Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer’s disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis

Cui, Yuan Bo; Shan, Shan; Zhang, Chun Yan; Cao, Wei; Liu, Min; Li, Dong Peng; Lv, Ping; Xing, Qu; Qu, Rui Na; Yao, Ning; Yang, Bo; Guan, Fang Xia

doi:10.1016/j.bbr.2016.12.021

Cited by 111 publications

(85 citation statements)

References 42 publications

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“…All procedures were performed in strict accordance with the National Institutes of Health guidelines for the Care and Use of Laboratory Animals. The transgenic AD mice used in this study were described as previously described [19]. Mice were housed at 25 °C under a 12 h light/dark cycle, with free access to standard food and water.…”

Section: Methodsmentioning

confidence: 99%

Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease

Wang

Yang

et al. 2018

Behavioural Brain Research

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Mesenchymal stem cell transplantation is a promising therapeutic approach for Alzheimer’s disease (AD). However, poor engraftment and limited survival rates are major obstacles for its clinical application. Resveratrol, an activator of silent information regulator 2, homolog 1 (SIRT1), regulates cell destiny and is beneficial for neurodegenerative disorders. The present study is designed to explore whether resveratrol regulates the fate of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and whether hUC-MSCs combined with resveratrol would be efficacious in the treatment of neurodegeneration in a mouse model of AD through SIRT1 signaling. Herein, we report that resveratrol facilitates hUC-MSCs engraftment in the hippocampus of AD mice and resveratrol enhances the therapeutic effects of hUC-MSCs in this model as demonstrated by improved learning and memory in the Morris water maze, enhanced neurogenesis and alleviated neural apoptosis in the hippocampus of the AD mice. Moreover, hUC-MSCs and resveratrol jointly regulate expression of hippocampal SIRT1, PCNA, p53, ac-p53, p21, and p16. These data strongly suggests that hUC-MSCs transplantation combined with resveratrol may be an effective therapy for AD.

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Section: Methodsmentioning

confidence: 99%

Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease

Wang

Yang

et al. 2018

Behavioural Brain Research

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“…Stem cell‐based therapies can greatly impact the field of regenerative medicine. MSCs have been used in preclinical and clinical studies to treat degenerative diseases, such as AD (Cui et al, ; Han et al, ; J. Shin et al, ; X. Wang, Ma, et al, ), DDD (Ahn et al, ; Beeravolu et al, ; Pereira et al, ; Perez‐Cruet et al, ), MS (Harris et al, ; Nasri et al, ; Planchon et al, ), PD (Jamali et al, ; H. Kim, Lee, et al, ), and RDD (Mead, Amaral, & Tomarev, ), as summarized in Table . The regenerative mechanisms of transplanted MSCs for these diseases are still unclear; however, some reports have suggested that MSCs have the potential to differentiate or have paracrine effects in vivo (Lee, Choi, Cha, & Hwang, ).…”

Section: Promising Applications Of Mscsmentioning

confidence: 99%

“…Stem cell-based therapies can greatly impact the field of regenerative medicine. MSCs have been used in preclinical and clinical studies to treat degenerative diseases, such as AD (Cui et al, 2017;Han et al, 2018;X. Wang, Ma, et al, 2018), DDD (Ahn et al, 2015;Beeravolu et al, 2018;Pereira et al, 2016;Perez-Cruet et al, 2018), MS (Harris et al, 2018;Nasri et al, 2018;Planchon et al, 2018), PD (Jamali et al, 2018;H.…”

Section: Promising Applications Of Mscsmentioning

confidence: 99%

“…Alzheimer's disease (Cui et al, 2017;Han et al, 2018;X. Wang, Ma, et al, 2018) Bone and cartilage diseases (Jo et al, 2014;Kastrinaki et al, 2013) Autoimmune diseases (Xu, 2018;W.…”

