Characterization of vector-based delivery of neurogenin-3 in murine diabetes.
Characterization of vector-based delivery of neurogenin-3 in murine diabetes.
复制标题
小鼠糖尿病中神经原素 3 载体递送的表征。
DOI：
10.1089/hum.2013.206
复制
发表时间：
2014
影响因子：
4.2
通讯作者：
Kay,MarkA
中科院分区：
文献类型：
--
作者：
Phillips,Neil;Kay,MarkA
Treatment of type 1 diabetes with gene transfer–induced cellular reprogramming requires a pancreatic transcription factor such asNeurogenin-3(Ngn3) and as of yet unknown component of the adenoviral particle. Despite intensive study, there are many unsolved processes related to the mechanisms and physiological parameters related to diabetes correction using this approach. While we confirm that systemic delivery of adenovirus (Ad)-Ngn3provides long-lasting correction of streptozotocin (STZ)-induced hyperglycemia and restoration of growth curves, we found that insulin levels and glucose tolerance tests are not fully restored. By altering the innate and antigen-specific immune responses, we establish that the former likely plays some role in the reprogramming process. Interestingly, Ad-hNgn3therapy in diabetic animals appeared to protect them from secondary STZ challenge. The resistance to secondary STZ response was more pronounced at later time points, indicating that a period of cell maturation and/or expansion may be required in order to promote lasting correction. More importantly, these results suggest that the long-term reprogrammed cells are not fully reprogrammed into β-cells, which in the case of autoimmune diabetes may be advantageous in a long-term treatment strategy. Finally, we show that the prophylactic administration of Ad-hNgn3before diabetic induction protected mice from developing hyperglycemia, demonstrating the potential for reducing or eliminating disease progression should treatment be initiated early or before onset of symptoms.
