Abstract
Mesenchymal stem cells (MSCs) are multipotent cells with regenerative and immunomodulatory properties. Several aspects of MSC function have been attributed to the paracrine effects of MSC derived extracellular vesicles (EVs). Although MSC EVs show great promise for regenerative medicine applications, insights into their uptake mechanisms by different target cells and the ability to control MSC EV properties for defined function in vivo have remained elusive knowledge gaps. The primary goal of this study is to elucidate how the basic properties of MSC derived EVs can be exploited for function-specific activity in regenerative medicine. Our first important observation is that, MSC EVs possess a common mechanism of endocytosis across multiple cell types. Second, altering the MSC state by inducing differentiation into multiple lineages did not affect the exosomal properties or endocytosis but triggered the expression of lineage-specific genes and proteins in vitro and in vivo respectively. Overall, the results presented in this study show a common mechanism of endocytosis for MSC EVs across different cell types and the feasibility to generate functionally enhanced EVs by modifications to parental MSCs.
Highlights
Human mesenchymal stem cells (HMSCs) are multipotent somatic stem cells that can be isolated from a variety of tissues such as the bone marrow, adipose tissue, and dental pulp
Immunoblot analysis indicated the presence of exosomal marker proteins CD63 (Figure 1D) and CD9 (Figure 1E) in both naïve and differentiated HMSC Extracellular vesicles (EVs), but not in the EV depleted conditioned medium
HMSC EVs are of current interest because they demonstrate immunomodulatory and regenerative potential that may rival the use of HMSCs or growth factors in regenerative medicine (Cheng et al, 2017)
Summary
Human mesenchymal stem cells (HMSCs) are multipotent somatic stem cells that can be isolated from a variety of tissues such as the bone marrow, adipose tissue, and dental pulp. As of 2016, about 493 clinical trials that used HMSCs were reported in the National Institutes of Health (NIH) clinical trials database (Squillaro et al, 2016). Issues such as donor dependent variability, cellular viability, poor attachment, and aberrant differentiation. The single morphogen system shows initial promise, when applied clinically, issues such as dosage, specificity, ectopic effects, toxicity, and immunological complications have posed significant restrictions to clinical efficiency as well as translational potential (Soltani et al, 2015). Extracellular vesicles (EVs)/exosomes can satisfy these criteria (Marcus and Leonard, 2013)
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