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Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 888-893
From the Department of Pediatrics, University of Washington, Seattle,
WA.
To approach the goal of consistent long-term erythropoietin (Epo)
expression in vivo, we developed an implantation procedure in which
transduced autologous vascular smooth muscle was introduced into rats
in a chamber created from a polytetrafluoroethylene (PTFE) ring placed
under the serosa of the stomach. The implant became vascularized and
permitted the long-term survival of smooth muscle cells expressing Epo.
Hematocrits of treated animals increased rapidly and monitored over 12 months gave a mean value of 56.0 ± 4.0% (P < .001; n = 9), increased from a presurgery mean of 42.3 ± 1.6%. Hemoglobin
levels rose from a presurgery mean of 15.2 ± 0.4 g/dL and for 12 months were significantly elevated with a mean value of 19.5 ± 1.3 g/dL (P < .001; n = 9). The hematocrit and
hemoglobin levels of control animals receiving human adenosine deaminase (ADA)-expressing cells were not significantly
different from baseline (P > .05; n = 5). In response to
tissue oxygenation, kidney, and (to a lesser extent) liver are specific
organs that synthesize Epo. Treated animals showed downregulation of
endogenous Epo mRNA in kidney over a 12-month period. The PTFE implant
provides sustained gene delivery, is safe, and is minimally invasive.
It allows easy engraftment of transduced cells and may be applied generally to the systemic delivery of therapeutic proteins such as
hormones and clotting factors.
© 1998 by The American Society of Hematology.
This article has been cited by other articles:
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