Anti-fibrotic mechanisms of exogenously-expanded mesenchymal stromal cells for fibrotic diseases

Jason S Rockel; Razieh Rabani; Sowmya Viswanathan

doi:10.1016/j.semcdb.2019.10.014

Anti-fibrotic mechanisms of exogenously-expanded mesenchymal stromal cells for fibrotic diseases

Semin Cell Dev Biol. 2020 May:101:87-103. doi: 10.1016/j.semcdb.2019.10.014. Epub 2019 Nov 19.

Authors

Jason S Rockel¹, Razieh Rabani², Sowmya Viswanathan³

Affiliations

¹ Arthritis Program, University Health Network, Toronto, ON, Canada; Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON, Canada. Electronic address: jason.rockel@utoronto.ca.
² Arthritis Program, University Health Network, Toronto, ON, Canada; Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON, Canada.
³ Arthritis Program, University Health Network, Toronto, ON, Canada; Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada; Division of Hematology, Department of Medicine, University of Toronto, Toronto, Canada.

PMID: 31757583
DOI: 10.1016/j.semcdb.2019.10.014

Abstract

Most chronic diseases involving inflammation have a fibrotic component that involves remodeling and excess accumulation of extracellular matrix components. Left unchecked, fibrosis leads to organ failure and death. Mesenchymal stromal cells (MSCs) are emerging as a potent cell-based therapy for a wide spectrum of fibrotic conditions due to their immunomodulatory, anti-inflammatory and anti-fibrotic properties. This review provides an overview of known mechanisms by which MSCs mediate their anti-fibrotic actions and in relation to animal models of pulmonary, liver, renal and cardiac fibrosis. Recent MSC clinical trials results in liver, lung, skin, kidney and hearts are discussed and next steps for future MSC-based therapies including pre-activated or genetically-modified cells, or extracellular vesicles are also considered.

Keywords: Anti-fibrotic mechanisms of action; Clinical trials; Fibrosis; Heterogeneity; Mesenchymal stromal cells; Pre-clinical animal models.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antifibrinolytic Agents / pharmacology*
Fibrosis / drug therapy*
Fibrosis / pathology
Humans
Mesenchymal Stem Cells / drug effects*
Mesenchymal Stem Cells / pathology

Substances

Antifibrinolytic Agents