MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model

Abstract

Widespread death of transplanted mesenchymal stem cells (MSCs) hampers the development of stem cell therapy for Alzheimer disease (AD). Cell pre-conditioning might help cope with this challenge. We tested whether let-7f-5p-modified MSCs could prolong the survival of MSCs after transplantation. When exposed to Aβ25−35 in vitro, MSCs showed significant early apoptosis with decrease in the let-7f-5p levels and increased caspase-3 expression. Upregulating microRNA let-7f-5p in MSCs alleviated Aβ25−35-induced apoptosis by decreasing the caspase-3 levels. After computerized analysis and the luciferase reporter assay, we identified that caspases-3 was the target gene of let-7f-5p. In vivo, hematoxylin and eosin staining confirmed the success of MSCs transplantation into the lateral ventricles, and the let-7f-5p upregulation group showed the lowest apoptotic rate of MSCs detected by TUNEL immunohistochemistry analysis and immunofluorescence. Similarly, bioluminescent imaging showed that let-7f-5p upregulation moderately prolonged the retention of MSCs in brain. In summary, we identified the anti-apoptotic role of let-7f-5p in Aβ25−35-induced cytotoxicity, as well as the protective effect of let-7f-5p on survival of grafted MSCs by targeting caspase-3 in AD models. These findings show a promising approach of microRNA-modified MSCs transplantation as a therapy for neurodegenerative diseases.

MicroRNA Let-7i Is a Promising Serum Biomarker for Post-stroke Cognitive Impairment and Alleviated OGD-Induced Cell Damage in vitro by Regulating Bcl-2

“…Similarly, it was also reported to attenuate endothelial cell damage in the OGD model, which further supported our results (Xiang et al, 2017). Besides, multiple evidences have proved that miRNAs, such as miR-203, let-7, miR-195, and miR-122, all exert the anti-apoptotic effect to protect against cell injury (Yang et al, 2015;Guo et al, 2018;Han et al, 2018;Cheng et al, 2019). Thus, miRNAs have the potential to become the novel therapeutic target for nervous system disease.…”

Mesenchymal stem cells: Cell therapy and regeneration potential

“…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, ).…”

“…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.…”

“…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.…”

“…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.…”