Enhancement of the efficacy of mesenchymal stem cells in the treatment of ischemic diseases

Luo, Ruixi; Liu, Yanrong; Liu, Jingping; Cheng, Jun; Chen, Younan

doi:10.1016/j.biopha.2018.11.068

Cited by 31 publications

(24 citation statements)

References 158 publications

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“…A growing number of clinical studies have demonstrated the usefulness of stem/progenitor cell transplantation for various diseases. 19 , 20 , 21 , 22 , 23 There are still many challenges facing the use of this emerging cell therapy. 53 In our study, we used systemic injection of hMSCs and developed a new method using gLuc-fusion MFG-E8 to monitor the amount of exosome produced by the injected MSCs.…”

Section: Discussionmentioning

confidence: 99%

“… 17 , 18 A gain in MSCs is beneficial in a variety of diseases, including graft-versus-host disease, 19 heart disease, 20 type 1 diabetes, 21 and type 2 diabetes. 22 According to the public clinical trials database, 23 more than 893 clinical trials have, so far, used MSCs in the treatment of diverse diseases. However, there is limited knowledge on the alteration of its efficacy by factors in recipients.…”

Section: Introductionmentioning

confidence: 99%

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Adiponectin Stimulates Exosome Release to Enhance Mesenchymal Stem-Cell-Driven Therapy of Heart Failure in Mice

et al. 2020

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Mesenchymal stem/stromal cells (MSCs) are cultured adult stem cells that originally reside in virtually all tissues, and the gain of MSCs by transplantation has become the leading form of cell therapy in various diseases. However, there is limited knowledge on the alteration of its efficacy by factors in recipients. Here, we report that the cardioprotective properties of intravenously injected MSCs in a mouse model of pressure-overload heart failure largely depend on circulating adiponectin, an adipocyte-secreted factor. The injected MSCs exert their function through exosomes, extracellular vesicles of endosome origin. Adiponectin stimulated exosome biogenesis and secretion through binding to T-cadherin, a unique glycosylphosphatidylinositol-anchored cadherin, on MSCs. A pharmacological or adenovirus-mediated genetic increase in plasma adiponectin enhanced the therapeutic efficacy of MSCs. Our findings provide novel insights into the importance of adiponectin in mesenchymal-progenitor-mediated organ protections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adiponectin Stimulates Exosome Release to Enhance Mesenchymal Stem-Cell-Driven Therapy of Heart Failure in Mice

et al. 2020

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“…In particular, mesenchymal stem cells (MSCs) have been commonly used in the animal models and clinical trials for two decades, and shown a promise in the treatment of numerous diseases, mainly tissue injury and immune disorders [11]. Moreover, intensive studies have been conducted to demonstrate that due to their capacity of secreting multiple angiogenic and growth factors, MSCs have a great potential in the repair of damaged vascular and parenchymal cells, benefiting tissue regeneration and function recovery of ischemia diseases [12]. MSCs can be derived from several tissues including the umbilical cord blood, adipose tissue, and bone marrow.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model

et al. 2020

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Background: Diabetic cystopathy (DCP) is a chronic complication of diabetes mainly within the submucosal and muscular layers of the bladder due to the hyperglycemia-induced ischemia. As no effective therapies are currently available, the administration of optimized mesenchymal stem cells (MSCs) provides a potential treatment of DCP. Thus far, new strategy, such as genetic modification of MSCs, has been developed and has shown promising outcomes of various disorders. Methods: This study was conducted using integrin-linked kinase (ILK) gene-modified bone marrow-derived stem cells (BMSCs) for streptozotocin (STZ)-induced diabetic cystopathy in a rat model. In total, 68 male Sprague-Dawley rats were randomized into five groups: sham control (control group, n = 10); DCP model alone (DM group, n = 10); DCP rats intravenously treated with BMSCs (BMSC group, n = 16); DCP rats accepted adenoviral vector-infected BMSCs (Ad-null-BMSC group, n = 16) and DCP rats accepted ILK adenoviral vector-infected BMSCs (Ad-ILK-BMSC group, n = 16). Diabetic rats accepted cell transplantation in the experimental group (2 rats per group) were sacrificed for the bladder tissue on the third day, 7th day, and 14th day of treatment respectively ahead of schedule. At 4 weeks after treatment, all rats in five groups accepted urodynamic studies to evaluate bladder function and were sacrificed for bladder tissue. Results: Our data showed that the underactive bladder function was significantly improved in DCP rats intravenously treated with ILK gene-modified BMSCs compared to those in the DM, BMSCs, and Ad-null-BMSC group. Meanwhile, we found that gene-modified BMSC treatment significantly promoted the activation of the AKT/ GSK-3β pathway by increasing phosphorylation and led to the enhancement of survival. In addition, the expression levels of angiogenesis-related protein vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1 (SDF-1) were significantly higher in the Ad-ILK-BMSC group than that in the DM, BMSCs, and Ad-null-BMSC group as assessed by enzyme-linked immunosorbent assay and western blot. As two indicators of vascular endothelial cell markers, the expression of von Willebrand factor (vWF) and CD31 by

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“…Initially, it was proposed the differentiation of transplanted MSC into cardiomyocytes and vessels as the main mechanism underlying their therapeutic action in cardiovascular diseases (Tomita et al, 1999;Pittenger and Martin, 2004). However, the number of MSCs-derived cells has been shown to be too low to contribute to the functional improvements, and evidence supports the hypothesis that MSC-mediated paracrine mechanisms play an essential role in tissue repair (Luo et al, 2019). Among the mechanisms promoted by MSCs are neovascularization, cytoprotection, endogenous cardiac regeneration, modulation of inflammatory and fibrogenic processes, cardiac contractility and cardiac metabolism (Gnecchi and Cervio, 2013).…”

Section: Applications In Cardiovascular Diseasesmentioning

confidence: 99%

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine

Damasceno

Santana

Santos

et al. 2020

Front. Cell Dev. Biol.

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Mesenchymal stem/stromal cells (MSCs) have been widely studied in the field of regenerative medicine for applications in the treatment of several disease settings. The therapeutic potential of MSCs has been evaluated in studies in vitro and in vivo, especially based on their anti-inflammatory and pro-regenerative action, through the secretion of soluble mediators. In many cases, however, insufficient engraftment and limited beneficial effects of MSCs indicate the need of approaches to enhance their survival, migration and therapeutic potential. Genetic engineering emerges as a means to induce the expression of different proteins and soluble factors with a wide range of applications, such as growth factors, cytokines, chemokines, transcription factors, enzymes and microRNAs. Distinct strategies have been applied to induce genetic modifications with the goal to enhance the potential of MCSs. This review aims to contribute to the update of the different genetically engineered tools employed for MSCs modification, as well as the factors investigated in different fields in which genetically engineered MSCs have been tested.

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Enhancement of the efficacy of mesenchymal stem cells in the treatment of ischemic diseases

Cited by 31 publications

References 158 publications

Adiponectin Stimulates Exosome Release to Enhance Mesenchymal Stem-Cell-Driven Therapy of Heart Failure in Mice

Adiponectin Stimulates Exosome Release to Enhance Mesenchymal Stem-Cell-Driven Therapy of Heart Failure in Mice

Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine

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