# Ex Vivo Preconditioning as a Useful Tool for Modification of the Extracellular Matrix of Multipotent Mesenchymal Stromal Cells

## TL;DR

This review discusses how preconditioning mesenchymal stem cells can modify their extracellular matrix, enhancing their use in regenerative medicine.

## Contribution

The paper highlights the underappreciated impact of preconditioning on extracellular matrix modification for therapeutic applications.

## Key findings

- Preconditioning methods like hypoxia and 3D culture stimulate extracellular matrix production and stiffness.
- Modified extracellular matrix supports angiogenesis and lineage differentiation in regenerative therapies.

## Abstract

Cell technologies have provided promising tools for modulating the properties of multipotent mesenchymal stem/stromal cells (MSCs) to meet the needs of cell therapy as well as tissue engineering and regenerative medicine (TERM). Ex vivo preconditioning is directed at enhancing the engraftment of MSCs and activating their secretory activity, primarily the production of soluble mediators. The present review aims to highlight the underestimated effect of the most accepted preconditioning approaches on the modification of the important set of insoluble molecules secreted by MSCs into extracellular space—the extracellular matrix (ECM). A thorough review of the published literature was performed, with particular emphasis on ECM-related data. The analysis of data on ECM changes showed that most of the applied preconditioning methods—hypoxia, inflammatory priming, pharmacological agents, 3D culture, and scaffolds—generally stimulate ECM production, increase the deposition of growth factors, promote alignment, and increase ECM stiffness. There are already preliminary results demonstrating the successful application of preconditioned ECM for promoting angiogenesis, targeted stromal lineage differentiation, and other therapeutic goals. The prospects for further research in this area are discussed.