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Angiogenic and reparative potency of a human cardiac CD90- mesenchymal subpopulation in heart ischemic model.

Title: Angiogenic and reparative potency of a human cardiac CD90- mesenchymal subpopulation in heart ischemic model.
Authors: Gambini E; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy; Oloker Therapeutics; Piazza Massari 19, 70122 Bari, Italy. Electronic address: egambini@oloker.com.; Rurali E; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Barbagallo V; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Pirola S; Department of Cardiac Surgery, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138 Milan, Italy.; Scopece A; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Biondi A; Department of Cardiac Surgery, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138 Milan, Italy.; Bassetti B; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Casaburo M; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Eramo L; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy; Oloker Therapeutics; Piazza Massari 19, 70122 Bari, Italy.; Marinelli GPA; Oloker Therapeutics; Piazza Massari 19, 70122 Bari, Italy.; Farinello D; Oloker Therapeutics; Piazza Massari 19, 70122 Bari, Italy.; Rodighiero S; Department of Experimental Oncology, Istituto Europeo di Oncologia IRCCS; Via Adamello 16, 20139 Milan, Italy.; D'alessandra Y; Immunology and Functional Genomics Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Chiesa M; Immunology and Functional Genomics Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Spaltro G; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Ricci V; Oloker Therapeutics; Piazza Massari 19, 70122 Bari, Italy; Immunology and Functional Genomics Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Gowran A; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Castiglioni E; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Fileccia D; Department of Cardiac Surgery, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138 Milan, Italy.; Nanci G; Department of Cardiac Surgery, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138 Milan, Italy.; Asgari F; Oloker Therapeutics; Piazza Massari 19, 70122 Bari, Italy.; Polvani G; Department of Cardiac Surgery, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138 Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, VIa della Commenda 10, 20122 Milan, Italy.; Vinci MC; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy.; Pompilio G; Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy; Department of Cardiac Surgery, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138 Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, VIa della Commenda 10, 20122 Milan, Italy.
Source: Translational research : the journal of laboratory and clinical medicine [Transl Res] 2025 Sep; Vol. 283, pp. 22-35. Date of Electronic Publication: 2025 Aug 27.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Elsevier Country of Publication: United States NLM ID: 101280339 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1810 (Electronic) Linking ISSN: 18781810 NLM ISO Abbreviation: Transl Res Subsets: MEDLINE
Imprint Name(s): Original Publication: New York, N.Y. : Elsevier, [2006]-
MeSH Terms: Mesenchymal Stem Cells*/cytology ; Mesenchymal Stem Cells*/metabolism ; Thy-1 Antigens*/metabolism ; Myocardial Ischemia*/therapy ; Myocardial Ischemia*/pathology ; Neovascularization, Physiologic*; Myocardium/pathology ; Myocardial Infarction/therapy ; Humans ; Animals ; Disease Models, Animal ; Mice ; Male ; Mesenchymal Stem Cell Transplantation ; Mice, Inbred C57BL
Abstract: Background: Despite recent significant therapeutic progress, cardiovascular diseases (CVD) remain an unmet clinical, economic, and social burden worldwide. Cell-based therapies have been proposed as therapeutic strategies, however, the overall efficacy was modest.; Objective: We aimed to fully characterize a novel subpopulation of CD90- mesenchymal cells derived from human heart tissue (hCmPC90-) and evaluate its ability to induce cardiac tissue repair and functional recovery.; Methods: We performed a comprehensive phenotypic characterization of the hCmPC90- by flow cytometry and RNA sequencing. A direct comparison of hCmPC90- with previously clinically tested bone marrow- and cardiac-derived cell types, has been conducted both in vitro by means of various assays of angiogenic potency, and in vivo, by testing the ability to ameliorate left ventricular function in a mouse model of acute myocardial infarction (AMI).; Results: hCmPC90- showed distinct surface markers and transcriptional phenotype compared with unselected mesenchymal heart cells (hCmPCs) and the positive CD90 counterpart (hCmPC90+). When human hCmPC90-, hCmPC90+, hCmPC, cardiosphere-derived cells (CDCs), and bone marrow-derived CD34+ cells were functionally tested in vitro, hCmPC90- revealed a superior endothelial differentiation ability, higher anti-inflammatory, cardio-protective capacity, and angiocrine activity. Moreover, hCmPC90- showed specific immune-privileged features. When intramyocardially delivered into infarcted mouse hearts, hCmPC90- outperformed three weeks after injection other clinical-grade cell types, as for left ventricular (LV) function and adverse LV remodeling recovery, infarct size reduction, and vascular density augmentation.; Conclusion: hCmPC90- shows a superior biological potency which deserves clinical exploitation as an advanced therapy medicinal product in the context of refractory ischemic heart disease.; (Copyright © 2025. Published by Elsevier Inc.)
Contributed Indexing: Keywords: Cardioprotection; Cell therapy; Human cardiac progenitor cells; Myocardial infarction; Paracrine activity
Substance Nomenclature: 0 (Thy-1 Antigens)
Entry Date(s): Date Created: 20250829 Date Completed: 20251013 Latest Revision: 20251013
Update Code: 20260130
DOI: 10.1016/j.trsl.2025.08.004
PMID: 40882914
Database: MEDLINE

Journal Article