Section: Promising Applications Referencementioning

confidence: 99%

“…In addition, MSCs have a paracrine effect that promotes immunomodulation as well as antiapoptotic and anti-oxidative effects, which can be helpful for treating neuromuscular pains (van Buul et al, 2014) and many other diseases (de Witte et al, 2018;Francois et al, 2013;Khubutiya, Vagabov, Temnov, & Sklifas, 2014). MSCs are also being investigated for their therapeutic potential to treat degenerative diseases and disorders such as Parkinson's disease (PD; Jamali, Ma Hattab, Amman, & Awidi, 2018; H. Kim, Lee, et al, 2018), Alzheimer's disease (AD; Cui et al, 2017;Han et al, 2018), amyotrophic lateral sclerosis (Bonafede & Mariotti, 2017), multiple sclerosis (MS; Harris et al, 2018; Nasri Ahn et al, 2015;Beeravolu et al, 2018;Perez-Cruet et al, 2018), retinal degenerative disease (RDD; Y. Wang, Zhang, Shen, Zhang, & Gu, 2018;, myocardial infarction (X. Q.…”

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confidence: 99%

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Mesenchymal stem cells: Cell therapy and regeneration potential

Brown

McKee

Bakshi

et al. 2019

J Tissue Eng Regen Med

396

268

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Rapid advances in the isolation of multipotent progenitor cells, routinely called mesenchymal stromal/stem cells (MSCs), from various human tissues and organs have provided impetus to the field of cell therapy and regenerative medicine. The most widely studied sources of MSCs include bone marrow, adipose, muscle, peripheral blood, umbilical cord, placenta, fetal tissue, and amniotic fluid. According to the standard definition of MSCs, these clonal cells adhere to plastic, express cluster of differentiation (CD) markers such as CD73, CD90, and CD105 markers, and can differentiate into adipogenic, chondrogenic, and osteogenic lineages in vitro. However, isolated MSCs have been reported to vary in their potency and self‐renewal potential. As a result, the MSCs used for clinical applications often lead to variable or even conflicting results. The lack of uniform characterization methods both in vitro and in vivo also contributes to this confusion. Therefore, the name “MSCs” itself has been increasingly questioned lately. As the use of MSCs is expanding rapidly, there is an increasing need to understand the potential sources and specific potencies of MSCs. This review discusses and compares the characteristics of MSCs and suggests that the variations in their distinctive features are dependent on the source and method of isolation as well as epigenetic changes during maintenance and growth. We also discuss the potential opportunities and challenges of MSC research with the hope to stimulate their use for therapeutic and regenerative medicine.

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HGF Mediates Clinical‐Grade Human Umbilical Cord‐Derived Mesenchymal Stem Cells Improved Functional Recovery in a Senescence‐Accelerated Mouse Model of Alzheimer's Disease

Jia

Cao²,

Zhai³

et al. 2020

Advanced Science

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Stem cells have emerged as a potential therapy for a range of neural insults, but their application in Alzheimer's disease (AD) is still limited and the mechanisms underlying the cognitive benefits of stem cells remain to be elucidated. Here, the effects of clinical‐grade human umbilical cord‐derived mesenchymal stem cells (hUC‐MSCs) on the recovery of cognitive ability in SAMP8 mice, a senescence‐accelerated mouse model of AD is explored. A functional assay identifies that the core functional factor hepatocyte growth factor (HGF) secreted from hUC‐MSCs plays critical roles in hUC‐MSC‐modulated recovery of damaged neural cells by down‐regulating hyperphosphorylated tau, reversing spine loss, and promoting synaptic plasticity in an AD cell model. Mechanistically, structural and functional recovery, as well as cognitive enhancements elicited by exposure to hUC‐MSCs, are at least partially mediated by HGF in the AD hippocampus through the activation of the cMet‐AKT‐GSK3β signaling pathway. Taken together, these data strongly implicate HGF in mediating hUC‐MSC‐induced improvements in functional recovery in AD models.

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Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer’s disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis

Cited by 111 publications

References 42 publications

Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease

Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease

Mesenchymal stem cells: Cell therapy and regeneration potential

HGF Mediates Clinical‐Grade Human Umbilical Cord‐Derived Mesenchymal Stem Cells Improved Functional Recovery in a Senescence‐Accelerated Mouse Model of Alzheimer's Disease

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