Mesenchymal stem/stromal cells as a delivery platform in cell and gene therapies

Abstract

Regenerative medicine relying on cell and gene therapies is one of the most promising approaches to repair tissues. Multipotent mesenchymal stem/stromal cells (MSC), a population of progenitors committing into mesoderm lineages, are progressively demonstrating therapeutic capabilities far beyond their differentiation capacities. The mechanisms by which MSC exert these actions include the release of biomolecules with anti-inflammatory, immunomodulating, anti-fibrogenic, and trophic functions. While we expect the spectra of these molecules with a therapeutic profile to progressively expand, several human pathological conditions have begun to benefit from these biomolecule-delivering properties. In addition, MSC have also been proposed to vehicle genes capable of further empowering these functions. This review deals with the therapeutic properties of MSC, focusing on their ability to secrete naturally produced or gene-induced factors that can be used in the treatment of kidney, lung, heart, liver, pancreas, nervous system, and skeletal diseases. We specifically focus on the different modalities by which MSC can exert these functions. We aim to provide an updated understanding of these paracrine mechanisms as a prerequisite to broadening the therapeutic potential and clinical impact of MSC.

Fig. 1

MSC paracrine action/mechanisms in heart regeneration. Soluble factors released by MSC play an essential role in the post-ischemic reparative process improving angiogenesis, cytoprotection, and endogenous cardiac regeneration and reducing fibrosis. Ang-1 angiopoietin 1, HGF hepatocyte growth factor, MSC mesenchymal stem/stromal cells, VEGF vascular endothelial growth factor

Fig. 2

MSC immunomodulatory properties in pancreatic regeneration. MSC are able to modulate the autoimmune response in T1D either by inducing regulatory T cells or by shifting the cytokine profile from a pro-inflammatory to an anti-inflammatory one. APC Antigen Presenting Cell, CTL Cytotoxic T Lymphocyte, Th1/2 T helper cell type 1/2, Treg regulatory T cell

Fig. 3

The therapeutic potential of MSC microvesicles in kidney regeneration. MSC MV mediate anti-apoptotic and pro-proliferative effects, simultaneously reducing oxidative stress to stimulate renal regeneration after acute kidney injury