TWIST1 and TSG6 are coordinately regulated and function as potency biomarkers in human MSCs

• Published in: Science advances Vol. 9; no. 45; p. eadi2387
• Main Authors: Lee, Ryang Hwa, Boregowda, Siddaraju V, Shigemoto-Kuroda, Taeko, Bae, EunHye, Haga, Christopher L, Abbery, Colette A, Bayless, Kayla J, Haskell, Andrew, Gregory, Carl A, Ortiz, Luis A, Phinney, Donald G
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 10.11.2023
• Subjects: Anti-Inflammatory Agents - pharmacology; Biomarkers - metabolism; Biomedicine and Life Sciences; Bone Marrow Cells - metabolism; Cell Differentiation; Humans; Immunologic Factors - metabolism; Immunology; Mesenchymal Stem Cells - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; SciAdv r-articles; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.adi2387

Mesenchymal stem/stromal cells (MSCs) have been evaluated in >1500 clinical trials, but outcomes remain suboptimal because of knowledge gaps in quality attributes that confer potency. We show that TWIST1 directly represses expression that and are inversely correlated across bone marrow-derived MSC (BM-MSC) donor cohorts and predict interdonor differences in their proangiogenic, anti-inflammatory, and immune suppressive activity in vitro and in sterile inflammation and autoimmune type 1 diabetes preclinical models. Transcript profiling of versus BM-MSCs revealed previously unidentified roles for TWIST1/TSG6 in regulating cellular oxidative stress and TGF-β2 in modulating expression and anti-inflammatory activity. and levels also correlate to donor stature and predict differences in iPSC-derived MSC quality attributes. These results validate and as biomarkers that predict interdonor differences in potency across laboratories and assay platforms, thereby providing a means to manufacture MSC products tailored to specific diseases.