scholarly journals Immunomodulation by systemic administration of human-induced pluripotent stem cell-derived mesenchymal stromal cells to enhance the therapeutic efficacy of cell-based therapy for treatment of myocardial infarction

Theranostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1641-1654
Author(s):  
Si-Jia Sun ◽  
Wing-Hon Lai ◽  
Yu Jiang ◽  
Zhe Zhen ◽  
Rui Wei ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Efficacy ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Systemic Administration ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Preclinical Safety Evaluation of Allogeneic Induced Pluripotent Stem Cell-Based Therapy in a Swine Model of Myocardial Infarction

2017 ◽  
Vol 23 (11) ◽  
pp. 736-744 ◽  
Author(s):  
Carolina Gálvez-Montón ◽  
Carolina Soler-Botija ◽  
Oriol Iborra-Egea ◽  
Idoia Díaz-Güemes ◽  
Mercè Martí ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Safety Evaluation ◽  
Induced Pluripotent Stem Cell ◽  
Swine Model ◽  
Cell Based Therapy ◽  
Induced Pluripotent ◽  
Preclinical Safety

scholarly journals Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, in Contrast to Adipose Tissue-Derived Stromal Cells, Efficiently Improve Heart Function in Murine Model of Myocardial Infarction

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 578
Author(s):  
Jacek Stępniewski ◽  
Mateusz Tomczyk ◽  
Kalina Andrysiak ◽  
Izabela Kraszewska ◽  
Alicja Martyniak ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Therapeutic Effect ◽  
Murine Model ◽  
Stromal Cells ◽  
Pluripotent Stem Cell ◽  
Heart Function ◽  
Genetically Modified ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent

Cell therapies are extensively tested to restore heart function after myocardial infarction (MI). Survival of any cell type after intracardiac administration, however, may be limited due to unfavorable conditions of damaged tissue. Therefore, the aim of this study was to evaluate the therapeutic effect of adipose-derived stromal cells (ADSCs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) overexpressing either the proangiogenic SDF-1α or anti-inflammatory heme oxygenase-1 (HO-1) in a murine model of MI. ADSCs and hiPSCs were transduced with lentiviral vectors encoding luciferase (Luc), GFP and either HO-1 or SDF-1α. hiPSCs were then differentiated to hiPSC-CMs using small molecules modulating the WNT pathway. Genetically modified ADSCs were firstly administered via intracardiac injection after MI induction in Nude mice. Next, ADSCs-Luc-GFP and genetically modified hiPSC-CMs were injected into the hearts of the more receptive NOD/SCID strain to compare the therapeutic effect of both cell types. Ultrasonography, performed on days 7, 14, 28 and 42, revealed a significant decrease of left ventricular ejection fraction (LVEF) in all MI-induced groups. No improvement of LVEF was observed in ADSC-treated Nude and NOD/SCID mice. In contrast, administration of hiPSC-CMs resulted in a substantial increase of LVEF, occurring between 28 and 42 days after MI, and decreased fibrosis, regardless of genetic modification. Importantly, bioluminescence analysis, as well as immunofluorescent staining, confirmed the presence of hiPSC-CMs in murine tissue. Interestingly, the luminescence signal was strongest in hearts treated with hiPSC-CMs overexpressing HO-1. Performed experiments demonstrate that hiPSC-CMs, unlike ADSCs, are effective in improving heart function after MI. Additionally, long-term evaluation of heart function seems to be crucial for proper assessment of the effect of cell administration.

scholarly journals Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage

2022 ◽  
Vol 8 ◽  
Author(s):  
Klaus Neef ◽  
Florian Drey ◽  
Vera Lepperhof ◽  
Thorsten Wahlers ◽  
Jürgen Hescheler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Border Zone ◽  
Left Ventricular Ejection ◽  
Induced Pluripotent

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.

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