TY - JOUR
T1 - Vector-free in vivo trans-determination of adult hepatic stem cells to insulin-producing cells
AU - Sarkar, Shuvasree
AU - Munshi, Chayan
AU - Chatterjee, Sarmishtha
AU - Mukherjee, Sandip
AU - Bhattacharya, Shelley
N1 - Publisher Copyright:
© 2019, Springer Nature B.V.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - A reduction in the number of functional β-cells is the central pathological event in diabetes. Liver and ventral pancreas differentiates simultaneously in the same general domain of cells within embryonic endoderm. In addition, the precursor cell population being bi-potential may be targeted for either pancreas or liver development. Hepatic stem cells were redirected in vivo to functional insulin producing cells in a acetylaminofluorene–partial hepatectomy (AAF/PH) adult male rat model with/without GLP-1 treatment. In routine H&E histology and immunohistochemistry, stem cells resembled β cells in GLP-1 injected rats. Immunoblots revealed involvement of adenylate cyclase, TLR4 and PDX1 in insulin synthesis. Expression of genes (GLP-1R, MAFA, PDX1, INS1 and INS2) augmented in the GLP-1 treated regenerated liver. Results strongly indicated the key role of GLP-1 in the induction of insulin secretion in trans-determined reprogrammed cell in vivo. The present method being vector free poses no risk of vector spillover in the host and holds promise.
AB - A reduction in the number of functional β-cells is the central pathological event in diabetes. Liver and ventral pancreas differentiates simultaneously in the same general domain of cells within embryonic endoderm. In addition, the precursor cell population being bi-potential may be targeted for either pancreas or liver development. Hepatic stem cells were redirected in vivo to functional insulin producing cells in a acetylaminofluorene–partial hepatectomy (AAF/PH) adult male rat model with/without GLP-1 treatment. In routine H&E histology and immunohistochemistry, stem cells resembled β cells in GLP-1 injected rats. Immunoblots revealed involvement of adenylate cyclase, TLR4 and PDX1 in insulin synthesis. Expression of genes (GLP-1R, MAFA, PDX1, INS1 and INS2) augmented in the GLP-1 treated regenerated liver. Results strongly indicated the key role of GLP-1 in the induction of insulin secretion in trans-determined reprogrammed cell in vivo. The present method being vector free poses no risk of vector spillover in the host and holds promise.
KW - GLP-1
KW - Stem cell
KW - Vector free trans-determination
KW - β-Like cell
UR - http://www.scopus.com/inward/record.url?scp=85066051340&partnerID=8YFLogxK
U2 - 10.1007/s11033-019-04870-z
DO - 10.1007/s11033-019-04870-z
M3 - Article
C2 - 31102150
AN - SCOPUS:85066051340
SN - 0301-4851
VL - 46
SP - 5501
EP - 5509
JO - Molecular Biology Reports
JF - Molecular Biology Reports
IS - 5
ER -