Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice.
Insulin-dependent diabetes mellitus (IDDM) is characterized by the rapid development of potentially severe metabolic abnormalities resulting from insulin deficiency. The transplantation of insulin-producing cells is a promising approach for the treatment of IDDM. The transcription factor pancreatic duodenal homeobox 1 (Pdx1) plays an important role in the differentiation of pancreatic beta cells. In this study, the human Pdx1 gene was transduced and expressed in murine adipose tissue-derived stem cells (ASCs). To evaluate pancreatic repair, we used a mouse model of pancreatic damage resulting in hyperglycemia, which involves injection of mice with streptozotocin (STZ). STZ-treated mice transplanted with Pdx1-transduced ASCs (Pdx1-ASCs) showed significantly decreased blood glucose levels and increased survival, when compared with control mice. While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype in vitro in our experiment, the transplanted stem cells became engrafted in the pancreas, wherein they expressed insulin and C-peptide, which is a marker of insulin-producing cells. These results suggest that Pdx1-ASCs are stably engrafted in the pancreas, acquire a functional beta-cell phenotype, and partially restore pancreatic function in vivo. The ease and safety associated with extirpating high numbers of cells from adipose tissues support the applicability of this system to developing a new cell therapy for IDDM.
Kajiyama
Hiromitsu
H
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.
Hamazaki
Tatsuo S
TS
Tokuhara
Makoto
M
Masui
Shinji
S
Okabayashi
Koji
K
Ohnuma
Kiyoshi
K
Yabe
Shigeharu
S
Yasuda
Kazuki
K
Ishiura
Shoichi
S
Okochi
Hitoshi
H
Asashima
Makoto
M
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D003920:Diabetes Mellitus / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000628:therapy; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013311:Streptozocin / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*
D002096:C-Peptide; D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D013311:Streptozocin