Mesenchymal Stromal Cell Secretome: Influencing Therapeutic Potential by Cellular Pre-conditioning.

Joana R Ferreira,Mário A Barbosa,Raquel M Gonçalves,Graciosa Q Teixeira,Susana G Santos,Graça Almeida-Porada

doi:10.3389/fimmu.2018.02837

Abstract

Mesenchymal stromal cells (MSCs) are self-renewing, culture-expandable adult stem cells that have been isolated from a variety of tissues, and possess multipotent differentiation capacity, immunomodulatory properties, and are relatively non-immunogenic. Due to this unique set of characteristics, these cells have attracted great interest in the field of regenerative medicine and have been shown to possess pronounced therapeutic potential in many different pathologies. MSCs' mode of action involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. For this reason, MSCs' secretome is currently being explored in several clinical contexts, either using MSC-conditioned media (CM) or purified MSC-derived extracellular vesicles (EVs) to modulate tissue response to a wide array of injuries. Rather than being a constant mixture of molecular factors, MSCs' secretome is known to be dependent on the diverse stimuli present in the microenvironment that MSCs encounter. As such, the composition of the MSCs' secretome can be modulated by preconditioning the MSCs during in vitro culture. This manuscript reviews the existent literature on how preconditioning of MSCs affects the therapeutic potential of their secretome, focusing on MSCs' immunomodulatory and regenerative features, thereby providing new insights for the therapeutic use of MSCs' secretome.

Highlights

Mesenchymal stromal cells (MSCs), defined by the International Society for Stem Cell Research (ISSCR) as fibroblast-like non-hematopoietic cells, have been explored in recent years due to the clinical promise they hold for tissue repair in regenerative medicine [1, 2]
MSCs-derived extracellular vesicles (EVs) obtained after preconditioning with Buyang Huanwu Decoction (BYHWD), a drug that has been used for centuries for the treatment of paralysis and stroke, was shown to attenuate brain injury in a rat local cerebral ischemia model by increasing local VEGF levels [146]
Extensive evidence exists to support the benefits of preconditioning of MSCs with respect to improving their capacity to induce regeneration/repair across the wide array of tissues and pathologic conditions in which these cells have been explored

Summary

Introduction

Mesenchymal stromal cells (MSCs), defined by the International Society for Stem Cell Research (ISSCR) as fibroblast-like non-hematopoietic cells, have been explored in recent years due to the clinical promise they hold for tissue repair in regenerative medicine [1, 2]. When using hypoxia-preconditioned MSCs-derived EVs to treat acute myocardial infarction, authors reported the importance of the increased vascularization in the therapeutic effects.

Results

Conclusion