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State-of-play for cellular therapies in cardiac repair and regeneration.

ABSTRACT: Cardiovascular disease is the primary cause of death around the world. For almost two decades, cell therapy has been proposed as a solution for heart disease. In this article, we report on the "state-of-play" of cellular therapies for cardiac repair and regeneration. We outline the progression of new ideas from the preclinical literature to ongoing clinical trials. Recent data supporting the mechanics and mechanisms of myogenic and paracrine therapies are evaluated in the context of long-term cardiac engraftment. This discussion informs on promising new approaches to indicate future avenues for the field.

SUBMITTER: Vaka R

PROVIDER: S-EPMC9290630 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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State-of-play for cellular therapies in cardiac repair and regeneration.

Vaka Ramana R Davis Darryl R DR

Stem cells (Dayton, Ohio) 20210827 12

Cardiovascular disease is the primary cause of death around the world. For almost two decades, cell therapy has been proposed as a solution for heart disease. In this article, we report on the "state-of-play" of cellular therapies for cardiac repair and regeneration. We outline the progression of new ideas from the preclinical literature to ongoing clinical trials. Recent data supporting the mechanics and mechanisms of myogenic and paracrine therapies are evaluated in the context of long-term ca ...[more]

PMID: 34448513

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Project description:Regenerative medicine is an emerging interdisciplinary field of scientific research that, supported by tissue engineering is, nowadays, a valuable and reliable solution dealing with the actual organs shortage and the unresolved limits of biological or prosthetic materials used in repair and replacement of diseased or damaged human tissues and organs. Due to the improvements in design and materials, and to the changing of clinical features of patients treated for valvular heart disease the distance between the ideal valve and the available prostheses has been shortened. We will then deal with the developing of new tools aiming at replacing or repair cardiac tissues that still represent an unmet clinical need for the surgeons and indeed for their patients. In the effort of improving treatment for the cardiovascular disease (CVD), scientists struggle with the lack of self-regenerative capacities of finally differentiated cardiovascular tissues. In this context, using several converging technological approaches, regenerative medicine moves beyond traditional transplantation and replacement therapies and can restore tissue impaired function. It may also play an essential role in surgery daily routine, leading to produce devices such as injectable hydrogels, cardiac patches, bioresorbable stents and vascular grafts made by increasingly sophisticated biomaterial scaffolds; tailored devices promptly fabricated according to surgeon necessity and patient anatomy and pathology will hopefully represent a daily activity in the next future. The employment of these devices, still far from the in vitro reproduction of functional organs, has the main aim to achieve a self-renewal process in damaged tissues simulating endogenous resident cell populations. In this field, the collaboration and cooperation between cardiothoracic surgeons and bioengineers appear necessary to modify these innovative devices employed in preclinical studies according to the surgeon's needs.

Project description:Heart failure is a progressive deterioration of cardiac pump function over time and is often a manifestation of ischemic injury caused by myocardial infarction (MI). Post-MI, structural remodeling of the infarcted myocardium ensues. Dysregulation of extracellular matrix (ECM) homeostasis is a hallmark of structural cardiac remodeling and is largely driven by cardiac fibroblast activation. While initially adaptive, structural cardiac remodeling leads to irreversible heart failure due to the progressive loss of cardiac function. Loss of pump function is associated with myocardial fibrosis, wall thinning, and left ventricular (LV) dilatation. Surgical revascularization of the damaged myocardium via coronary artery bypass graft (CABG) surgery and/or percutaneous coronary intervention (PCI) can enhance myocardial perfusion and is beneficial. However, these interventions alone are unable to prevent progressive fibrotic remodeling and loss of heart function that leads to clinical end-stage heart failure. Acellular biologic ECM scaffolds can be surgically implanted onto injured myocardial regions during open-heart surgery as an adjunct therapy to surgical revascularization. This presents a novel therapeutic approach to alter maladaptive remodeling and promote functional recovery. Acellular ECM bioscaffolds have been shown to provide passive structural support to the damaged myocardium and also to act as a dynamic bioactive reservoir capable of promoting endogenous mechanisms of tissue repair, such as vasculogenesis. The composition and structure of xenogenic acellular ECM bioscaffolds are determined by the physiological requirements of the tissue from which they are derived. The capacity of different tissue-derived acellular bioscaffolds to attenuate cardiac remodeling and restore ECM homeostasis after injury may depend on such properties. Accordingly, the search and discovery of an optimal ECM bioscaffold for use in cardiac repair is warranted and may be facilitated by comparing bioscaffolds. This review will provide a summary of the acellular ECM bioscaffolds currently available for use in cardiac surgery with a focus on how they attenuate cardiac remodeling by providing the necessary environmental cues to promote endogenous mechanisms of tissue repair.

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State-of-play for cellular therapies in cardiac repair and regeneration.

Publications

State-of-play for cellular therapies in cardiac repair and regeneration.

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