jeong Kim ◽  
Delger Bayarsaikhan ◽  
Jaesuk Lee ◽  
Govigerel Bayarsaikhan ◽  
Bonghee Lee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rett Syndrome ◽  
Neurotrophic Factor ◽  
Neurodevelopmental Disorder ◽  
Neuronal Cell ◽  
Brain Derived Neurotrophic Factor ◽  
The Body ◽  
Human Umbilical Cord

Rett syndrome (RTT) is a severe X-linked dominant neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene; MeCP2 regulates the expression of brain-derived neurotrophic factor (BDNF) and increasing BDNF levels ameliorates RTT symptoms. However, the clinical application of BDNF is limited, because of its short half-life and low penetrance across the blood-brain barrier. In this study, we generated BDNF-secreting mesenchymal stem cells (MSCs) from the human umbilical cord cells, using CRISPR-Cas9. We studied the effects of BDNF-MSCs in MECP2 knockout and MECP2-deficient mice. BDNF-MSCs upregulated the expression of BDNF, pAKT, and pERK1/2 and downregulated that of pp38, both in vitro and in vivo. In our in vivo experiments, BDNF-MSCs increased the body and brain weights in mice. BDNF-MSCs increased the neuronal cell numbers in the hippocampus, cortex, and striatum; in addition, they increased the number of synapses. BDNF-MSCs upregulated BDNF and the activity of BDNF downstream effectors, such as pAKT and pERK 1/2; this upregulation was persistent. In conclusion, BDNF-MSCs generated using CRISPR-Cas9 could be a therapeutic strategy for treating RTT.

scholarly journals Spatial learning and memory of young and aging rats following injection with human Wharton’s jelly‐mesenchymal stem cells

2021 ◽  
Vol 26 (2) ◽  
pp. 91
Author(s):  
Berry Juliandi ◽  
Wildan Mubarok ◽  
Dian Anggraini ◽  
Arief Boediono ◽  
Mawar Subangkit ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Neuronal Apoptosis ◽  
Spatial Learning And Memory ◽  
Post Injection ◽  
Aging Rats ◽  
Wharton's Jelly ◽  
Young Rats

Human Wharton’s jelly‐mesenchymal stem cells (hWJ‐MSC) are an emerging potential source of stem cells derived from the umbilical cord. Previous studies have shown their potential as treatment for traumatic brain injury and Parkinson’s disease. However, no study has yet investigated the effect of hWJ‐MSC injections in countering spatial learning and memory impairment in aging rats. The effect of hWJ‐MSC injection on young rats is also unknown. The objective of this research was to analyze the effect of an hWJ‐MSC injection on spatial learning, memory, density of putative neural progenitor cells (pNPC), and neuronal apoptosis in the dentate gyrus (DG) of young and aging rats. Injection of hWJ‐MSC did not change spatial learning and memory in young rats until two months post‐injection. This might be due to retained pNPC density and neuronal apoptosis in the DG of young rats after injection of hWJ‐MSC. In contrast, injection of hWJ‐MSC promoted both spatial learning and memory in aging rats, a finding that might be attributable to the increased pNPC density and attenuated neuronal apoptosis in DG of aging rats during the two months post‐injection. Our study suggests that a single injection of hWJ‐MSC might be sufficient to promote improvement in long‐term learning and memory in aging rats.

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