Osteoarthritis Bone Marrow MSCs Retain Regenerative Competence and Chemokine Responsiveness for Drug-Based In Situ Tissue Engineering

Sep 29, 2026

Uploaded by jayni

Osteoarthritis requires improved repair strategies beyond symptomatic care, and mesenchymal stromal cells (MSCs) are promising for in situ tissue engineering via directed migration to damaged sites. This study compared MSCs from non-OA and OA donors, assessing differentiation capacity, senescence status, chemokine receptor expression, and functional responses. Findings showed no OA-related reduction in regenerative potency, no increased senescent phenotype, and preserved responsiveness to the chemoattractant CCL25, supporting targeted in situ repair potential.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Introduction

Methods and Results

MSC characterization: differentiation and senescence

Chemokine receptor profiling

Migration and CCL25-driven functional effects

Genome-wide pathway analyses

Conclusion

Wiley Stem Cells International Volume 2025, Article ID 3757831, 26 pages [https://doi.org/10.1155/sci/3757831](https://doi.org/10.1155/sci/3757831) Research Article Osteoarthritis Bone Marrow MSCs Retain Regenerative Competence and Chemokine Responsiveness for Drug-Based In Situ Tissue Engineering Julia Sonnleitner, 1 Katja Gulich, 1 Axel Pruss,2 Carsten Perka ,3 Angelika Gursche,4 Daniel Kendoff,4 Michael Sittinger, 1 Shabnam Hemmati-Sadeghi , 1 and Tilo Dehne 1 1 Tissue Engineering Laboratory, Department for Rheumatology and Clinical Immunology, Charité–Universitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany 2Institute of Transfusion Medicine, University Tissue Bank, Charité–Universitätsmedizin Berlin, Berlin 10117, Germany 3Center for Musculoskeletal Surgery, Charité–Universitätsmedizin Berlin, Berlin 10117, Germany 4Department of Orthopaedic Surgery, Helios Klinikum Berlin-Buch, Berlin 13125, Germany Correspondence should be addressed to Shabnam Hemmati-Sadeghi; shabnam.hemmati-sadeghi@charite.de Shabnam Hemmati-Sadeghi and Tilo Dehne contributed equally to this work. Received 22 May 2025; Revised 11 November 2025; Accepted 26 November 2025 Academic Editor: Yuriy Petrenko Copyright © 2025 Julia Sonnleitner et al. Stem Cells International published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Background: Mesenchymal stromal cells (MSCs) support tissue repair in osteoarthritis (OA), with migration to damaged tissue being a key strategy in in situ tissue engineering. Their regenerative potential depends on factors such as differentiation, level of senescence, and responsiveness to signaling molecules. However, previous ﬁndings on these properties of OA MSCs remain inconclusive. This study integrates multiple aspects and tests feasibility using a well-characterized chemoattractant. Methods and Results: MSCs from non-OA donor (ND) and OA donor were characterized for their trilineage differentiation potential as well as for their senescence level by (immune-) histochemistry, RT-qPCR, microarray analysis, and a bead-based immunoassay for cell culture supernatants. No difference in differentiation and senescence level was observed, the latter being indicated by a similar activity of β-Galactosidase (β-gal), gene expression proﬁles of cyclin-dependent kinase (CDKN) inhibitor 2A (CDKN2A), CDKN inhibitor 1A (CDKN1A), sirtuin 1 (SIRT1), and matrix metallopeptidase 1 (MMP1), as well as secreted cytokines. Chemokine receptors in OA MSCs were detected using immunohistochemistry and RT-qPCR. Expression of CCR1-CCR7, CCR9, and CXCR1-CXCR6 in OA MSCs was conﬁrmed on gene and protein levels. Both OA and ND MSCs migrated toward 1000nM CCL25, as evaluated via a Boyden chamber assay. Subsequent genome-wide microarray analysis ofOA MSCs after treatment with 1000nM CCL25 corroborated its inﬂuence on migration, proliferation, apoptosis, and differentiation as deﬁned by Gene Ontology terms (GO terms) . Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis conﬁrmed this broad impact and emphasized the role of cytokine–cytokine–receptor interaction and metabolic pathways. Conclusion: Our data indicate that OA MSCs retain their differentiation potential and do not exhibit an increased senescent phenotype. Their chemokine receptor proﬁle is conducive of migration, and both OA and ND MSCs respond to CCL25, highlighting the potential of OA MSCs for directed in situ repair. 1. Introduction Osteoarthritis (OA) is a chronic, multifactorial disease of the joint, which involves synovial inﬂammation, bone remodeling, and cartilage destruction [1] . It poses a serious burden of global disease, with an incidence rate that has increased by 9.3% between 1990 and 2017 [2] . The prevalence of knee OAin people older than 40 years

FAQs

How did the study assess MSC regenerative competence in osteoarthritis?

It characterized MSCs from non-OA and OA donors for trilineage differentiation potential and senescence level using (immune-)histochemistry, RT-qPCR, microarray analysis, and bead-based immunoassays for culture supernatants.

Did osteoarthritis MSCs show increased senescence or reduced differentiation?

No. The results indicated no difference in differentiation and no OA-associated increased senescent phenotype, reflected by similar β-gal activity, senescence-related gene expression profiles, and secreted cytokine patterns.

What role did CCL25 play in MSC behavior?

OA and non-OA MSCs migrated toward 1000 nM CCL25 in a Boyden chamber assay. Genome-wide analyses after CCL25 treatment supported its influence on migration, proliferation, apoptosis, and differentiation-related pathways.

Sep 29, 2026

Uploaded by jayni