AI Article Synopsis
- Heart degenerative diseases are hard to treat because the heart has a poor ability to regenerate lost cells called cardiomyocytes.
- Direct cellular reprogramming using small molecules offers a safer way to create functional cardiomyocytes without modifying genes, but the current methods are not very efficient and lead to immature cells.
- This study found that delivering mitochondria from high-energy organs can improve the maturity and functionality of chemically induced cardiomyocyte-like cells (CiCMs), which may enhance their potential use in regenerative medicine.
Article Abstract
Heart degenerative diseases pose a significant challenge due to the limited ability of native heart to restore lost cardiomyocytes. Direct cellular reprogramming technology, particularly the use of small molecules, has emerged as a promising solution to prepare functional cardiomyocyte through faster and safer processes without genetic modification. However, current methods of direct reprogramming often exhibit low conversion efficiencies and immature characteristics of the generated cardiomyocytes, limiting their use in regenerative medicine. This study proposes the use of mitochondrial delivery to metabolically reprogram chemically induced cardiomyocyte-like cells (CiCMs), fostering enhanced maturity and functionality. Our findings show that mitochondria sourced from high-energy-demand organs (liver, brain, and heart) can enhance structural maturation and metabolic functions. Notably, heart-derived mitochondria resulted in CiCMs with a higher oxygen consumption rate capacity, enhanced electrical functionality, and higher sensitivity to hypoxic condition. These results are related to metabolic changes caused by increased number and size of mitochondria and activated mitochondrial fusion after mitochondrial treatment. In conclusion, our study suggests that mitochondrial delivery into CiCMs can be an effective strategy to promote cellular maturation, potentially contributing to the advancement of regenerative medicine and disease modeling.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604293 | PMC |
| http://dx.doi.org/10.1002/mco2.70005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A self-assembled fluorescent nanoprobe recognized by FA1 site for specifically selecting HSA: Its applications in hemin detection, cell imaging and fluorescent tracing drug delivery.
Bioorg Chem
December 2024
Pancreas Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China. Electronic address:
As naturally essential biomacromolecule, HSA has become diagnostic indicators for various diseases and universal carriers for anticancer drug delivery, therefore, fluorescence detection and labeling for HSA possess significant application value in the biomedical field. In this paper, hydrazide Schiff base fluorescent probe NDQC was designed and synthesized, which self-assembled into nanoparticles in aqueous solution system and demonstrated excellent selectivity and sensitivity towards HSA. Through displacement assay and molecular docking simulation, the binding of NDQC with HSA in FA1 site was demonstrated, thereby no obvious fluorescence signal presented for homologous protein BSA due to their structural differences in binding site.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Background: Despite recent FDA approvement of disease-modifying treatments that reduce Aβ, the identification of novel therapeutic strategies that could delay the Alzheimer's disease (AD) development are needed. We identified and developed novel small molecule compounds that mildly inhibit mitochondrial complex I (MCI). Chronic treatment with a tool compound CP2 in 4 mouse models of familial AD was efficacious protecting against synaptic dysfunction and memory impairment, improving brain energetics and cognitive performance, reducing levels of human pTau and Ab.
View Article and Find Full Text PDFMitochondria-Targeting Virus-Like Gold Nanoparticles Enhance Chemophototherapeutic Efficacy Against Pancreatic Cancer in a Xenograft Mouse Model.
Int J Nanomedicine
January 2025
Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People's Republic of China.
Background: The dense and fibrotic nature of the pancreatic tumor microenvironment significantly contributes to tumor invasion and metastasis. This challenging environment acts as a formidable barrier, hindering effective drug penetration and delivery, which ultimately limits the efficacy of conventional cancer treatments. Gold nanoparticles (AuNPs) have emerged as promising nanocarriers to overcome the extracellular matrix barrier; however, their limited targeting precision, poor delivery efficiency, and insufficient photothermal conversion present challenges.
View Article and Find Full Text PDFA multifunctional mitochondria-protective gene delivery platform promote intervertebral disc regeneration.
Biomaterials
December 2024
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, China. Electronic address:
Intervertebral disc degeneration (IDD) is a deleterious condition driven by localized inflammation and the associated disruption of the normal homeostatic balance between anabolism and catabolism, contributing to progressive functional abnormalities within the nucleus pulposus (NP). Despite our prior evidence demonstrating that a miR-21 inhibitor can have regenerative effects that counteract the progression of IDD, its application for IDD treatment remains limited by the inadequacy of current local delivery systems. Here, an injectable tannic acid (TA)-loaded hydrogel gene delivery system was developed and used for the encapsulation of a multifunctional mitochondria-protecting gene nanocarrier (PHs).
View Article and Find Full Text PDFNanotechnology-Enhanced Pharmacotherapy for Intervertebral Disc Degeneration Treatment.
Int J Nanomedicine
January 2025
Department of Hand Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an Honghui Hospital North District, Xi'an, Shaanxi, 710000, People's Republic of China.
Intervertebral disc degeneration (IDD) is a primary contributor to chronic back pain and disability globally, with current therapeutic approaches often proving inadequate due to the complex nature of its pathophysiology. This review assesses the potential of nanoparticle-driven pharmacotherapies to address the intricate challenges presented by IDD. We initially analyze the primary mechanisms driving IDD, with particular emphasis on mitochondrial dysfunction, oxidative stress, and the inflammatory microenvironment, all of which play pivotal roles in disc degeneration.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!