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Biomedical subjects

W Merrill

Publications and source records attributed to W Merrill.

21 records · Page 2Linked to original sources

Enhanced growth of canine bone marrow stromal cell cultures in the presence of acidic fibroblast growth factor and heparin.

The ex vivo establishment, expansion, transduction, and reintroduction of autologous bone marrow stromal cells offers a potential efficacious system for somatic cell gene therapy. It is likely that any ex vivo system will require the use of large numbers of cells which express high levels of transgene products. We present a method for routine expansion of canine bone marrow stromal cells, established from initial 10-20 ml marrow aspirates, to greater than 10(9) cells. This high level expansion of cell cultures uses the stimulatory effect of acidic fibroblast growth factor (aFGF) and heparin. In the absence of these factors, stromal cell cultures grow actively for only 1 to 2 passages, become flattened in morphology, and expand to only 10(8) cells. In the presence of heparin (5 U/ml), aFGF exerts its effect over a wide range of concentrations (0.1-10 ng/ml) in a dose-dependent manner. The stimulatory effect is dependent on the presence of both aFGF and heparin. Immunocytochemical and cytochemical analyses phenotypically characterize these stromal cells as bone marrow stromal myofibroblasts. Stromal cells grown in the presence of aFGF and heparin grow actively and maintain a fibroblast-like morphology for a number of passages, transduce efficiently with a human growth hormone (hGH) expression vector, and express and secrete high levels of hGH. Human marrow stromal cells were also established and expanded by the same culture method. This culture method should be of great value in somatic cell gene therapy for the delivery of secreted gene products to the plasma of large mammals.

Animals

Relationship of cardiac allograft size and pulmonary vascular resistance to long-term cardiopulmonary function.

The purpose of this study was to evaluate the long-term cardiopulmonary function of heart transplant patients who received disproportionately sized allografts for varying levels of pulmonary vascular resistance. Resting hemodynamics and oxygen uptake during exercise were recorded at 1 year after transplantation in 52 patients. No differences in resting heart rate, cardiac output, stroke volume, peak oxygen uptake during exercise, and exercise duration were found in recipients of undersized hearts (donor:recipient weight ratio [D:R] < 0.75), sized-matched hearts (D:R = 0.75 to 1.25), and oversized (D:R > 1.25) hearts. In a further analysis according to preoperative pulmonary vascular resistance, resting cardiac output (5.8 +/- 1.3 L/min) was normal, and peak exercise oxygen uptake (22.7 +/- 8.0 ml/kg/min) was mildly decreased in recipients of size-matched allografts with a pulmonary vascular resistance of less than 3 Wood units (size-matched hearts, with mild or no pulmonary vascular resistance). Of patients with moderate pulmonary hypertension (pulmonary vascular resistance > or = 3 Wood units), resting cardiac output was normal (5.1 +/- 0.6 L/min) in recipients of oversized hearts and was reduced (4.7 +/- 1.0 L/min) in recipients of sized-matched hearts (p < 0.05 versus recipients of size-matched hearts with pulmonary vascular resistance less than 3 Wood units).(ABSTRACT TRUNCATED AT 250 WORDS)

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