Bacterial Cellulose and ECM Hydrogels: An Innovative Approach for Cardiovascular Regenerative Medicine.

Cardiovascular diseases are considered the leading cause of death in the world, accounting for approximately 85% of sudden death cases. In dogs and cats, sudden cardiac death occurs commonly, despite the scarcity of available pathophysiological and prevalence data. Conventional treatments are not able to treat injured myocardium. Despite advances in cardiac therapy in recent decades, transplantation remains the gold standard treatment for most heart diseases in humans. In veterinary medicine, therapy seeks to control clinical signs, delay the evolution of the disease and provide a better quality of life, although transplantation is the ideal treatment. Both human and veterinary medicine face major challenges regarding the transplantation process, although each area presents different realities. In this context, it is necessary to search for alternative methods that overcome the recovery deficiency of injured myocardial tissue. Application of biomaterials is one of the most innovative treatments for heart regeneration, involving the use of hydrogels from decellularized extracellular matrix, and their association with nanomaterials, such as alginate, chitosan, hyaluronic acid and gelatin. A promising material is bacterial cellulose hydrogel, due to its nanostructure and morphology being similar to collagen. Cellulose provides support and immobilization of cells, which can result in better cell adhesion, growth and proliferation, making it a safe and innovative material for cardiovascular repair.

Mechanisms of Neonatal Heart Regeneration.

PURPOSE OF REVIEW: This review provides an overview of the molecular mechanisms underpinning the cardiac regenerative capacity during the neonatal period and the potential targets for developing novel therapies to restore myocardial loss. RECENT FINDINGS: We present recent advances in the understanding of the molecular mechanisms of neonatal cardiac regeneration and the implications for the development of new cardiac regenerative therapies. During the early postnatal period, several cell types and pathways are involved in cardiomyocyte proliferation including immune response, nerve signaling, extracellular matrix, mitochondria substrate utilization, gene expression, miRNAs, and cell cycle progression. The early neonatal mammalian heart has remarkable regenerative capacity, which is mediated by proliferation of endogenous cardiomyocytes, and is lost when cardiomyocytes stop dividing shortly after birth. A wide array of mechanisms that regulate this regenerative process have been proposed.

Heart Regeneration in the Mexican Cavefish.

Although Astyanax mexicanus surface fish regenerate their hearts after injury, their Pachón cave-dwelling counterparts cannot and, instead, form a permanent fibrotic scar, similar to the human heart. Myocardial proliferation peaks at similar levels in both surface fish and Pachón 1 week after injury. However, in Pachón, this peak coincides with a strong scarring and immune response, and ultimately, cavefish cardiomyocytes fail to replace the scar. We identified lrrc10 to be upregulated in surface fish compared with Pachón after injury. Similar to cavefish, knockout of lrrc10 in zebrafish impairs heart regeneration without affecting wound cardiomyocyte proliferation. Furthermore, using quantitative trait locus (QTL) analysis, we have linked the degree of heart regeneration to three loci in the genome, identifying candidate genes fundamental to the difference between scarring and regeneration. Our study provides evidence that successful heart regeneration entails a delicate interplay between cardiomyocyte proliferation and scarring.

Stem cell, una alternativa al trasplante cardíaco en el tratamiento de la insuficiencia cardíaca / Stem cell, an alternative to heart transplant in the treatment of heart failure

El concepto tradicional mantenido por años sobre la incapacidad del corazón adulto para renovar sus células ha tenido que ser revisado ante la evidencia de los resultados obtenidos por numerosos estudios que demuestran la existencia en el corazón humano de células con capacidad proliferativa. El trasplante cardíaco aunque ha demostrado ser solución definitiva de la insuficiencia cardíaca no es aplicable a todos los pacientes, fundamentalmente por el déficit de donantes, los avances terapéuticos y quirúrgicos, si bien mejoran la calidad de vida, no son capaces de mejorar la contractilidad miocárdica ni sustituir el cardiomiocito. La terapia celular en la regeneración miocárdica surge como una de las estrategias terapéutica con un futuro prometedor en el tratamiento de la insuficiencia cardíaca, aunque no exenta de controversias, lo que obliga a un mayor conocimiento ante su aplicación clínica, lo cual no contrapone el iniciar ensayos clínicos que permitan un avance en esta dirección.

The traditional concept maintained for years on the incapacity of the adult heart to renew its cells had to be reviewed taking into account the results obtained by numerous studies that demonstrate the existence of cells with proliferative capacity in the human heart. Although the heart transplant has proved to be the definitive solution for heart failure, it may not be applied to all patients due mainly to the deficit of donors. The therapeutic and surgical advances improve the quality of life, but they cannot enhance the myocardial contractility, or replace the cardiomyocite. The cellular therapy in the myocardial regeneration appears as one of the strategical therapeutics with a promising future in the treatment of heart failure, even though it is not exempt from controversies that oblige to have a greater knowledge about its clinical application, but do not impede to start making clinical trials that allow to advance in this direction.