Deducing Insulin-Producing Cells from Goat Adipose Tissue-Derived Mesenchymal Stem Cells

被引:3
作者
Dubey, Amit [1 ]
Saini, Sikander [1 ]
Sharma, Vishal [1 ]
Malik, Hrudananda [1 ]
Kumar, Dinesh [1 ]
De, Arun Kumar [2 ]
Bhattacharya, Debasis [2 ]
Malakar, Dhruba [1 ,3 ]
机构
[1] ICAR Natl Dairy Res Inst, Anim Biotechnol Ctr, Karnal, India
[2] ICAR Cent Isl Agr Res Inst, Anim Sci Div, Port Blair, India
[3] CAR Natl Dairy Res Inst, Anim Biotechnol CentreI, Karnal 132001, India
关键词
adipose tissue; glucose-dependent insulin release; insulin-producing cells; mesenchymal stem cells; goat; PANCREATIC BETA-CELLS; BONE-MARROW; STROMAL CELLS; DIABETES-MELLITUS; DIFFERENTIATION; TRANSPLANTATION; GENERATION; DERIVATION;
D O I
10.1089/cell.2022.0029
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Mesenchymal stem cell is a potent tool for regenerative medicine against control of incurable diseases in human and animals. Diabetes mellitus is one such condition marked with the blood glucose is high due to lack of insulin (INS) hormone secreted by the pancreatic cells. Rare, but sporadic, cases of dysfunctional pancreatic cells in goat as well as the promises of stem cell therapy as an off-the-shelf medicine prompted us to explore the potential of adipose-derived goat mesenchymal stem cells (AD-MSCs) to transdifferentiate into pancreatic islet-like cells. We isolated, in vitro cultured, and characterized the AD-MSCs by expression of MSC-specific markers and differentiation into multiple mesodermal lineage cells. The characterized AD-MSCs were in vitro transdifferentiated into INS-producing islet-like cells using a cocktail of glucose, nicotinamide, activin-A, exendin-4, pentagastrin, retinoic acid, and mercaptoethanol in 3 weeks. The transdifferentiated islet-like cells demonstrated the expression of pancreatic endoderm-specific transcripts PDX1, NGN3, PAX6, PAX4, ISL1, and GLUT2 as well as protein expression of pancreatic and duodenal homeobox 1 (PDX1), INS, and Islets 1 (ISL1). The islet-like cells also demonstrated the significant glucose-dependent INS release with respect to the course of transdifferentiation regime. The study envisaged to create the building material for basic research into mechanism of glucose homeostasis, which may pave road for developments in diabetes drug discovery and regenerative therapies.
引用
收藏
页码:195 / 203
页数:9
相关论文
共 66 条
[1]   Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells [J].
Ahlgren, U ;
Pfaff, SL ;
Jessell, TM ;
Edlund, T ;
Edlund, H .
NATURE, 1997, 385 (6613) :257-260
[2]   Exendin 4 controls insulin production in rat islet beta cells predominantly by potentiation of glucose-stimulated proinsulin biosynthesis at the translational level [J].
Alarcon, C. ;
Wicksteed, B. ;
Rhodes, C. J. .
DIABETOLOGIA, 2006, 49 (12) :2920-2929
[3]   Conditional inactivation of Pax6 in the pancreas causes early onset of diabetes [J].
Ashery-Padan, R ;
Zhou, XL ;
Marquardt, T ;
Herrera, P ;
Toube, L ;
Berry, A ;
Gruss, P .
DEVELOPMENTAL BIOLOGY, 2004, 269 (02) :479-488
[4]   Osteogenic differentiation of noncultured immunoisolated bone marrow-derived CD105+ cells [J].
Aslan, Hadi ;
Zilberman, Yoram ;
Kandel, Leonid ;
Liebergall, Meir ;
Oskouian, Rod J. ;
Gazit, Dan ;
Gazit, Zulma .
STEM CELLS, 2006, 24 (07) :1728-1737
[5]   Effects of transplanted mesenchymal stem cells isolated from Wharton's jelly of caprine umbilical cord on cutaneous wound healing; histopathological evaluation [J].
Azari, Omid ;
Babaei, Homayoon ;
Derakhshanfar, Amin ;
Nematollahi-Mahani, Seyed Noureddin ;
Poursahebi, Raheleh ;
Moshrefi, Mojgan .
VETERINARY RESEARCH COMMUNICATIONS, 2011, 35 (04) :211-222
[6]   Autologous mesenchymal stem cell transplantation in stroke patients [J].
Bang, OY ;
Lee, JS ;
Lee, PH ;
Lee, G .
ANNALS OF NEUROLOGY, 2005, 57 (06) :874-882
[7]   Endogenous, very small embryonic-like stem cells: critical review, therapeutic potential and a look ahead [J].
Bhartiya, Deepa ;
Shaikh, Ambreen ;
Anand, Sandhya ;
Patel, Hiren ;
Kapoor, Sona ;
Sriraman, Kalpana ;
Parte, Seema ;
Unni, Sreepoorna .
HUMAN REPRODUCTION UPDATE, 2017, 23 (01) :41-76
[8]  
Bobis S, 2006, FOLIA HISTOCHEM CYTO, V44, P215
[9]   COMPENSATORY GROWTH OF PANCREATIC BETA-CELLS IN ADULT-RATS AFTER SHORT-TERM GLUCOSE-INFUSION [J].
BONNERWEIR, S ;
DEERY, D ;
LEAHY, JL ;
WEIR, GC .
DIABETES, 1989, 38 (01) :49-53
[10]   Diabetes mellitus in a goat [J].
Braun, U. ;
Gansohr, B. ;
Seidel, M. ;
Dumelin, J. ;
Wenger, B. ;
Schade, B. ;
Pospischil, A. .
SCHWEIZER ARCHIV FUR TIERHEILKUNDE, 2008, 150 (12) :608-612