Endovascular transplantation of mRNA-enhanced mesenchymal stromal cells results in superior therapeutic protein expression in swine heart
| العنوان: | Endovascular transplantation of mRNA-enhanced mesenchymal stromal cells results in superior therapeutic protein expression in swine heart |
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| المؤلفون: | Al-Saadi, Jonathan, Waldén, Mathias, Sandell, Mikael, Sohlmér, Jesper, Grankvist, Rikard, Friberger, Ida, Andersson, Agneta, Carlsten, Mattias, Chien, Kenneth, Lundberg, Johan, Witman, Nevin, Holmin, Staffan |
| المصدر: | Molecular therapy. Methods & clinical development. 32(2) |
| مصطلحات موضوعية: | cardiology, cell transplantation, endovascular intervention, endovascular intramyocardial transplantation, heart failure, mesenchymal stromal cells, modRNA, mRNA drug products, trans-vessel wall device, vascular endothelial growth factor |
| الوصف: | Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- and cell-based therapies to improve cardiac function. The safe and efficient delivery of these therapies to solid organs is challenging. Herein, we demonstrate the feasibility of using an endovascular intramyocardial delivery approach to safely administer mRNA drug products and perform cell transplantation procedures in swine. Using a trans-vessel wall (TW) device, we delivered chemically modified mRNAs (modRNA) and mRNA-enhanced mesenchymal stromal cells expressing vascular endothelial growth factor A (VEGF-A) directly to the heart. We monitored and mapped the cellular distribution, protein expression, and safety tolerability of such an approach. The delivery of modRNA-enhanced cells via the TW device with different flow rates and cell concentrations marginally affect cell viability and protein expression in situ. Implanted cells were found within the myocardium for at least 3 days following administration, without the use of immunomodulation and minimal impact on tissue integrity. Finally, we could increase the protein expression of VEGF-A over 500-fold in the heart using a cell-mediated modRNA delivery system compared with modRNA delivered in saline solution. Ultimately, this method paves the way for future research to pioneer new treatments for cardiac disease. |
| وصف الملف: | |
| URL الوصول: | https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-344800 https://doi.org/10.1016/j.omtm.2024.101225 |
| قاعدة البيانات: | SwePub |
| تدمد: | 23996951 23290501 |
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| DOI: | 10.1016/j.omtm.2024.101225 |