Transplantation Effectiveness of Induced Pluripotent Stem Cells Is Improved by a Fibrinogen Biomatrix in an Experimental Model of Ischemic Heart Failure

Rojas, Sebastián V.; Martens, Andreas; Zweigerdt, Robert; Baraki, Hassina; Rathert, Christian; Schecker, Natalie; Rojas-Hernández, Sara; Schwanke, Kristin; Martin, Ulrich; Haverich, Axel; Kutschka, Ingo

doi:10.1089/ten.tea.2014.0537

Cited by 14 publications

(12 citation statements)

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“…A commonality of most myocardial cell therapy studies is the application of aqueous injection media for cell transfer (12,36). Previously, using fluorescent microspheres ass cell surrogate, we showed that aqueous injections are marked by early injection loss and redistribution from the injection site via venous drainage to the lung (37). Therefore, for this study, fibrinogen as injection vehicle was chosen to retain injected stem cells in the heart.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have addressed that ineffective cell transfer (9), retention (9), engraftment (10,11), and survival (12)(13)(14) are major hurdles for myocardial regeneration by stem cells and might obscure therapy effectiveness. Thus, independently of which stem cell type is chosen, the optimization of these factors is needed to improve stem cell therapy (15,16). For this purpose, noninvasive methods that allow assessing cell viability in vivo after intramyocardial transplantation are indispensable (15,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).…”

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confidence: 99%

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Multimodal Imaging for In Vivo Evaluation of Induced Pluripotent Stem Cells in a Murine Model of Heart Failure

et al. 2016

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Myocardial stem cell therapy in heart failure is strongly dependent on successful cellular transfer, engraftment, and survival. Moreover, massive cell loss directly after intramyocardial injection is commonly observed, generating the need for efficient longitudinal monitoring of transplanted cells in order to develop more efficient transplantation techniques. Therefore, the aim of the present study was to assess viability and cardiac retention of induced pluripotent stem cells after intramyocardial delivery using in vivo bioluminescence analysis (BLI) and magnetic resonance imaging (MRI). Murine induced pluripotent stem cells (iPSCs) were transfected for luciferase reporter gene expression and labeled intracellularly with supraparamagnetic iron oxide particles. Consequently, 5 × 10 cells were transplanted intramyocardially following left anterior descending coronary artery ligation in mice. Cardiac iPSCs were detected using BLI and serial T2* sequences by MRI in a 14-day follow-up. Additionally, infarct extension and left ventricular (LV) function were assessed by MRI. Controls received the same surgical procedure without cell injection. MRI sequences showed a strong MRI signal of labeled iPSCs correlating with myocardial late enhancement, demonstrating engraftment in the infarcted area. Mean iPSC volumes were 4.2 ± 0.4 mm at Day 0; 3.1 ± 0.4 mm at Day 7; and 5.1 ± 0.8 mm after 2 weeks. Thoracic BLI radiance decreased directly after injection from 1.0 × 10 ± 4.2 × 10 (p/s/cm /sr) to 1.0 × 10 ± 4.9 × 10 (p/s/cm /sr) on Day 1. Afterward, BLI radiance increased to 1.1 × 10 ± 4.2 × 10 (p/s/cm /sr) 2 weeks after injection. Cardiac graft localization was confirmed by ex vivo BLI analysis and histology. Left ventricular ejection fraction was higher in the iPSC group (30.9 ± 0.9%) compared to infarct controls (24.0 ± 2.1%; P < 0.05). The combination of MRI and BLI assesses stem cell fate in vivo, enabling cardiac graft localization with evaluation of LV function in myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Multimodal Imaging for In Vivo Evaluation of Induced Pluripotent Stem Cells in a Murine Model of Heart Failure

et al. 2016

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“…Also, they promote migration of endothelial cells and smooth muscle cells and, simultaneously, confer CMs protection from apoptosis. In addition, these materials have low immunogenicity and have anti-inflammatory and pro-angiogenic properties [17,18,20,37,50,53,67,107,108,112,115]. This explains why delivery of stem cells in scaffolds has higher benefits to those delivered in aqueous or in culture media, with regard to cell retention and proliferation as well as structural and functional myocardial recovery.…”

