Gene therapy holds a major promise. However, until now, this promise was fulfilled only in few cases, in rare genetic diseases. One very common clinical condition is anemia. Patients with anemia of chronic renal failure are treated with erythropoietin. The objective of this study was to develop a therapeutic platform for serum-secreted proteins like erythropoietin. We developed a tissue protein factory based on dermal cores (Biopump) harvested and implanted autologously. In this study, an adenovector was designed to express the human erythropoietin under the control of the cytomegalovirus (CMV) promoter. This vector transduced the harvested dermal cores ex vivo. The transduced cores were implanted, and erythropoietin and reticulocyte counts were measured. Dermal cores were harvested from 13 patients with chronic renal failure, and implantation was performed in 10. There were no significant drug-related side effects to this procedure. Erythropoietin serum levels increased significantly to therapeutic levels from day 1 after implantation reaching a peak during the first week of follow-up.
There have been many attempts to produce animal models that mimic the hypertensive disorders of pregnancy, especially preeclampsia, but most are incomplete when compared to the full spectrum of the human disease. This review assesses a number of these models, organized according to the investigators attempt to focus on a specific pathogenic mechanism believed to play a role in the human disease. These mechanisms include uterine ischemia, impairments in the nitric oxide system, insulin resistance, overactivity of the autonomic nervous and/or renin-angiotensin systems, activation of a systemic inflammatory response, and most recently, activation of circulating proteins that interfere with angiogenesis. In addition a model of renal disease that mimics superimposed preeclampsia is discussed. Defining these animal models should help in our quest to understand the cause, as well as to test preventative and therapeutic strategies in the management of these hypertensive disorders of pregnancy.
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