npj Regenerative Medicine, Journal Year: 2024, Volume and Issue: 9(1)
Published: Dec. 19, 2024
Language: Английский
npj Regenerative Medicine, Journal Year: 2025, Volume and Issue: 10(1)
Published: Jan. 22, 2025
Myocardial infarction (MI) causes the loss of millions cardiomyocytes, and current treatments do not address this root issue. New therapies focus on stimulating cardiomyocyte division in adult heart, inspired by regenerative capacities lower vertebrates neonatal mice. This review explores strategies for heart regeneration, offers insights into proliferation, evaluates vivo models, discusses integrating vitro human cardiac models to advance regeneration research.
Language: Английский
Citations
2
Circulation, Journal Year: 2024, Volume and Issue: 149(20), P. 1598 - 1610
Published: May 13, 2024
Defining mechanisms of cardiomyocyte proliferation should guide the understanding endogenous cardiac regeneration and could lead to novel treatments for diseases such as myocardial infarction. In neonatal heart, energy metabolic reprogramming (phenotypic alteration glucose, fatty acid, amino acid metabolism) parallels cell cycle arrest cardiomyocytes. The occurring shortly after birth is associated with alterations in blood oxygen levels, substrate availability, hemodynamic stress, hormone release. adult infarction causes but these changes cannot stimulate sufficient replace those lost by ischemic injury. Some putative pro-proliferative interventions can induce reprogramming. Recent data show that altering enzymes PKM2 [pyruvate kinase 2], LDHA [lactate dehydrogenase A], PDK4 4], SDH [succinate dehydrogenase], CPT1b [carnitine palmitoyl transferase 1b], or HMGCS2 [3-hydroxy-3-methylglutaryl-CoA synthase 2] partially reverse promotes proliferation. How regulates not clearly defined. possible involve biosynthetic pathways from glycolysis shunts epigenetic regulation induced intermediates. Metabolic manipulation represent a new approach regeneration; however, efficacy manipulations requires optimization, molecular targets need be this review, we summarize features, triggers, regulatory networks responsible discuss current critical determinant
Language: Английский
Citations
9
Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12
Published: March 15, 2024
In recent years, stem cells and their secretomes, notably exosomes, have received considerable attention in biomedical applications. Exosomes are cellular secretomes used for intercellular communication. They perform the function of messengers by facilitating transport proteins, lipids, nucleic acids, therapeutic substances. Their biocompatibility, minimal immunogenicity, targetability, stability, engineerable characteristics additionally led to application as drug delivery vehicles. The efficacy exosomes can be improved through surface modification employing functional molecules, including aptamers, antibodies, peptides. Given potential targeted vehicles enhance efficiency treatment while minimizing adverse effects, exhibit promise. Stem considered advantageous sources due distinctive characteristics, regenerative self-renewal capabilities, which make them well-suited transplantation into injured tissues, hence promoting tissue regeneration. However, there notable obstacles that need addressed, immune rejection ethical problems. produced from been thoroughly studied a cell-free strategy avoids many difficulties involved with cell-based therapy regeneration cancer treatment. This review provides an in-depth summary analysis existing knowledge regarding engineering cardiovascular disease (CVD)
Language: Английский
Citations
6
Methods in cell biology, Journal Year: 2025, Volume and Issue: unknown, P. xv - xxi
Published: Jan. 1, 2025
Language: Английский
Citations
0
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: March 24, 2025
Promoting endogenous cardiomyocyte proliferation is a promising strategy for cardiac repair. Identifying key factors that regulate can advance the development of novel therapies heart regeneration. Here, we identify Foxk1 and Foxk2 as regulators proliferation, whose expression declines during postnatal development. Cardiomyocyte-specific knockout or impairs neonatal regeneration after myocardial infarction (MI) injury. AAV9-mediated overexpression extends proliferative window enhances repair in adult mice MI. Mechanistically, drive cell cycle progression by directly activating CCNB1 CDK1 expression, forming CCNB1/CDK1 complex facilitates G2/M transition. Moreover, promote upregulating HIF1α which glycolysis pentose phosphate pathway (PPP), further favors proliferation. These findings establish therapeutic targets Stimulating offers approach treating injuries. authors demonstrate enhancing through activation metabolic reprogramming, presenting potential ischemic disease
Language: Английский
Citations
0
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: April 19, 2025
Adult zebrafish robustly regenerate injured hearts through a complex orchestration of molecular and cellular activities. However, this remarkable process, which is largely non-existent in humans, remains incompletely understood. Here, we utilize integrated spatial transcriptomics (Stereo-seq) single-cell RNA-sequencing (scRNA-seq) to generate spatially-resolved atlas regenerating heart across eight stages. We characterize the cascade cardiomyocyte cell states responsible for producing regenerated myocardium explore potential role tpm4a re-differentiation. Moreover, uncover activation ifrd1 atp6ap2 genes as unique feature regenerative hearts. Lastly, reconstruct 4D "virtual heart" comprising 569,896 cells/spots derived from 36 scRNA-seq libraries 224 Stereo-seq slices. Our comprehensive serves valuable resource cardiovascular regeneration scientific communities their ongoing efforts understand mechanisms underlying vertebrate regeneration.
Language: Английский
Citations
0
Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12
Published: April 28, 2025
The limited capacity of adult mammalian cardiomyocytes to undergo cell division and proliferation is one the key factors contributing heart failure. In newborn mice, cardiac occurs during a brief window, but this proliferative diminishes by 7 days after birth. Current studies on regeneration focused elucidating changes in regulatory within before aiming determine whether potential association between these cycle arrest cardiomyocytes. Facilitating re-entry into or reversing their exit from it represents critical strategy for regeneration. This paper provides an overview role regeneration, briefly describes cardiomyocyte systematically summarizes regulation cardiomyocytes, metabolic mechanisms underlying arrest. Additionally, we highlight development cardiovascular disease drugs targeting status clinical treatment. Our goal outline strategies promoting repair following injury, while also pointing toward future research directions that may offer new technologies prospects treating diseases, such as myocardial infarction, arrhythmia
Language: Английский
Citations
0
Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 769, P. 151933 - 151933
Published: May 2, 2025
Injured human hearts are fibrotic, whereas zebrafish functionally regenerate following myocardial injury. The unique regeneration niche microenvironment has been extensively studied in hearts. However whether this can be extrapolated to humans remains unclear owing significant species differences. We xenografted induced pluripotent stem cell-derived cardiomyocytes (hiCMs) into the cardiac region of one-day post-fertilized embryos and established a xenograft model hiCMs. This used explore behavior hiCMs transplanted Fluctuations fluorescence intensity genetically encoded calcium indicator protein GCaMP indicated that donor were beating. analyzed synchronization + heart. found synchronous beating between host 40 % with GCaMP-hiPSCs. Our chimeric heart potential bridge capacity gap proming future applications.
Language: Английский
Citations
0
Nature Cardiovascular Research, Journal Year: 2025, Volume and Issue: unknown
Published: May 7, 2025
Language: Английский
Citations
0
Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114092 - 114092
Published: April 1, 2024
Macrophages conduct critical roles in heart repair, but the niche required to nurture and anchor them is poorly studied. Here, we investigated macrophage regenerating heart. We analyzed cell-cell interactions through published single-cell RNA sequencing datasets identified a strong interaction between fibroblast/epicardial (Fb/Epi) cells macrophages. further visualized association of macrophages with Fb/Epi blockage response without zebrafish Moreover, found that ptx3a
Language: Английский
Citations
3