Section: Combination Of Different Stem Cellsmentioning

confidence: 99%

“…However, fibrin is more viscous than fibrinogen and may, in fact, challenge cell injection and cell nutrition. That is why Rojas et al [107] preferred to imprison iPSC in a fibrinogen matrix. Similarly, animals treated with iPSC and fibrinogen displayed improved LVEF in comparison to those treated with iPSC and medium.…”

Section: Combination Of Different Stem Cellsmentioning

confidence: 99%

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

Trindade

Leite‐Moreira

Ferreira-Martins

et al. 2017

International Journal of Cardiology

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Today there is an increasing demand for heart transplantations for patients diagnosed with heart failure. Though, shortage of donors as well as the large number of ineligible patients hurdle such treatment option. This, in addition to the considerable number of transplant rejections, has driven the clinical research towards the field of regenerative medicine. Nonetheless, to date, several stem cell therapies tested in animal models fall by the wayside and when they meet the criteria to clinical trials, subjects often exhibit modest improvements. A main issue slowing down the admission of such therapies in the domain of human trials is the lack of protocol standardization between research groups, which hampers comparison between different approaches as well as the lack of thought regarding the clinical translation. In this sense, given the large amount of reports on stem cell therapy studies in animal models reported in the last 3 years, we sought to evaluate their advantages and limitations towards the clinical setting and provide some suggestions for the forthcoming investigations. We expect, with this review, to start a new paradigm on regenerative medicine, by evoking the debate on how to plan novel stem cell therapy studies with animal models in order to achieve more consistent scientific production and accelerate the admission of stem cell therapies in the clinical setting.

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“…There are different types of stem cells such as embryonic stem cells, adult stem cells, and induced pluripotent stem cells for treatment of CVDs (Table 1). Previous studies have demonstrated therapeutic effects of ESCs differentiated into cardiomyocytes [17] and endothelial cells [18] for myocardial infarction, umbilical-cord-blood-derived MSCs for dilated cardiomyopathy [19], bone-marrow-derived-MSCs for cellular cardiomyoplasty [20], and iPSCs [21] and iPSCs-derived cardiovascular progenitor cells [22], endothelial progenitor cells (EPCs) [23], and cardiac stem cells [24] for myocardial infarction.…”

Section: Cardiovascular Diseases and Stem Cellsmentioning

confidence: 99%

Therapeutic Potential of Stem Cells Strategy for Cardiovascular Diseases

Lee

Kim

Ham

et al. 2016

Stem Cells International

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Despite development of medicine, cardiovascular diseases (CVDs) are still the leading cause of mortality and morbidity worldwide. Over the past 10 years, various stem cells have been utilized in therapeutic strategies for the treatment of CVDs. CVDs are characterized by a broad range of pathological reactions including inflammation, necrosis, hyperplasia, and hypertrophy. However, the causes of CVDs are still unclear. While there is a limit to the currently available target-dependent treatments, the therapeutic potential of stem cells is very attractive for the treatment of CVDs because of their paracrine effects, anti-inflammatory activity, and immunomodulatory capacity. Various studies have recently reported increased therapeutic potential of transplantation of microRNA- (miRNA-) overexpressing stem cells or small-molecule-treated cells. In addition to treatment with drugs or overexpressed miRNA in stem cells, stem cell-derived extracellular vesicles also have therapeutic potential because they can deliver the stem cell-specific RNA and protein into the host cell, thereby improving cell viability. Here, we reported the state of stem cell-based therapy for the treatment of CVDs and the potential for cell-free based therapy.

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Transplantation Effectiveness of Induced Pluripotent Stem Cells Is Improved by a Fibrinogen Biomatrix in an Experimental Model of Ischemic Heart Failure

Abstract: The fibrinogen biomatrix improved cardiac iPSc retention, sustaining functional improvement and cellular refill of infarcted myocardium. Therefore, fibrinogen can be considered an ideal biological scaffold for intramyocardial stem cell transplantations.

Cited by 14 publications

References 46 publications

Multimodal Imaging for In Vivo Evaluation of Induced Pluripotent Stem Cells in a Murine Model of Heart Failure

Multimodal Imaging for In Vivo Evaluation of Induced Pluripotent Stem Cells in a Murine Model of Heart Failure

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

Therapeutic Potential of Stem Cells Strategy for Cardiovascular Diseases

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