Authors:
Hiroshi Yukawa, Hirofumi Noguchi, Koichi Oishi, Yoshitaka Miyamoto, Makoto Inoue, Mamoru Hasegawa, Shuji Hayashi, and Yoshinobu Baba
Summary:
Islet transplantation, including b-cells, has proven to be effective for diabetes in many recent studies; however, this treatment strategy requires sufficient organ donors. One attractive approach for the generation of b-cells is to utilize the expansion and differentiation of cells from pancreatic stem cells (PSCs), which are closely associated to the b-cells lineage. In this study, we investigated whether important transcription factors (Pdx-1, Ngn3, NeuroD, and MafA) in islet cells could be efficiently transduced into mouse PSCs (mPSCs) using Sendai virus (SeV) vectors and found that the transduced cells were differentiated into insulin-producing pancreatic b-cells. The mPSCs transduced with single transcription factors using SeV vectors could not express the insulin-2 mRNA. When combinations of two transcription factors were transduced using the SeV vectors, including combinations of Pdx-1 + NeuroD, Pdx-1 + MafA, and NeuroD + MafA, the expression of insulin-2 mRNA was low but could be detected. When combinations of three or more transcription factors were transduced using SeV vectors, the expression of insulin-2 mRNA could be detected. In particular, the transduction of the combination of PDX-1, NeuroD, and MafA produced the most effective for the expression of insulin-2 mRNA out of all of the different combinations examined. These data suggest that the transduction of transcription factors using SeV vectors facilitates mPSC differentiation into insulin-producing cells and showed the possibility of regenerating b-cells by using transduced PSCs.
Source:
Cell Medicine; Vol. 3, Issue 1, 51-61 (2012)