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Human versus porcine tissue sourcing for an injectable myocardial matrix hydrogel

机译:人和猪组织的可注射心肌基质水凝胶

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Heart failure (HF) after myocardial infarction (MI) is a leading cause of death in the western world with a critical need for new therapies. A previously developed injectable hydrogel derived from porcine myocardial matrix (PMM) has had successful results in both small and large animal MI models. In this study, we sought to evaluate the impact of tissue source on this biomaterial, specifically comparing porcine and human myocardium sources. We first developed an analogous hydrogel derived from human myocardial matrix (HMM). The biochemical and physical properties of the PMM and HMM hydrogels were then characterized, including residual dsDNA, protein content, sulfated glycosaminoglycan (sGAG) content, complex viscosity, storage and loss moduli, and nano-scale topography. Biochemical activity was investigated with in vitro studies for the proliferation of vascular cells and differentiation of human cardiomyocyte progenitor cells (hCMPCs). Next, in vivo gelation and material spread were confirmed for both PMM and HMM after intramyocardial injection. After extensive comparison, the matrices were found to be similar, yet did show some differences. Because of the rarity of collecting healthy human hearts, the increased difficulty in processing the human tissue, shifts in extracellular matrix (ECM) composition due to aging, and significant patient-to-patient variability, these studies suggest that the HMM is not a viable option as a scalable product for the clinic; however, the HMM has potential as a tool for in vitro cell culture.
机译:心肌梗死(MI)后的心力衰竭(HF)是西方世界主要的死亡原因,因此急需新疗法。先前开发的源自猪心肌基质(PMM)的可注射水凝胶在小型和大型动物MI模型中均取得了成功的结果。在这项研究中,我们试图评估组织来源对该生物材料的影响,特别是比较猪和人心肌来源。我们首先开发了源自​​人类心肌基质(HMM)的类似水凝胶。然后表征了PMM和HMM水凝胶的生化和物理特性,包括残留的dsDNA,蛋白质含量,硫酸化糖胺聚糖(sGAG)含量,复数粘度,储能和损耗模量以及纳米级形貌。通过体外研究对血管细胞的增殖和人心肌祖细胞(hCMPCs)的分化进行了生化活性研究。接下来,确认了心肌内注射后PMM和HMM的体内凝胶化和物质扩散。经过广泛的比较,发现矩阵相似,但确实存在一些差异。由于收集健康人心脏的稀有性,处理人体组织的难度增加,由于衰老引起的细胞外基质(ECM)成分的变化以及患者之间的显着差异,这些研究表明HMM不是可行的可选择作为诊所的可扩展产品;然而,HMM有潜力作为体外细胞培养的工具。

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