Research Articles Transplanted microvessels improve pluripotent stem cell-derived cardiomyocyte engraftment and cardiac function after infarction in rats

Human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) offer an unprecedented opportunity to remuscularize infarcted human hearts. However, studies have shown that most hiPSC-CMs do not survive after transplantation into the ischemic myocardial environment, limiting their regenerative potential and clinical application. We established a method to improve hiPSC-CM survival by cotransplanting ready-made microvessels obtained from adipose tissue. Ready-made microvessels promoted a sixfold increase in hiPSC-CM survival and superior functional recovery when compared to hiPSC-CMs transplanted alone or cotransplanted with a suspension of dissociated endothelial cells in infarcted rat hearts. Microvessels showed unprecedented persistence and integration at both early (~80%, week 1) and late (~60%, week 4) time points, resulting in increased vessel density and graft perfusion, and improved hiPSC-CM maturation. These findings provide an approach to cell-based therapies for myocardial infarction, whereby incorporation of ready-made microvessels can improve functional outcomes in cell replacement therapies.
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research

Related Links:

CONCLUSIONS: ASC sheets prevented cardiac dysfunctions and remodeling after MI in a rat model via VEGF secretion. Inhibition of VEGF effects by carvedilol abolished their beneficial effects. PMID: 31527337 [PubMed - as supplied by publisher]
Source: Circulation Journal - Category: Cardiology Authors: Tags: Circ J Source Type: research
Conclusions: Four weeks after MSCs transplantation for curing AMI, the myocardial perfusion and glucose metabolism improved significantly in the Rapamycin group; however, the cardiac function was decreased. It is speculated that Rapamycin might have impacted the effect of MSCs transplantation in infarcted hearts. The mechanism needs further research. Index on SPECT, PET and MRI in Three GroupsControl group MSCs groupRapamycin groupP valueSRS24.43±5.4728.63±3.3420.50±7.70
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Cardiovascular Basic Science: Metabolism and Molecular Imaging Source Type: research
This study also identified the cardiac myocyte as a significant local source of BDNF, as cardiac myocyte-specific deletion of BDNF induced a similar cardiomyopathy phenotype. While these results do not exclude a role for other neurotrophins, particularly in injury states, they point to the requirement for continued, local synthesis of BDNF to maintain optimal cardiac function. A major, unresolved question relates to how the truncated TrkB isoform (TrkBT1) transduces the inotropic effects of BDNF, which will require additional study. A concurrent study evaluated the potential impact of the BDNF-mediated activation of the k...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Giuseppe Ristagno1*, Francesca Fumagalli1, Barbara Bottazzi2, Alberto Mantovani2,3,4, Davide Olivari1, Deborah Novelli1 and Roberto Latini1 1Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy 2Humanitas Clinical and Research Center-IRCCS, Milan, Italy 3Humanitas University, Milan, Italy 4The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The p...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study indicates that frailty and other age-related diseases could be prevented and significantly reduced in older adults. Getting our heart risk factors under control could lead to much healthier old ages. Unfortunately, the current obesity epidemic is moving the older population in the wrong direction, however our study underlines how even small reductions in risk are worthwhile." The study analysed data from more than 421,000 people aged 60-69 in both GP medical records and in the UK Biobank research study. Participants were followed up over ten years. The researchers analysed six factors that could impa...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusions: Small animal SPECT and PET have the resolution and sensitivity to assess myocardial perfusion in mouse model of MI. As such these techniques could be employed for non-invasive characterization of this standard model which is widely used in drug development research.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Cardiovascular Basic Science Poster Session Source Type: research
In conclusion, senescence of vascular cells promotes the development of age-related disorders, including heart failure, diabetes, and atherosclerotic diseases, while suppression of vascular cell senescence ameliorates phenotypic features of aging in various models. Recent findings have indicated that specific depletion of senescent cells reverses age-related changes. Although the biological networks contributing to maintenance of homeostasis are extremely complex, it seems reasonable to explore senolytic agents that can act on specific cellular components or tissues. Several clinical trials of senolytic agents are currentl...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study provided novel strategy and experimental evidence for the clinical application of biomaterials in stem cell transplantation for treatment of ischemic heart disease such as MI. PMID: 28709866 [PubMed - as supplied by publisher]
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
Abstract An increasing number of patients have refractory angina despite optimal medical therapy and are without further revascularization options. Pre-clinical studies indicate that human CD34(+) stem cells can stimulate new blood vessel formation in ischemic myocardium, improving perfusion and function. In ACT34-CMI (n=167), patients treated with autologous CD34(+) stem cells had improvements in angina and exercise time at 6 and 12 months compared to placebo; however, the longer-term effects of this treatment are unknown. ACT-34 was a phase II randomized, double-blind, placebo-controlled clinical trial comparing...
Source: Cell Transplantation - Category: Cytology Authors: Tags: Cell Transplant Source Type: research
More News: Biomedical Science | Cardiology | Environmental Health | Heart | Heart Attack | Heart Transplant | Perfusion | Science | Stem Cell Therapy | Stem Cells | Study | Transplants