Instructive Biomaterials for Myocardial Regeneration and Repair

2011 ◽  
pp. 289-328
Author(s):  
Emil Ruvinov ◽  
Smadar Cohen
Keyword(s):  
Myocardial Regeneration

PHENOTYPIC HETEROGENEITY OF CARDIAC MACROPHAGES DURING WOUND HEALING FOLLOWING MYOCARDIAL INFARCTION: PERSPECTIVES IN CLINICAL RESEARCH

2018 ◽  
Vol 33 (2) ◽  
pp. 70-76 ◽  
Author(s):  
A. E. Gombozhapova ◽  
Yu. V. Rogovskaya ◽  
M. S. Rebenkova ◽  
J. G. Kzhyshkowska ◽  
V. V. Ryabov
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Cardiac Remodeling ◽  
Phenotypic Heterogeneity ◽  
Macrophage Infiltration ◽  
Myocardial Regeneration ◽  
Control Group ◽  
M2 Macrophage ◽  
Inflammatory Phase ◽  
Regenerative Phase

Purpose. Myocardial regeneration is one of the most ambitious goals in prevention of adverse cardiac remodeling. Macrophages play a key role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). We have accumulated data on macrophage properties ex vivo and in cell culture. However, there is no clear information about phenotypic heterogeneity of cardiac macrophages in patients with MI. The purpose of the project was to assess cardiac macrophage infiltration during wound healing following myocardial infarction in clinical settings taking into consideration experimental knowledge.Material and Methods. The study included 41 patients with fatal MI type 1. In addition to routine analysis, macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163, CD206, and stabilin-1 were considered as M2 macrophage biomarkers. Nine patients who died from noncardiovascular causes comprised the control group.Results. The intensity of cardiac macrophage infiltration was higher during the regenerative phase than during the inflammatory phase. Results of immunohistochemical analysis demonstrated the presence of phenotypic heterogeneity of cardiac macrophages in patients with MI. We noticed that numbers of CD68+, CD163+, CD206+, and stabilin-1+ macrophages depended on MI phase.Conclusion. Our study supports prospects for implementation of macrophage phenotyping in clinic practice. Improved understanding of phenotypic heterogeneity might become the basis of a method to predict adverse cardiac remodeling and the first step in developing myocardial regeneration target therapy.

Nucleated red blood cells participate in myocardial regeneration in the toad Bufo Gargarizan Gargarizan

2021 ◽  
pp. 153537022110132
Author(s):  
Shu-Qin Liu ◽  
Xiao-Ye Hou ◽  
Feng Zhao ◽  
Xiao-Ge Zhao
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Cardiac Injury ◽  
Myocardial Regeneration ◽  
Matrix Metalloproteinase 2 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cardiac Tissues ◽  
Nucleated Red Blood Cells ◽  
Model Animal

Heart regeneration is negligible in humans and mammals but remarkable in some ectotherms. Humans and mammals lack nucleated red blood cells (NRBCs), while ectotherms have sufficient NRBCs. This study used Bufo gargarizan gargarizan, a Chinese toad subspecies, as a model animal to verify our hypothesis that NRBCs participate in myocardial regeneration. NRBC infiltration into myocardium was seen in the healthy toad hearts. Heart needle-injury was used as an enlarged model of physiological cardiomyocyte loss. It recovered quickly and scarlessly. NRBC infiltration increased during the recovery. Transwell assay was done to in vitro explore effects of myocardial injury on NRBCs. In the transwell system, NRBCs could infiltrate into cardiac pieces and could transdifferentiate toward cardiomyocytes. Heart apex cautery caused approximately 5% of the ventricle to be injured to varying degrees. In the mildly to moderately injured regions, NRBC infiltration increased and myocardial regeneration started soon after the inflammatory response; the severely damaged region underwent inflammation, scarring, and vascularity before NRBC infiltration and myocardial regeneration, and recovered scarlessly in four months. NRBCs were seen in the newly formed myocardium. Enzyme-linked immunosorbent assay and Western blotting showed that the levels of tumor necrosis factor-α, interleukin- 1β, 6, and11, cardiotrophin-1, vascular endothelial growth factor, erythropoietin, matrix metalloproteinase- 2 and 9 in the serum and/or cardiac tissues fluctuated in different patterns during the cardiac injury-regeneration. Cardiotrophin-1 could induce toad NRBC transdifferentiation toward cardiomyocytes in vitro. Taken together, the results suggest that the NRBC is a cell source for cardiomyocyte renewal/regeneration in the toad; cardiomyocyte loss triggers a series of biological processes, facilitating NRBC infiltration and transition to cardiomyocytes. This finding may guide a new direction for improving human myocardial regeneration.

