TC-tet cells are conditionally immortalized pancreatic fere either with the intrinsic mechanism of growth arrest cells which can confer long-term correction of hyperglycepresent in the TC-tet cells or with their normal glucose mia when transplanted in syngeneic streptozocin diabetic dose-dependent insulin secretory activity. Furthermore, mice. The use of these cells for control of type I diabetes Bcl-2 expressing TC-tet cells retained their capacity to in humans will require their encapsulation and transplansecrete insulin under mild hypoxia. Finally, transplantation tation in non-native sites where relative hypoxia and cytoof these cells under the kidney capsule of streptozocin diakines may threaten their survival. In this study we genetibetic C3H mice corrected hyperglycemia for several cally engineered TC-tet cells with the anti-apoptotic gene months. These results demonstrate that the murine TC-Bcl-2 using new lentiviral vectors and showed that it protet cell line can be genetically modified to improve its resisttected this cell line against apoptosis induced by hypoxia, ance against different stress-induced apoptosis while prestaurosporine and a mixture of cytokines (IL-1, IFN-␥ and serving its normal physiological function. These modified TNF-␣). We further demonstrated that Bcl-2 expression cells represent an improved source for cell transplantation permitted growth at higher cell density and with shorter therapy of type I diabetes. doubling time. Expression of Bcl-2, however, did not inter-
Post-traumatic radioulnar synostosis is a rare complication of forearm fracture. Resulting in loss of forearm axial rotation, it is functionally very disabling. The surgical indication, timing of operation, surgical technique, interest and type of adjuvant treatment are all issues with which physicians managing radioulnar synostosis must deal. No therapeutic consensus yet exists, but a wide variety of surgical techniques and adjuvant treatments are suggested. A literature review sought to identify risk factors for synostosis, with a view to prevention and determining a suitable therapeutic attitude in the light of existing data.
Cell encapsulation offers a safe and manufacturable method for the systemic delivery of therapeutic proteins from genetically engineered cells. However, control of dose delivery remains a major issue with regard to clinical application. We generated populations of immortalized murine NIH 3T3 fibroblasts that secrete mouse erythropoietin (Epo) in response to stimulation by doxycycline or mifepristone. Engineered cells were introduced into AN69 hollow fibers, which were implanted in the peritoneal cavity or recipient mice. Animals receiving doxycycline or mifepristone showed stable polyhemia and increased serum Epo concentrations over a 6-month observation period, whereas animals not receiving the inducer drug had normal hematocrits. Epo secretion could be switched on and off, depending on the presence of doxycycline in the drinking water. In contrast, polyhemia was hardly reversible after subcutaneous injections of mifepristone. These data show that a permanent and regulated systemic delivery of a therapeutic protein can be obtained by the in vivo implantation of engineered allogeneic cells immunoprotected in membrane polymers.
This islet lipofection procedure may help achieve the local release of a bioactive peptide in the graft environment and have therapeutic applications in islet transplantation.
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