1,721,176 research outputs found
Myocardial regenerative properties of macrophage populations and stem cells
No full textThe capacity to regenerate damaged tissue and appendages is lost to some extent in higher vertebrates such as mammals, which form a scar tissue at the expenses of tissue reconstitution and functionality. Whereas this process can protect from further damage and elicit fast healing, it can lead to functional deterioration in organs such as the heart. Based on the analyses performed in the last years, stem cell therapies may not be sufficient to induce cardiac regeneration and additional approaches are required to overcome scar formation. Among these, the immune cells and their humoral response have become a key parameter in regenerative processes. In this review, we will describe the recent findings on the possible therapeutical use of progenitor and immune cells to rescue a damaged heart. © 2012 The Author(s)
The role of local Insulin-like Growth Factor-1 isoforms in the pathophysiology of skeletal muscle
No full textStem Cells and the Regenerating Heart
No full textIn response to functional stress, the heart can increase its muscle mass through cellular hypertrophy, but a damaged heart needs a rapid response to repair damage to the muscle wall and maintain adequate blood flow to the rest of the body. In contrast to the mammalian skeletal muscle that regenerates injured tissue through activation of quiescent myogenic precursor or multipotent adult stem cell populations, the heart does not appear to retain equivalent reserve cell populations to promote myofiber repair. The relative scarcity of progenitor cells residing in the adult myocardium has prompted a search for a renewable source of circulating somatic progenitor cells that might home to the heart in response to damage. The capacity of the heart to regenerate may not be a common attribute shared by all cardiomyocytes. Although longitudinal analyses of single cultured new cardiomyocytes revealed that many cells enter into S phase in response to serum-activated pathways dependent on the phosphorylation of the Rb protein, the majority of these cells stablely arrest at either entry to mitosis or during cytokinesis. After surgical removal of the ventricular apex and rapid clotting at the site of amputation, proliferating cardiac myofibers replace the clot and regenerate missing tissue, with minimal scarring. The requirement for cell cycle reentry in this model is supported by the decreased regeneration and increased fibrosis in a temperature-sensitive mutant of a mitotic checkpoint kinase, mps. It is still formally possible that the activation of cardiac progenitor cells is largely responsible for the extraordinary capacity of the adult zebrafish to restore extensive portions of the heart
Advances in stem cell research: use of stem cells in animal models of muscular dystrophy.
No full textEditors: Stevenson, Marshall, Morga
Stem Cells and the Regenerating Heart
No full textThe restricted regenerative capacity of the mammalian heart remains a perplexing exception. The regenerative response launched by other injured organs involves local populations of self-renewing precursor cells, or recruitment of circulating stem cells to replace or repair the injured areas. In response to functional stress, the heart can increase its muscle mass through cellular hypertrophy, but the damaged heart needs a rapid response to repair damage to the muscle wall and maintain adequate blood flow to the rest of the body. Paradoxically, this most critical organ cannot restore the muscle loss that accompanies myocardial infarction and ischemia-reperfusion injury. Instead, interruption of the coronary blood supply results in apoptosis and fibrotic scar formation at the cost of functional muscle. As a result, the remaining cardiomyocytes undergo cellular hypertrophy, leading to decompensated function and congestive heart failure, an increasingly prevalent disease in the industrialized world
Regulation of muscle atrophy in aging and disease.
No full textMuscle aging is characterized by a decline in functional performance and restriction of adaptability, due to progressive loss of muscle tissue coupled with a decrease in strength and force output. Together with selective activation ofapoptotic pathways, a hallmark of age-related muscle loss or sarcopenia is the progressive incapacity of regeneration machinery to replace damaged muscle. These characteristics are shared by pathologies involving muscle wasting, such as muscular dystrophies or amyotrophic lateral sclerosis, cancer and AIDS, all characterized by alterations in metabolic and physiological parameters, progressive weakness in specific muscle groups. Modulation ofextracellular agonists, receptors, protein kinases, intermediate molecules, transcription factors and tissue-specific gene expression collectively compromise the functionality of skeletal muscle tissue, leading to muscle degeneration and persistent protein degradation through activation ofproteolytic systems, such as calpain, ubiquitin-proteasome and caspase. Additional decrements in muscle growth factors compromise skeletal muscle growth, differentiation, survival and regeneration. A better understanding of the mechanisms underlying the pathogenesis of muscle atrophy and wasting associated with different diseases has been the objective of numerous studies and represents an important first step for the development of therapeutic approaches. Among these, insulin-like growth factor-1 (IGF-1) has emerged as a growth factor with a remarkably wide range of actions and a tremendous potential as a therapeutic in attenuating the atrophy and frailty associated with muscle aging and diseases. In this chapter we provide an overview of current concepts in muscle atrophy, focusing specifically on the molecular basis of IGF-1 action and survey current gene and cell therapeutic approaches to rescue muscle atrophy in aging and disease
Stem Cells and the Regenerating Heart
No full textThe impediment to adult mammalian cardiac regeneration has been attributed to its distinct embryonic history, and to the relative paucity of progenitor cells residing within the heart. The primitive heart tube, composed of contracting cardiomyocytes lined by a layer of endocardial cells, ensures the establishment of a circulatory system which is critical to support rapid rates of embryonic growth. Actively contracting fetal cardiomyocytes must continue to divide to provide for further growth of the embryonic heart. A recent report shows that the heart possesses regenerating capacities in which stem or precursor cells "refresh" adult mammalian cardiomyocytes after ischemia or pressure overload, but not during aging. Strategies have been proposed to regenerate the heart via cell therapy, combined with tempering the hostile environment of the infarct, by administration of cell survival and antiinflammatory molecules. Important advances in the control of stem cell fate have also moved the field of regenerative medicine closer towards applicable therapies for cardiac muscle regeneration. The field has yet to overcome significant obstacles, including the incomplete cell differentiation of stem cells, the paucity of organ-specific stem cell resources, and the immunogenicity of the transplanted cells. The presence of a circulating cell population that could restore the heart has gained credibility from observations of sex-mismatched cardiac human transplants in which a female heart is transplanted into a male host. Emerging concepts of regeneration as an evolutionary variable are dramatically illustrated by the relatively robust proliferative capacity of the injured heart in other vertebrate species
Growth factor enhancement of cardiac regeneration
No full textThe potential for endogenous or supplementary stem cells to restore the form and function of damaged tissues is particularly promising for overcoming the restricted regenerative capacity of the mammalian heart. To maintain blood circulation, this essential organ needs to launch a rapid response to repair damage of the muscle wall and to prevent muscle loss. The capacity of growth factors to supplement the repair process has been successfully applied to restore the integrity of damaged skeletal muscle, reducing the fibrotic response to injury, and recruiting local populations of self-renewing precursor cells and circulating stem cells. We review the recent evidence that extension of growth factor supplementation to the heart may overcome its inherent regenerative impediments through improvement of the local tissue environment and stimulation of cell replacement, and we speculate on future research directions for treatment of myocardial damage. Copyright © 2006 Cognizant Comm. Corp
- …
