Author ORCID Identifier
Date Available
3-18-2024
Year of Publication
2024
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Medicine
Department/School/Program
Pharmacology and Nutritional Sciences
Advisor
Dr. Ahmed Abdel-Latif
Abstract
Heart failure (HF) following myocardial infarction (MI) remains a significant global health concern, with the initial ischemic injury often leading to microvascular damage and infarct expansion, exacerbating the overall cardiac impairment. Despite extensive research, there are currently no effective therapies to limit myocardial damage post-MI, resulting in a substantial number of patients progressing to HF. Stem cell therapy has emerged as a promising approach to modulate cardiac injury and promote healing. However, clinical trials have shown only modest success, underscoring the need for improved strategies to enhance efficacy. Additionally, the lack of significant ventricular regeneration highlights the necessity of targeting alternative pathways for cardiac regeneration. To address these challenges, our study aimed to enhance existing cell-based cardiac therapy and uncover novel cardiac protective mechanisms.
We first investigated the hypothesis that enhancing stem cell cardiac retention improves cardiac protection after myocardial infarction. Mesenchymal stem cell (MSC) therapy has been widely tested in clinical trials to promote healing post-myocardial infarction. However, low cell retention and the need for a large donor cell number in human studies remain a key challenge for clinical translation. To overcome this limitation, we adopted a gelatin methacrylate (gelMA) cell-coating technique that photocross-links gelatin on the individual cell surface at the nanoscale. In a murine MI model, we showed that direct injection of gelMA-MSC results in significantly higher myocardial engraftment 7 days after MI compared to uncoated MSCs. GelMA-MSC further amplified MSC benefits resulting in enhanced cardioprotection.
To identify new cardiac protective and repair mechanisms in adult mammals, we investigated repair in spiny mice (Acomys) after MI in comparison with commonly used inbred and outbred laboratory Mus strains. In contrast to most adults, Acomys has demonstrated superior tissue healing of multiple organs. In response to MI, Acomys demonstrated superior ischemic tolerance and cytoprotection as evidenced by cardiac functional stabilization, higher survival rate, and smaller scar size 50 days after injury compared to the inbred and outbred mouse strains. Overall, these findings demonstrate augmented myocardial preservation in spiny mice post-MI and establish Acomys as a new adult mammalian model for cardiac research.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2024.241
Funding Information
This study was supported by:
1) The National Institutes of Health, Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (no.: 1F31HL151120-01) in 2020.
2) The National Institutes of Health, F99/K00 Transition to Aging Research for Predoctoral Students (no.:1F99AG068525-01) in 2020.
Recommended Citation
peng, hsuan, "Cell-based cardiac repair and the natural cardiac healing in regenerative adult mammal" (2024). Theses and Dissertations--Pharmacology and Nutritional Sciences. 56.
https://uknowledge.uky.edu/pharmacol_etds/56
