- 作者: Feng-Cheng Chou; Huey-Kang Sytwu
- 作者服務機構: 1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background :
Pancreatic islet transplantation is considered an appropriate treatment to achieve
insulin independence in type I diabetic patients. However, islet isolation and
transplantation-induced oxidative stress and autoimmune-mediated destruction are
still the major obstacles to the long-term survival of graft islets in this potential
therapy. To protect islet grafts from inflammatory damage and prolong their survival,
we transduced islets with an antioxidative gene thioredoxin (TRX) using a lentiviral
vector before transplantation. We hypothesized that the overexpression of TRX in
islets would prolong islet graft survival when transplanted into diabetic non-obese
diabetic (NOD) mice.
Methods :
Islets were isolated from NOD mice and transduced with lentivirus carrying TRX (Lt-
TRX) or enhanced green fluorescence protein (Lt-eGFP), respectively. Transduced
islets were transplanted under the left kidney capsule of female diabetic NOD mice,
and blood glucose concentration was monitored daily after transplantation. The
histology of the islet graft was assessed at the end of the study. The protective effect
of TRX on islets was investigated.
Results :
The lentiviral vector effectively transduced islets without altering the glucosestimulating
insulin-secretory function of islets. Overexpression of TRX in islets
reduced hydrogen peroxide-induced cytotoxicity in vitro. After transplantation into
diabetic NOD mice, euglycemia was maintained for significantly longer in Lt-TRXtransduced
islets than in Lt-eGFP-transduced islets; the mean graft survival was 18 vs.
6.5 days (n = 9 and 10, respectively, p < 0.05).
Conclusions :
We successfully transduced the TRX gene into islets and demonstrated that these
genetically modified grafts are resistant to inflammatory insult and survived longer in
diabetic recipients. Our results further support the concept that the reactive oxygen
species (ROS) scavenger and antiapoptotic functions of TRX are critical to islet
survival after transplantation. - 中文關鍵字: --
- 英文關鍵字: --