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

Autor: Lee RH; Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, College Station, TX, 77845, USA., Boregowda SV; Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL, 33458, USA., Shigemoto-Kuroda T; Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, College Station, TX, 77845, USA., Bae E; Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, College Station, TX, 77845, USA., Haga CL; Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL, 33458, USA., Abbery CA; Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, College Station, TX, 77845, USA., Bayless KJ; Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, College Station, TX, 77845, USA., Haskell A; Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, College Station, TX, 77845, USA., Gregory CA; Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, College Station, TX, 77845, USA., Ortiz LA; Department of Environmental Health, University of Pittsburgh, Pittsburgh, PA 15261, USA., Phinney DG; Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL, 33458, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 Nov 10; Vol. 9 (45), pp. eadi2387. Date of Electronic Publication: 2023 Nov 10.
DOI: 10.1126/sciadv.adi2387
Abstrakt: 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 TSG6 expression that TWIST1 and TSG6 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 TWIST1 Hi TSG6 Low versus TWIST Low TSG6 Hi BM-MSCs revealed previously unidentified roles for TWIST1/TSG6 in regulating cellular oxidative stress and TGF-β2 in modulating TSG6 expression and anti-inflammatory activity. TWIST1 and TSG6 levels also correlate to donor stature and predict differences in iPSC-derived MSC quality attributes. These results validate TWIST1 and TSG6 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.
Databáze: MEDLINE
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