Abstract 4830: The Effects of Stem Cells on C-Kit Up-Regulation and Cell-Cycle Reentry of Neonatal Cardiomyocytes are Mediated by IGF-1 Receptor Activation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Xi-Yong Yu ◽  
Yong-Jian Geng ◽  
Xiao-Hong Li ◽  
Chun-Yu Deng ◽  
Shu-Guang Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Inhibitor ◽  
Fold Increase ◽  
Pi3 Kinase ◽  
Myocardial Regeneration ◽  
Akt Kinase ◽  
Paracrine Effects ◽  
Neonatal Cardiomyocytes ◽  
Cell Cycle Reentry ◽  
Secreted Factors

Mesenchymal stem cells (MSCs) contribute myocardial regeneration, and the beneficial effects may be mediated by paracrine factors produced by MSCs. C-kit positive neonatal cardiomyocytes (NCMs) contribute to myocardial regeneration, but they do not give a robust regenerative response since low expression of c-kit. Cell-cycle reentry of NCMs and insulin-like growth factor (IGF-1) improve myocardial function in infarcted hearts. MSCs and NCMs were prepared from Lewis rats, and cocultured in two chambers which allowed the diffusion of secreted factors from upper chamber to lower chamber, but prevented cell contacts. MSCs secreted significant amount of IGF-1 (159.6 ± 34.4 pg/ug DNA at 24 h, 285.3 ± 28.5 pg/ug DNA at 48 h, and 358.3 ± 39.9 pg/ug DNA at 72 h), whereas the amount of IGF-1 in conditioned medium from NCMs was undetectable assessed by IGF-1 ELISA. Using flow cytometry, we found that the secreted factors by MSCs increased c-kit protein expression, which was attenuated by IGF-1 receptor neutralizing antibody (IGF-1R Ab) and phosphatidylinositol 3 (PI3) kinase inhibitor LY 294002 (NCM vs MSC/NCM vs MSC/NCM+IGF-1R Ab vs MSC/NCM+ LY294002= 1.5 ± 0.6 % vs 5.5 ± 0.3 % vs 1.9 ± 0.6% vs 2.1 ± 0.5%) assessed by flow cytometry. The cytokinesis of NCMs was increased when cocultured with MSC analyzed by calcein fluorescence intensity (3.1 ± 0.5 fold increase, p<0.02). As determined by BrdU assay, the DNA synthesis of NCMs was significantly increased when cocultured with MSC compared to NCM alone (1.8 ± 0.3 fold increase at 48 h, 2.6 ± 0.2 fold increae at 72 h), which was attenuated by IGF-1R Ab and by PI3 kinase inhibitor. To confirm the paracrine effects of MSCs are mediated by IGF-1 signaling and PI3/Akt pathway, we performed in vitro Akt kinase assay using GSK-3 fusion protein as substrate, and found that co-culture system increased the activity of Akt kinase in NCMs, and the IGF-1R Ab and PI3 kinase inhibitor dose-dependent blocked the ability of co-culture system to increase Akt kinase activity. Our results demonstrate that the paracrine effects of MSC on c-kit up-regulation and cell-cycle reentry of NCM are mediated by IGF-1R activation through PI3 kinase/Akt - mediated pathway. These findings provide a new paradigm for the biological effects of IGF-1 on myocardial regeneration. This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).

Development of functional hydrogels for heart failure

2019 ◽  
Vol 7 (10) ◽  
pp. 1563-1580 ◽  
Author(s):  
Yanxin Han ◽  
Wenbo Yang ◽  
Wenguo Cui ◽  
Ke Yang ◽  
Xiaoqun Wang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Tissue Engineering ◽  
Cardiac Tissue ◽  
Cardiac Tissue Engineering ◽  
Myocardial Regeneration ◽  
Functional Studies

Hydrogel-based approaches were reviewed for cardiac tissue engineering and myocardial regeneration in ischemia-induced heart failure, with an emphasis on functional studies, translational status, and clinical advancements.

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