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Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine.

ABSTRACT: Extracellular vesicles (EVs), which are the main paracrine components of stem cells, mimic the regenerative capacity of these cells. Stem cell-derived EVs (SC-EVs) have been used for the treatment of various forms of tissue injury in preclinical trials through maintenance of their stemness, induction of regenerative phenotypes, apoptosis inhibition, and immune regulation. The efficiency of SC-EVs may be enhanced by selecting the appropriate EV-producing cells and cell phenotypes, optimizing cell culture conditions for the production of optimal EVs, and further engineering the EVs produced to transport therapeutic and targeting molecules.

SUBMITTER: Yin L

PROVIDER: S-EPMC7140663 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine.

Yin Lei L Liu Xiaotian X Shi Yinghong Y Ocansey Dickson Kofi Wiredu DKW Hu Yuyan Y Li Xiaoxi X Zhang Chenxiao C Xu Wenrong W Qian Hui H

Cells 20200313 3

Extracellular vesicles (EVs), which are the main paracrine components of stem cells, mimic the regenerative capacity of these cells. Stem cell-derived EVs (SC-EVs) have been used for the treatment of various forms of tissue injury in preclinical trials through maintenance of their stemness, induction of regenerative phenotypes, apoptosis inhibition, and immune regulation. The efficiency of SC-EVs may be enhanced by selecting the appropriate EV-producing cells and cell phenotypes, optimizing cell ...[more]

PMID: 32183102

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Project description:Abdominal aortic aneurysms (AAA) are localized expansions of the abdominal aorta that develop due to chronic proteolytic disruption of the structural extracellular matrix (ECM) components (elastin and collagen) within the aorta wall. Major limitations in arresting or reversing AAAs lie in naturally poor and aberrant regeneration and repair of elastic matrix structures in the aorta wall. Bone marrow derived mesenchymal stem cells (BM-MSCs) have emerged as a promising regenerative tool and their therapeutic effects are also known to be effected through their paracrine secretions. Extracellular vesicles (EVs) present in these secretions have emerged as critical cellular component in facilitating many therapeutic benefits of MSCs. EV treatment is thus potentially appealing as a stem cell-inspired cell-free approach to avoid possible phenotypic plasticity of MSCs in vivo. In this study, we investigated the thus far unknown effects of BM-MSC derived EVs on vascular elastic matrix repair in the context of AAA treatment. EVs isolated from BM-MSC source were characterized and their pro-regenerative and their anti-proteolytic effects were evaluated on our established in vitro experimental conditions derived from AAA rat model. Our studies revealed the efficacy of BM-MSC derived EVs in attenuating the proteolytic activity and also in imparting elastic matrix regenerative benefits under aneurysmal environment. Interestingly, compared to cell culture conditioned media (CCM), EVs demonstrated superior regenerative and anti-proteolytic benefits in a proteolytic injury culture model of AAA. From these studies, it appears that EVs derived from BM-MSCs could be beneficial in undertaking a reparative effort in AAA induced degeneration of vascular tissue. Statement of Significance Abdominal aortic aneurysms (AAAs) are localized, rupture-prone expansions of the aorta which result from loss of wall flexibility due to enzymatic breakdown of elastic fibers. There are no established alternatives to surgery, which possess high risk for the mostly elderly patients. Our previous studies have established the elastic regenerative and reparative effect of cell culture secretions derived from adult stem cell source. In this study, we propose to isolate extracellular vesicles (exosomes) from these secretions and evaluate their regenerative benefits in AAA smooth muscle cell culture model. This simple and innovative treatment approach has the potential to arrest or reverse AAA growth to rupture, not possible so far.

Project description:The cells secrete extracellular vesicles (EV) that may have an endosomal origin, or from evaginations of the plasma membrane. The former are usually called exosomes, with sizes ranging from 50 to 100 nm. These EV contain a lipid bilayer associated to membrane proteins. Molecules such as nucleic acids (DNA, mRNA, miRNA, lncRNA, etc.) and proteins may be stored inside. The EV composition depends on the producer cell type and its physiological conditions. Through them, the cells modify their microenvironment and the behavior of neighboring cells. That is accomplished by transferring factors that modulate different metabolic and signaling pathways. Due to their properties, EV can be applied as a diagnostic and therapeutic tool in medicine. The mesenchymal stromal cells (MSC) have immunomodulatory properties and a high regenerative capacity. These features are linked to their paracrine activity and EV secretion. Therefore, research on exosomes produced by MSC has been intensified for use in cell-free regenerative medicine. In this area, the use of EV for the treatment of chronic skin ulcers (CSU) has been proposed. Such sores occur when normal healing does not resolve properly. That is usually due to excessive prolongation of the inflammatory phase. These ulcers are associated with aging and diseases, such as diabetes, so their prevalence is increasing with the one of such latter disease, mainly in developed countries. This has very important socio-economic repercussions. In this review, we show that the application of MSC-derived EV for the treatment of CSU has positive effects, including accelerating healing and decreasing scar formation. This is because the EV have immunosuppressive and immunomodulatory properties. Likewise, they have the ability to activate the angiogenesis, proliferation, migration, and differentiation of the main cell types involved in skin regeneration. They include endothelial cells, fibroblasts, and keratinocytes. Most of the studies carried out so far are preclinical. Therefore, there is a need to advance more in the knowledge about the conditions of production, isolation, and action mechanisms of EV. Interestingly, their potential application in the treatment of CSU opens the door for the design of new highly effective therapeutic strategies.

Dataset Information

Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine.

Publications

Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine.

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