Huntington's disease (HD) is an incurable inherited brain disorder characterised by massive degeneration of striatal neurons, which correlates with abnormal accumulation of misfolded mutant huntingtin (mHTT) protein. Research on HD has been hampered by the inability to study early dysfunction and progressive degeneration of human striatal neurons in vivo. To investigate human pathogenesis in a physiologically relevant context, we transplanted human pluripotent stem cell-derived neural progenitor cells (hNPCs) from control and HD patients into the striatum of new-born mice.
View Article and Find Full Text PDFFibrosis is present in an important proportion of myocardial disorders. Injury activates cardiac fibroblasts, which deposit excess extracellular matrix, increasing tissue stiffness, impairing cardiac function, and leading to heart failure. Clinical therapies that directly target excessive fibrosis are limited, and more effective treatments are needed.
View Article and Find Full Text PDFObjective: To assess the arrhythmic safety profile of the adipose graft transposition procedure (AGTP) and its electrophysiological effects on post-myocardial infarction (MI) scar.
Background: Myocardial repair is a promising treatment for patients with MI. The AGTP is a cardiac reparative therapy that reduces infarct size and improves cardiac function.
Int J Mol Sci
August 2022
Mesenchymal stromal cell-derived extracellular vesicles (MSC-EV) are widely considered as a cell-free therapeutic alternative to MSC cell administration, due to their immunomodulatory and regenerative properties. However, the interaction mechanisms between EV and target cells are not fully understood. The surface glycans could be key players in EV-cell communication, being specific molecular recognition patterns that are still little explored.
View Article and Find Full Text PDFTheranostics
October 2023
Extracellular vesicles (EVs) from mesenchymal stromal cell (MSC) are a potential therapy for cardiac healing after myocardial infarction (MI). Nevertheless, neither their efficient administration nor therapeutic mechanisms are fully elucidated. Here, we evaluate the preclinical efficacy of a tissue engineering approach to locally deliver porcine cardiac adipose tissue MSC-EV (cATMSC-EV) in an acute MI pig model.
View Article and Find Full Text PDFPrimary ventricular fibrillation (PVF) is a life-threatening complication of ST-segment elevation myocardial infarction (STEMI). It is unclear what roles viral infection and/or systemic inflammation may play as underlying triggers of PVF, as a second hit in the context of acute ischaemia. Here we aimed to evaluate whether the circulating virome and inflammatory proteome were associated with PVF development in patients with STEMI.
View Article and Find Full Text PDFExtracellular vesicles (EVs) are becoming promising tools for clinical application, either as sources of disease-specific molecular signatures for the unraveling of disease pathophysiology and establishment of novel biomarkers, or as platforms for cell-free nanotherapy. Yet, an unsolved issue is to define standardized techniques for EV isolation allowing data comparison across laboratories worldwide. Considering the difficulties to find this necessary consensus, it has to be stressed out that the outcome of the downstream analysis might be deeply biased by the isolation method, among other variables.
View Article and Find Full Text PDFBiomed Pharmacother
March 2022
Compelling evidence supports the therapeutic benefit of extracellular vesicles (EVs). EVs are nanostructures with a lipid bilayer membrane that are secreted by multiple cells, including mesenchymal stromal cells (MSCs), as means of cellular communication. MSC-EVs, resembling their MSC origin, carry protected immunomodulatory and pro-regenerative cargoes to targeted neighboring or distant cells and tissues.
View Article and Find Full Text PDFStem cell therapy has an unparalleled potential to treat blood cancers, cardiovascular diseases and neurodegenerative conditions, among others. However, stem cell therapeutics must overcome multiple requirements before reaching clinical trials, including large animal safety and efficacy studies. In cardiovascular diseases swine models are the most widely adopted due to its great translational potential to humans.
View Article and Find Full Text PDFOutstanding progress has been achieved in developing therapeutic options for reasonably alleviating symptoms and prolonging the lifespan of patients suffering from myocardial infarction (MI). Current treatments, however, only partially address the functional recovery of post-infarcted myocardium, which is in fact the major goal for effective primary care. In this context, we largely investigated novel cell and TE tissue engineering therapeutic approaches for cardiac repair, particularly using multipotent mesenchymal stromal cells (MSC) and natural extracellular matrices, from pre-clinical studies to clinical application.
View Article and Find Full Text PDFBioact Mater
October 2021
The administration of extracellular vesicles (EV) from mesenchymal stromal cells (MSC) is a promising cell-free nanotherapy for tissue repair after myocardial infarction (MI). However, the optimal EV delivery strategy remains undetermined. Here, we designed a novel MSC-EV delivery, using 3D scaffolds engineered from decellularised cardiac tissue as a cell-free product for cardiac repair.
View Article and Find Full Text PDFMultipotent mesenchymal stromal cells (MSC) represent a promising strategy for a variety of medical applications. Although only a limited number of MSC engraft and survive after in vivo cellular infusion, MSC have shown beneficial effects on immunomodulation and tissue repair. This indicates that the contribution of MSC exists in paracrine signaling, rather than a cell-contact effect of MSC.
View Article and Find Full Text PDFStem Cell Res Ther
November 2019
Background: Orthopaedic diseases are one of the major targets for regenerative medicine. In this context, Wharton's jelly (WJ) is an alternative source to bone marrow (BM) for allogeneic transplantation since its isolation does not require an invasive procedure for cell collection and does not raise major ethical concerns. However, the osteogenic capacity of human WJ-derived multipotent mesenchymal stromal cells (MSC) remains unclear.
View Article and Find Full Text PDFExtracellular vesicles (EVs) include a variety of nanosized vesicles released to the extracellular microenvironment by the vast majority of cells transferring bioactive lipids, proteins, mRNA, miRNA or non-coding RNA, as means of intercellular communication. Remarkably, among other fields of research, their use has become promising for immunomodulation, tissue repair and as source for novel disease-specific molecular signatures or biomarkers. However, a major challenge is to define accurate, reliable and easily implemented techniques for EV isolation due to their nanoscale size and high heterogeneity.
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