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Rutger J Hassink

Publications and source records attributed to Rutger J Hassink.

8 recordsLinked to original sources
PubMed2006

Patterning the heart, a template for human cardiomyocyte development.

Although in mice, the dynamics of gene expression during heart development is well characterized, information on humans is scarce due to the limited availability of material. Here, we analyzed the transcriptional distribution of Mlc-2a, Mlc-1v, Mlc-2v, and atrial natriuretic factor (ANF) in human embryonic hearts between 7 and 18 weeks of gestation and in healthy and hypertrophic adult hearts by in situ hybridization and compared expression with that in mice. Strikingly, Mlc-2a, Mlc-1v, and ANF, which are essentially chamber-restricted in mice by mid-gestation, showed a broader distribution in humans. On the other hand, Mlc-2v may prove to be an adequate ventricular marker in humans in contrast to mouse. This study emphasizes the importance of careful comparative human-animal analyses during embryonic development and adulthood, as avoiding erroneous extrapolations may be critical to develop new and successful myocardial replacement therapies.

Animals↗
PubMed2003

Morphology of atrial myocardium in human pulmonary veins: a postmortem analysis in patients with and without atrial fibrillation.

OBJECTIVES: We report an in-depth postmortem morphologic analysis of atrial myocardium in human pulmonary veins (PVs) from patients with and without atrial fibrillation (AF). BACKGROUND: Electrophysiologic studies established the critical role of PVs in the initiation of AF. To date, a paucity of data exists about PV morphology as an arrhythmogenic substrate. METHODS: Longitudinal tissue-strips of PVs were excised and histologically analyzed from the distal part to just beyond the atriovenous junction in the left atrium from 20 patients, obtained at autopsy. Anatomical measurements, including diameters, lengths, and wall-thicknesses of PVs, obtained at autopsy, were made. RESULTS: Histological analysis revealed extension of atrial myocardium into 89% of all PVs. Prevalence of myocardial extension was significantly higher in veins of 6 patients with compared with 14 patients without AF. Other significant differences in the histology of PVs between the two groups were a higher frequency of discontinuity and hypertrophy and a higher degree of fibrosis of the atrial myocardium in the PVs of patients with AF. A marked variation existed in anatomical dimensions of PVs, although no differences were observed between patients with or without AF. CONCLUSIONS: Atrial myocardium was more often present in the PVs of patients with compared with patients without AF. In the first group, the atrial myocardium in the PVs was characterized by more severe discontinuity, hypertrophy, and fibrosis. A marked variation in anatomical dimensions of the PVs existed.

Adolescent↗
PubMed2003

Transplantation of cells for cardiac repair.

The inability of adult cardiomyocytes to divide to a significant extent and regenerate the myocardium after injury leads to permanent deficits in the number of functional cells, which can contribute to the development and progression of heart failure. The transplantation of skeletal myoblasts or stem cells or cardiomyocytes derived from them into the injured myocardium is a novel and promising approach in the treatment of cardiac disease and the restoration of myocardial function. In this article, skeletal myoblasts and embryonic and bone marrow stem cells are discussed in the context of their potential therapeutic use in cardiac failure. The state of the art in both laboratory and clinic is presented. We discuss current and intrinsic limitations of cardiac cellular transplantation and suggest directions for future research.

Animals↗
PubMed2003

Stem cell therapy for ischemic heart disease.

Recent experimental and clinical observations have suggested that cell transplantation could be of therapeutic value for the treatment of heart disease. This approach was based on the idea that transplanted donor cardiomyocytes would integrate with the host myocardium and thereby directly contribute to cardiac function. Surprisingly, the observation that non-cardiomyogenic cells could also improve cardiac function indicates that functional integration of donor cells might not be required to achieve a beneficial effect. More recently, several observations have suggested the presence of a greater than anticipated developmental repertoire in adult-derived stem cells, which, if further validated, would offer unprecedented opportunities for the restoration of cardiac function in diseased hearts. Here, we discuss current issues regarding the potential use of stem cell transplantation for the treatment of ischemic heart disease.

Animals↗
PubMedDate not supplied

The role of stem cells in cardiac regeneration.

After myocardial infarction, injured cardiomyocytes are replaced by fibrotic tissue promoting the development of heart failure. Cell transplantation has emerged as a potential therapy and stem cells may be an important and powerful cellular source. Embryonic stem cells can differentiate into true cardiomyocytes, making them in principle an unlimited source of transplantable cells for cardiac repair, although immunological and ethical constraints exist. Somatic stem cells are an attractive option to explore for transplantation as they are autologous, but their differentiation potential is more restricted than embryonic stem cells. Currently, the major sources of somatic cells used for basic research and in clinical trials originate from the bone marrow. The differentiation capacity of different populations of bone marrow-derived stem cells into cardiomyocytes has been studied intensively. The results are rather confusing and difficult to compare, since different isolation and identification methods have been used to determine the cell population studied. To date, only mesenchymal stem cells seem to form cardiomyocytes, and only a small percentage of this population will do so in vitro or in vivo. A newly identified cell population isolated from cardiac tissue, called cardiac progenitor cells, holds great potential for cardiac regeneration. Here we discuss the potential of the different cell populations and their usefulness in stem cell based therapy to repair the damaged heart.

Animals↗
PubMedDate not supplied

Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures.

Human embryonic stem cells (hESCs) can differentiate into cardiomyocytes, but the efficiency of this process is low. We routinely induce cardiomyocyte differentiation of the HES-2 cell line by coculture with a visceral endoderm-like cell line, END-2, in the presence of 20% fetal calf serum (FCS). In this study, we demonstrate a striking inverse relationship between cardiomyocyte differentiation and the concentration of FCS during HES-2-END-2 coculture. The number of beating areas in the cocultures was increased 24-fold in the absence of FCS compared with the presence of 20% FCS. An additional 40% increase in the number of beating areas was observed when ascorbic acid was added to serum-free cocultures. The increase in serum-free cocultures was accompanied by increased mRNA and protein expression of cardiac markers and of Isl1, a marker of cardiac progenitor cells. The number of beating areas increased up to 12 days after initiation of coculture of HES-2 with END-2 cells. However, the number of alpha-actinin-positive cardiomyocytes per beating area did not differ significantly between serum-free cocultures (503 +/- 179; mean +/- standard error of the mean) and 20% FCS cocultures (312 +/- 227). The stimulating effect of serum-free coculture on cardiomyocyte differentiation was observed not only in HES-2 but also in the HES-3 and HES-4 cell lines. To produce sufficient cardiomyocytes for cell replacement therapy in the future, upscaling cardiomyocyte formation from hESCs is essential. The present data provide a step in this direction and represent an improved in vitro model, without interfering factors in serum, for testing other factors that might promote cardiomyocyte differentiation.

Actinin↗