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001-es BibID:BIBFORM112329
035-os BibID:(cikkazonosító)632728 (scopus)85108059154 (wos)000657502800001
Első szerző:Pappritz, Kathleen
Cím:Impact of Syndecan-2-Selected Mesenchymal Stromal Cells on the Early Onset of Diabetic Cardiomyopathy in Diabetic db/db Mice / Pappritz Kathleen, Dong Fengquan, Miteva Kapka, Kovacs Arpad, El-Shafeey Muhammad, Kerim Bahtiyar, O'Flynn Lisa, Elliman Stephen Joseph, O'Brien Timothy, Hamdani Nazha, Tschöpe Carsten, Van Linthout Sophie
Dátum:2021
ISSN:2297-055X
Megjegyzések:Background: Mesenchymal stromal cells (MSCs) are an attractive cell type for cell therapy given their immunomodulatory, anti-fibrotic, and endothelial-protective features. The heparin sulfate proteoglycan, syndecan-2/CD362, has been identified as a functional marker for MSC isolation, allowing one to obtain a homogeneous cell product that meets regulatory requirements for clinical use. We previously assessed the impact of wild-type (WT), CD362-, and CD362+ MSCs on local changes in protein distribution in left ventricular (LV) tissue and on LV function in an experimental model of early-onset diabetic cardiomyopathy. The present study aimed to further explore their impact on mechanisms underlying diastolic dysfunction in this model. Materials: For this purpose, 1 ? 106 WT, CD362-, or CD362+ MSCs were intravenously (i.v.) injected into 20-week-old diabetic BKS.Cg-m+/+Leprdb/BomTac, i.e., db/db mice. Control animals (db+/db) were injected with the equivalent volume of phosphate-buffered saline (PBS) alone. After 4 weeks, mice were sacrificed for further analysis. Results: Treatment with all three MSC populations had no impact on blood glucose levels in db/db mice. WT, CD362-, and CD362+ MSC application restored LV nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels in db/db mice, which correlated with a reduction in cardiomyocyte stiffness. Furthermore, all stromal cells were able to increase arteriole density in db/db mice. The effect of CD362+ MSCs on NO and cGMP levels, cardiomyocyte stiffness, and arteriole density was less pronounced than in mice treated with WT or CD362- MSCs. Analysis of collagen I and III protein expression revealed that fibrosis had not yet developed at this stage of experimental diabetic cardiomyopathy. All MSCs reduced the number of cardiac CD3+ and CD68+ cells in db/db mice, whereas only splenocytes from CD362-- and CD362+-db/db mice exhibited a lower pro-fibrotic potential compared to splenocytes from db/db mice. Conclusion: CD362+ MSC application decreased cardiomyocyte stiffness, increased myocardial NO and cGMP levels, and increased arteriole density, although to a lesser extent than WT and CD362- MSCs in an experimental model of early-onset diabetic cardiomyopathy without cardiac fibrosis. These findings suggest that the degree in improvement of cardiomyocyte stiffness following CD362+ MSC application was insufficient to improve diastolic function.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Frontiers in Cardiovascular Medicine. - 8 (2021), p. 1-13. -
További szerzők:Dong, Fengquan Miteva, Kapka Kovács Árpád (1986-) (kardiológus) El-Shafeey, Muhammad Kerim, Bahtiyar O'Flynn, Lisa Elliman, Stephen Joseph O'Brien, Timothy Hamdani, Nazha Tschöpe, Carsten Linthout, Sophie Van
Pályázati támogatás:HEALTH.2012.2.4.3-1
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001-es BibID:BIBFORM109137
035-os BibID:(cikkazonosító)2000050 (scopus)85097417568 (wos)000597239900001
Első szerző:Pappritz, Kathleen
Cím:MALDI-IMS as a Tool to Determine the Myocardial Response to Syndecan-2-Selected Mesenchymal Stromal Cell Application in an Experimental Model of Diabetic Cardiomyopathy / Pappritz Kathleen, Klein Oliver, Dong Fengquan, Hamdani Nazha, Kovacs Arpad, O'Flynn Lisa, Elliman Steve, O'Brien Timothy, Tschöpe Carsten, Van Linthout Sophie
Dátum:2021
ISSN:1862-8346 1862-8354
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Proteomics Clinical Applications. - 15 : 1 (2021), p. 1-10. -
További szerzők:Klein, Oliver Dong, Fengquan Hamdani, Nazha Kovács Árpád (1986-) (kardiológus) O'Flynn, Lisa Elliman, Steve O'Brien, Timothy Tschöpe, Carsten Linthout, Sophie Van
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DOI
Intézményi repozitóriumban (DEA) tárolt változat
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