Macrophage migration inhibitory factor rejuvenates aged human mesenchymal stem cells and improves myocardial repair

Ding

et al. 2020

Front. Cell Dev. Biol.

Self Cite

186

136

Mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and differentiation. There is increasing evidence of the therapeutic value of MSCs in various clinical situations, however, these cells gradually lose their regenerative potential with age, with a concomitant increase in cellular dysfunction. Stem cell aging and replicative exhaustion are considered as hallmarks of aging and functional attrition in organisms. MSCs do not proliferate infinitely but undergo only a limited number of population doublings before becoming senescent. This greatly hinders their clinical application, given that cultures must be expanded to obtain a sufficient number of cells for cellbased therapy. Here, we review the current knowledge of the phenotypic and functional characteristics of senescent MSCs, molecular mechanisms underlying MSCs aging, and strategies to rejuvenate senescent MSCs, which can broaden their range of therapeutic applications.

Section: Strategies For Rejuvenating Senescent Mscsmentioning

confidence: 99%

Senescence in Mesenchymal Stem Cells: Functional Alterations, Molecular Mechanisms, and Rejuvenation Strategies

Ding

et al. 2020

Front. Cell Dev. Biol.

Self Cite

186

136

“…In addition, in vitro amplification of MSCs is necessary prior to their clinical application and inevitably leads to replicative aging process (Mathiasen et al, 2015;Guijarro et al, 2016). Accumulating evidence shows that aging affects the functions of MSCs, including differentiation, proliferation and migration, as well as angiogenic potential, and in turn reduces their clinical efficacy (Malaise et al, 2019;Zhang et al, 2019;Wang et al, 2020). There is an urgent need to explore strategies that will enable functional recovery of elderly MSCs.…”

Section: Introductionmentioning

confidence: 99%

Down-Regulated Exosomal MicroRNA-221 – 3p Derived From Senescent Mesenchymal Stem Cells Impairs Heart Repair

Sun

Zhu

Zhao

et al. 2020

Front. Cell Dev. Biol.

Self Cite

The composition and biological activity of donor cells is largely determined by the exosomes they secrete. In this study, we isolated exosomes from young (Young-Exo) and aged (Age-Exo) mesenchymal stem cells (MSCs) and compared their regeneration activity. Young Exo MSCs were more efficient than Aged-Exo at promoting the formation of endothelial tube, reducing fibrosis, and inhibiting apoptosis of cardiomyocytes in vitro; and improving cardiac structure and function in vivo in the hearts of rats following myocardial infarction (MI). MicroRNA sequencing and polymerase chain reaction (PCR) analysis revealed that miR-221-3p was significantly down-regulated in Aged-Exo. The aged MSCs were rejuvenated and their reparative cardiac ability restored when miR-221-3p was overexpressed in Aged-Exo. The protective effect was lost when miR-221-3p expression was knocked down in Young-Exo. These effects of miR-221-3p were achieved through enhancing Akt kinase activity by inhibiting phosphatase and tensin homolog (PTEN). In conclusion, exosomal miR-221-3p secreted from Aged MSCs attenuated the function of angiogenesis and promoted survival of cardiomyocytes. Upregulation of miR-221-3p in aged MSCs improved their ability of angiogenesis, migration and proliferation, and suppressed apoptosis via the PTEN/Akt pathway.

“…In recent years, mesenchymal stem cells (MSCs) have been widely used in clinical treatment owing to their multi-differentiation potential [1,2]. These cells play a signi cant role in immune regulation [3] and angiogenesis [4], especially in the heart, bone, cartilage, nerves and skin [5][6][7]. There are many tissuederived MSCs that have been used in therapeutic research, such as bone marrow (BM), adipose tissue (AT), fetal lung, dental pulp, and umbilical cord (UC) [8,9].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Proteomic Analysis of Exosomes Derived from Human Bone Marrow-, Adipose Tissue-, and Umbilical Cord- Mesenchymal Stem Cells

Wang

Liang

et al. 2020

Preprint

Background: Mesenchymal stem cells (MSCs)-derived exosomes have shown comprehensive application prospects over the years. Despite performing similar functions, exosomes from different origins present heterogeneous characteristics and components; however, relative study remains scarce. Lacking of a valuable reference, researchers select source cells for exosome studies mainly based on accessibility and personal preference.Methods: In this study, exosomes secreted by MSCs derived from different tissues were isolated, by ultracentrifugation, and proteomics analysis was performed. A total of 1,014 proteins were detected using a label-free method. Results: Bioinformatics analysis revealed their shared function in the extracellular matrix receptor. Bone marrow-MSCs-derived exosomes showed superior regeneration ability, and adipose tissue-MSCs-derived exosomes played a significant role in immune regulation, whereas, umbilical cord-MSCs-derived exosomes were more prominent in tissue damage repair.Conclusions: This study systematically and comprehensively analyzes the human MSCs-derived exosomes via proteomics, which reveals their potential applications in different fields, so as to provide a reference for researchers to select optimal source cells in future exosome-related studies.