In vitro transdifferentiation of adult pancreatic acinar cells into insulin-expressing cells.
Despite a recent breakthrough in human islet transplantation for treating diabetes mellitus, the limited availability of insulin-producing tissue is still a major obstacle. Here, we studied whether adult pancreatic acinar cells have the potential to transdifferentiate into islet or beta cells. Pancreatic acini were isolated from 7- to 8-weeks-old male Sprague-Dawley rats and cultured in suspension. Within 1 week, most of the acinar cells lost amylase expression and converted to cells with a duct cell phenotype. Insulin-positive cells were also observed, mainly at the periphery of the acini-derived spheroids. Insulin gene and protein expression was increased. Presence of a few insulin-positive cells coexpressing cytokeratins suggests that a spontaneous acinar to ductal cell transdifferentiation process was further going on towards beta cells. This study provides the first evidence that adult pancreatic acinar cells could be differentiated into insulin-expressing cells in vitro.
Song
Ki-Ho
KH
Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea. kihos@vincent.cuk.ac.kr
Ko
Seung Hyun
SH
Ahn
Yu-Bae
YB
Yoo
Soon-Jib
SJ
Chin
Hyung-Min
HM
Kaneto
Hideaki
H
Yoon
Kun-Ho
KH
Cha
Bong-Yun
BY
Lee
Kwang-Woo
KW
Son
Ho-Young
HY
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D053554:Keratin-20; D053552:Keratin-7; D007633:Keratins / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods; D000516:alpha-Amylases / Q000378:metabolism*
D007328:Insulin; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; C507497:KRT7 protein, human; D053554:Keratin-20; D053552:Keratin-7; C489973:Krt20 protein, rat; D007633:Keratins; D000516:alpha-Amylases