Neef, Klaus, Drey, Florian, Lepperhof, Vera, Wahlers, Thorsten, Hescheler, Jurgen, Choi, Yeong-Hoon and Saric, Tomo (2022). Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage. Front. Cardiovasc. Med., 8. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2297-055X

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Abstract

Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) represent an attractive resource for cardiac regeneration. However, survival and functional integration of transplanted iPS-CM is poor and remains a major challenge for the development of effective therapies. We hypothesized that paracrine effects of co-transplanted mesenchymal stromal cells (MSCs) augment the retention and therapeutic efficacy of iPS-CM in a mouse model of myocardial infarction (MI). To test this, either iPS-CM, MSC, or both cell types were transplanted into the cryoinfarction border zone of syngeneic mice immediately after injury. Bioluminescence imaging (BLI) of iPS-CM did not confirm enhanced retention by co-application of MSC during the 28-day follow-up period. However, histological analyses of hearts 28 days after cell transplantation showed that MSC increased the fraction of animals with detectable iPS-CM by 2-fold. Cardiac MRI analyses showed that from day 14 after transplantation on, the animals that have received cells had a significantly higher left ventricular ejection fraction (LVEF) compared to the placebo group. There was no statistically significant difference in LVEF between animals transplanted only with iPS-CM or only with MSC. However, combined iPS-CM and MSC transplantation resulted in higher LVEF compared to transplantation of single-cell populations during the whole observation period. Histological analyses revealed that MSC increased the capillarization in the myocardium when transplanted alone or with iPS-CM and decreased the infarct scar area only when transplanted in combination with iPS-CM. These results indicate that co-transplantation of iPS-CM and MSC improves cardiac regeneration after cardiac damage, demonstrating the potential of combining multiple cell types for increasing the efficacy of future cardiac cell therapies.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Neef, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drey, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lepperhof, VeraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wahlers, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, JurgenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Choi, Yeong-HoonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saric, TomoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-669740
DOI: 10.3389/fcvm.2021.794690
Journal or Publication Title: Front. Cardiovasc. Med.
Volume: 8
Date: 2022
Publisher: FRONTIERS MEDIA SA
Place of Publication: LAUSANNE
ISSN: 2297-055X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
THERAPY; COMBINATION; ENGRAFTMENT; INFARCTION; SURVIVAL; REPAIR; BLOOD; MODELMultiple languages
Cardiac & Cardiovascular SystemsMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/66974

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