Hydrojet-based delivery of footprint-free iPSC-derived cardiomyocytes into porcine myocardium

Abstract

The reprogramming of patient´s somatic cells into induced pluripotent stem cells (iPSCs) and the consecutive differentiation into cardiomyocytes enables new options for the treatment of infarcted myocardium. In this study, the applicability of a hydrojet-based method to deliver footprint-free iPSC-derived cardiomyocytes into the myocardium was analyzed. A new hydrojet system enabling a rapid and accurate change between high tissue penetration pressures and low cell injection pressures was developed. Iron oxide-coated microparticles were ex vivo injected into porcine hearts to establish the application parameters and the distribution was analyzed using magnetic resonance imaging. The influence of different hydrojet pressure settings on the viability of cardiomyocytes was analyzed. Subsequently, cardiomyocytes were delivered into the porcine myocardium and analyzed by an in vivo imaging system. The delivery of microparticles or cardiomyocytes into porcine myocardium resulted in a widespread three-dimensional distribution. In vitro, 7 days post-injection, only cardiomyocytes applied with a hydrojet pressure setting of E20 (79.57 ± 1.44%) showed a significantly reduced cell viability in comparison to the cells applied with 27G needle (98.35 ± 5.15%). Furthermore, significantly less undesired distribution of the cells via blood vessels was detected compared to 27G needle injection. This study demonstrated the applicability of the hydrojet-based method for the intramyocardial delivery of iPSC-derived cardiomyocytes. The efficient delivery of cardiomyocytes into infarcted myocardium could significantly improve the regeneration.

Clinical Outcomes by Consolidation of Bone Marrow Stem Cell Therapy and Coronary Artery Bypass Graft in Patients With Heart Failure With Reduced Ejection Fraction: A Meta-analysis

“…Whether the stem cells are injected using intracoronary (IC) or intramyocardial (IM), the localization of stem cells is a problem to be solved. Weber et al 32 described a hydrojet-based technique to transplant cardiomyocytes which derived from footprint-free induced pluripotent stem cells (iPSCs) into myocardium. As a more precise and less invasive way to transplant stem cells, hydrojet-based technique has the potential to be a superior approach to traditional needle-based injections (eg, IC or IM) in future CABG procedures or other cell-based therapies.…”

miR-199a Overexpression Enhances the Potency of Human Induced-Pluripotent Stem-Cell–Derived Cardiomyocytes for Myocardial Repair

“…Researchers have also begun to develop techniques for transdifferentiating fibroblasts directly into cardiomyocytes ( Sadahiro 2019 ), which suggests that endogenous cardiac fibroblasts could be a viable target for regenerative myocardial therapy, but the efficiency of the transdifferentiation procedure is exceptionally low. Thus, the transplantation of cardiomyocytes differentiated from human embryonic stem cells or, especially, hiPSCs ( Romagnuolo et al, 2019 ; Sadahiro 2019 ; Yoshida et al, 2020 ) continues to be among the most promising strategies for regenerative myocardial therapy ( Yoshida and Yamanaka 2017 ; Samak and Hinkel 2019 ; Weber et al, 2020 ). Nevertheless, despite substantial evidence that hiPSC-CMs tend to more closely resemble fetal cardiomyocytes than the cardiomyocytes of adult animals ( Robertson, Tran, and George 2013 ), their intrinsic cell-cycle activity remains limited and, consequently, the small number of transplanted hiPSC-CMs that are typically retained and survive at the site of administration cannot substantially remuscularize the myocardial scar ( Isomi, Sadahiro, and Ieda 2019 ).…”

Injection of Porcine Adipose Tissue-Derived Stromal Cells by a Novel Waterjet Technology

“…For WJ injections of pADSCs, vital cell yields of 84.7% and 74.8% were reported for WJ and WN, respectively [ 12 ]. Another study demonstrated no significant difference between WN and WJ (both about 95%) [ 17 ]. This demonstrates a high reproducibility of a standardized injection protocol as is realized by WJ compared to needle injections, where the outcome is dependent on the size of the syringe and needle, the pressure of the syringe, flow rate, and the physician who executes the injection itself.…”

“…The data presented and validated by our study focused primarily on in vitro investigations that pave the way for future in vivo studies. Future research efforts will focus on not only addressing SUI [12,18] but also on other forms of incontinence and pathologies such as heart attack [17]. Overall, the WJ technology satisfies several key considerations required in a clinical context, such as the ease of loading and use, reproducibility of delivery, and precise delivery of viable cells under guided visual control.…”