Mesenchymal stromal cells (MSC) are promising stem cell therapy for treating cardiovascular and other degenerative diseases. Diabetes affects the functional capability of MSC and impedes cell-based therapy. Despite numerous studies, the impact of diabetes on MSC myocardial reparative activity, metabolic fingerprint, and the mechanism of dysfunction remains inadequately perceived. We demonstrated that the transplantation of diabetic-MSC (db/db-MSC) into the ischemic myocardium of mice does not confer cardiac benefit post-MI. Metabolomic studies identified defective energy metabolism in db/db-MSC. Furthermore, we found that glypican-3 (GPC3), a heparan sulfate proteoglycan, is highly upregulated in db/db-MSC and is involved in metabolic alterations in db/db-MSC via pyruvate kinase M2 (PKM2) activation. GPC3-knockdown reprogrammed-db/db-MSC restored their energy metabolic rates, immunomodulation, angiogenesis, and cardiac reparative activities. Together, these data indicate that GPC3-metabolic reprogramming in diabetic MSC may represent a strategy to enhance MSC-based therapeutics for myocardial repair in diabetic patients.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490746 | PMC |
| http://dx.doi.org/10.1016/j.isci.2024.111021 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Article Synopsis
- PFOS is a chemical frequently used in industries that can enter the environment and is resistant to breakdown, leading to health concerns.
- Recent studies show a link between PFOS exposure in humans and various diseases, highlighting its impact on human health.
- Research indicates that PFOS negatively affects endometrial cell function and morphology, potentially leading to issues with embryo implantation due to mitochondrial damage and alterations in key protein expression.
Interpenetrating networks of fibrillar and amorphous collagen promote cell spreading and hydrogel stability.
Acta Biomater
January 2025
Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA. Electronic address:
Hydrogels composed of collagen, the most abundant protein in the human body, are widely used as scaffolds for tissue engineering due to their ability to support cellular activity. However, collagen hydrogels with encapsulated cells often experience bulk contraction due to cell-generated forces, and conventional strategies to mitigate this undesired deformation often compromise either the fibrillar microstructure or cytocompatibility of the collagen. To support the spreading of encapsulated cells while preserving the structural integrity of the gels, we present an interpenetrating network (IPN) of two distinct collagen networks with different crosslinking mechanisms and microstructures.
View Article and Find Full Text PDFPrecision medicine in diagnosis, prognosis, and disease monitoring of bone and soft tissue sarcomas using liquid biopsy: a systematic review.
Arch Orthop Trauma Surg
January 2025
Department of Orthopaedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036, Graz, Austria.
Introduction: Liquid biopsy as a non-invasive method to investigate cancer biology and monitor residual disease has gained significance in clinical practice over the years. Whilst its applicability in carcinomas is well established, the low incidence and heterogeneity of bone and soft tissue sarcomas explains the less well-established knowledge considering liquid biopsy in these highly malignant mesenchymal neoplasms.
Materials And Methods: A systematic literature review adhering to the PRISMA guidelines initially identified 920 studies, of whom 68 original articles could be finally included, all dealing with clinical applicability of liquid biopsy in sarcoma.
Chemoresistance in Pancreatic Cancer: The Role of Adipose-Derived Mesenchymal Stem Cells and Key Resistance Genes.
Int J Mol Sci
January 2025
Regenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary.
Drug resistance is a significant challenge in pancreatic ductal adenocarcinoma (PDAC), where stromal elements such as adipose-derived mesenchymal stem cells (ASCs) contribute to a chemoresistant tumor microenvironment (TME). This study explored the effects of oxaliplatin (OXP) and 5-fluorouracil (5-FU) on PDAC cells (Capan-1) and ASCs to investigate the mechanisms of chemoresistance. While OXP and 5-FU reduced Capan-1 viability in a dose- and time-dependent manner, ASCs demonstrated high resistance, maintaining > 90% viability even at cytotoxic doses.
View Article and Find Full Text PDFPreconditioning with Wound Fluid Enhances Immunosuppressive Properties of Mesenchymal Stromal Cells In Vitro.
Int J Mol Sci
December 2024
IZKF Research Group Tissue Regeneration in Musculoskeletal Diseases, University Hospital Wuerzburg, D-97070 Wuerzburg, Germany.
Immunosuppression is one key feature of mesenchymal stromal cells (MSCs) that has high expectations for therapeutic use. The influence of pro-inflammatory stimuli can modify the characteristics of MSCs and enhance immunosuppressive properties. The local postoperative environment contains cytokines, MSCs, and immune cells in high quantities, and their mutual influence is still unclear.
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!