Biomedical subjects

Loren J Field

Publications and source records attributed to Loren J Field.

23 records · Page 2Linked to original sources

PubMed2003

Two-photon molecular excitation imaging of Ca2+ transients in Langendorff-perfused mouse hearts.

The ability to image calcium signals at subcellular levels within the intact depolarizing heart could provide valuable information toward a more integrated understanding of cardiac function. Accordingly, a system combining two-photon excitation with laser-scanning microscopy was developed to monitor electrically evoked [Ca(2+)](i) transients in individual cardiomyocytes within noncontracting Langendorff-perfused mouse hearts. [Ca(2+)](i) transients were recorded at depths </=100 microm from the epicardial surface with the fluorescent indicators rhod-2 or fura-2 in the presence of the excitation-contraction uncoupler cytochalasin D. Evoked [Ca(2+)](i) transients were highly synchronized among neighboring cardiomyocytes. At 1 Hz, the times from 90 to 50% (t(90-50%)) and from 50 to 10% (t(50-10%)) of the peak [Ca(2+)](i) were (means +/- SE) 73 +/- 4 and 126 +/- 10 ms, respectively, and at 2 Hz, 62 +/- 3 and 94 +/- 6 ms (n = 19, P < 0.05 vs. 1 Hz) in rhod-2-loaded cardiomyocytes. [Ca(2+)](i) decay was markedly slower in fura-2-loaded hearts (t(90-50%) at 1 Hz, 128 +/- 9 ms and at 2 Hz, 88 +/- 5 ms; t(50-10%) at 1 Hz, 214 +/- 18 ms and at 2 Hz, 163 +/- 7 ms; n = 19, P < 0.05 vs. rhod-2). Fura-2-induced deceleration of [Ca(2+)](i) decline resulted from increased cytosolic Ca(2+) buffering, because the kinetics of rhod-2 decay resembled those obtained with fura-2 after incorporation of the Ca(2+) chelator BAPTA. Propagating calcium waves and [Ca(2+)](i) amplitude alternans were readily detected in paced hearts. This approach should be of general utility to monitor the consequences of genetic and/or functional heterogeneity in cellular calcium signaling within whole mouse hearts at tissue depths that have been inaccessible to single-photon imaging.

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↗

PubMed2003

Cell cycle regulation to repair the infarcted myocardium.

Lower vertebrates such as newt and zebrafish are able to reactivate high levels of cardiomyocyte cell cycle activity in response to experimental injury resulting in apparent regeneration. In contrast, damaged myocardium is replaced by fibrotic scar tissue in higher vertebrates. This process compromises the contractile function of the surviving myocardium, ultimately leading to heart failure. Various strategies are being pursued to augment myocyte number in the diseased hearts. One approach entails the reactivation of cell cycle in surviving cardiomyocytes. Here, we provide a summary of methods to monitor cell cycle activity, and interventions demonstrating positive cell cycle effects in cardiomyocytes as well as discuss the potential utility of cell cycle regulation to augment myocyte number in diseased hearts.

Animals↗

PubMed2002

Cardiomyocyte cell cycle regulation.

Although rapid progress is being made in many areas of molecular cardiology, issues pertaining to the origins of heart-forming cells, the mechanisms responsible for cardiogenic induction, and the pathways that regulate cardiomyocyte proliferation during embryonic and adult life remain unanswered. In the present study, we review approaches and studies that have shed some light on cardiomyocyte cell cycle regulation. For reference, an initial description of cardiomyogenic induction and morphogenesis is provided, which is followed by a summary of published cell cycle analyses during these stages of cardiac ontology. A review of studies examining cardiomyocyte cell cycle analysis and de novo cardiomyogenic induction in the adult heart is then presented. Finally, studies in which cardiomyocyte cell cycle activity was experimentally manipulated in vitro and in vivo are reviewed. It is hoped that this compilation will serve to stimulate thought and experimentation in this intriguing area of cardiomyocyte cell biology.

Animals↗

PubMed2002

Allogeneic stem cells, clinical transplantation and the origins of regenerative medicine.

The therapeutic use of stem cells is a popular topic that is often in the news. Stem cells are of particular relevance to the transplant community, as stem cell-based therapies will probably be derived from allogeneic sources. Stem cells may be obtained from somatic (adult) cell or embryonic cell origin. The ability to establish stem cell lines in vitro means that we can standardize therapeutic grafting applications, which is a prerequisite for the widespread application of stem cell therapy. This attribute also means that we can produce large batches of allogeneic terminally differentiated cells, which can be administered to patients. Three important barriers to the deployment of this therapy currently exist; in addition to the many ethical issues facing the widespread use of stem cell therapy, it is also important to develop methods to derive pure terminally differentiated cells for transplantation and to induce immune tolerance to these allogeneic cells, as daily anti-rejection therapy cannot be justified for many potential applications.

Animals↗