# Beyond Molecular Markers: The Therapeutic Significance of Mesenchymal Stem Cell Deformability in Regenerative Medicine

## TL;DR

This paper shows that the ability of mesenchymal stem cells to deform is a key indicator of their quality and effectiveness for regenerative therapies.

## Contribution

Introduces cellular deformability as a novel, functional biomarker for assessing mesenchymal stem cell quality and therapeutic potential.

## Key findings

- Cellular deformability correlates with stemness, homing efficiency, and differentiation status of MSCs.
- Real-time deformability cytometry and AI-based imaging are practical tools for assessing MSC mechanotype.
- Incorporating deformability into quality control can improve clinical outcomes by enriching potent MSC subpopulations.

## Abstract

What are the main findings?
Cellular deformability is an integrative, functional biomarker of MSC quality, correlated with stemness, homing efficiency, early differentiation, and aging status.Real-time deformability cytometry (RT-DC) and emerging AI-based imaging predictors represent the most translatable tools for mechanotype assessment. A practical GMP-oriented framework is proposed.

Cellular deformability is an integrative, functional biomarker of MSC quality, correlated with stemness, homing efficiency, early differentiation, and aging status.

Real-time deformability cytometry (RT-DC) and emerging AI-based imaging predictors represent the most translatable tools for mechanotype assessment. A practical GMP-oriented framework is proposed.

What is the implications of the main findings?
Incorporating deformability into ATMP quality control and sorting can enrich preparations with therapeutically potent MSC subpopulations, reduce heterogeneity, and improve clinical outcomes.Standardized protocols and validation, combined with multi-omics integration, can enable personalized, mechanotype-guided manufacturing of MSC therapies.

Incorporating deformability into ATMP quality control and sorting can enrich preparations with therapeutically potent MSC subpopulations, reduce heterogeneity, and improve clinical outcomes.

Standardized protocols and validation, combined with multi-omics integration, can enable personalized, mechanotype-guided manufacturing of MSC therapies.

Mesenchymal stem cells (MSCs) are characterized by their unique therapeutic properties, which include the ability to differentiate, secrete paracrine factors, and migrate toward sites of tissue injury. Although classical molecular markers facilitate phenotypic characterization, they do not always reflect the true functional capacity of MSCs. This article introduces deformability, i.e., the capacity of cells to deform under mechanical forces, as a novel, integrative marker of MSC biological quality. It examines the relationship between cellular mechanical deformability and key therapeutic attributes, such as stemness, homing ability, and differentiation status. It overviews current measurement techniques, categorized by resolution, throughput, and clinical applicability. The potential applications of deformability in quality control and cell sorting for therapeutic purposes are also discussed. The article proposes that, in addition to molecular features, deformability may serve as a functional biomarker, potentially enhancing the effectiveness of MSC-based therapies.