Transplantation of NIT-1 cells with ectopic FADDdelGFP expression for treatment of streptozotocin-induced diabetes

Ping Hu; Guohua Wang; Sha Wu; Huifen Zhu; Lei Ping; Congyi Wang; Guanxin Shen

doi:10.1080/08916930902887078

Transplantation of NIT-1 cells with ectopic FADDdelGFP expression for treatment of streptozotocin-induced diabetes

Ping Hu
, Guohua Wang
, Sha Wu
, Huifen Zhu
, Lei Ping
, Congyi Wang
, Guanxin Shen^*

^*Corresponding author for this work

Jinan University
Hubei University
Southern Medical University
Huazhong University of Science and Technology
Department of Pathology
Augusta University

Research output: Contribution to journal › Article › peer-review

Abstract

Islet transplantation is considered a therapeutic option for type 1 diabetes (T1D). However, allorejection is one major barrier for the successful islet transplantation. In the present study, we have tested the feasibility of a deletion construct for Fas-associated death domain protein (FADD; without the death effecter domain) fused with green fluorescent protein (FADDdelGFP) for blocking the FasFasL signaling pathway in prevention of transplanted beta cell destruction by allo-rejection in T1D. In vitro studies have shown that NIT-1 cells with ectopic FADDdel expression were resistant to cytokine-induced apoptosis and CTL-mediated lysis. Diabetic Balb/c mice reached normoglycemia promptly and gained weight after transplantation of NIT-1 cells with ectopic FADDdelGFP expression. These recipients showed a significant longer survival time than that of recipients transplanted with NIT cells with ectopic GFP expression only. Our results together suggest that FADDdel could be a useful target for the improvement of islet transplantation for T1D.

Original language	English
Pages (from-to)	424-431
Number of pages	8
Journal	Autoimmunity
Volume	42
Issue number	5
DOIs	https://doi.org/10.1080/08916930902887078
Publication status	Published - 2009
Externally published	Yes

Keywords

Apoptosis
Fas
Fas-associated death domain protein
Islet transplantation
Type 1 diabetes

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10.1080/08916930902887078

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title = "Transplantation of NIT-1 cells with ectopic FADDdelGFP expression for treatment of streptozotocin-induced diabetes",

abstract = "Islet transplantation is considered a therapeutic option for type 1 diabetes (T1D). However, allorejection is one major barrier for the successful islet transplantation. In the present study, we have tested the feasibility of a deletion construct for Fas-associated death domain protein (FADD; without the death effecter domain) fused with green fluorescent protein (FADDdelGFP) for blocking the FasFasL signaling pathway in prevention of transplanted beta cell destruction by allo-rejection in T1D. In vitro studies have shown that NIT-1 cells with ectopic FADDdel expression were resistant to cytokine-induced apoptosis and CTL-mediated lysis. Diabetic Balb/c mice reached normoglycemia promptly and gained weight after transplantation of NIT-1 cells with ectopic FADDdelGFP expression. These recipients showed a significant longer survival time than that of recipients transplanted with NIT cells with ectopic GFP expression only. Our results together suggest that FADDdel could be a useful target for the improvement of islet transplantation for T1D.",

keywords = "Apoptosis, Fas, Fas-associated death domain protein, Islet transplantation, Type 1 diabetes",

author = "Ping Hu and Guohua Wang and Sha Wu and Huifen Zhu and Lei Ping and Congyi Wang and Guanxin Shen",

year = "2009",

doi = "10.1080/08916930902887078",

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T1 - Transplantation of NIT-1 cells with ectopic FADDdelGFP expression for treatment of streptozotocin-induced diabetes

AU - Hu, Ping

AU - Wang, Guohua

AU - Wu, Sha

AU - Zhu, Huifen

AU - Ping, Lei

AU - Wang, Congyi

AU - Shen, Guanxin

PY - 2009

Y1 - 2009

N2 - Islet transplantation is considered a therapeutic option for type 1 diabetes (T1D). However, allorejection is one major barrier for the successful islet transplantation. In the present study, we have tested the feasibility of a deletion construct for Fas-associated death domain protein (FADD; without the death effecter domain) fused with green fluorescent protein (FADDdelGFP) for blocking the FasFasL signaling pathway in prevention of transplanted beta cell destruction by allo-rejection in T1D. In vitro studies have shown that NIT-1 cells with ectopic FADDdel expression were resistant to cytokine-induced apoptosis and CTL-mediated lysis. Diabetic Balb/c mice reached normoglycemia promptly and gained weight after transplantation of NIT-1 cells with ectopic FADDdelGFP expression. These recipients showed a significant longer survival time than that of recipients transplanted with NIT cells with ectopic GFP expression only. Our results together suggest that FADDdel could be a useful target for the improvement of islet transplantation for T1D.

AB - Islet transplantation is considered a therapeutic option for type 1 diabetes (T1D). However, allorejection is one major barrier for the successful islet transplantation. In the present study, we have tested the feasibility of a deletion construct for Fas-associated death domain protein (FADD; without the death effecter domain) fused with green fluorescent protein (FADDdelGFP) for blocking the FasFasL signaling pathway in prevention of transplanted beta cell destruction by allo-rejection in T1D. In vitro studies have shown that NIT-1 cells with ectopic FADDdel expression were resistant to cytokine-induced apoptosis and CTL-mediated lysis. Diabetic Balb/c mice reached normoglycemia promptly and gained weight after transplantation of NIT-1 cells with ectopic FADDdelGFP expression. These recipients showed a significant longer survival time than that of recipients transplanted with NIT cells with ectopic GFP expression only. Our results together suggest that FADDdel could be a useful target for the improvement of islet transplantation for T1D.

KW - Apoptosis

KW - Fas

KW - Fas-associated death domain protein

KW - Islet transplantation

KW - Type 1 diabetes

UR - https://www.scopus.com/pages/publications/70749098581

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DO - 10.1080/08916930902887078

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AN - SCOPUS:70749098581

SN - 0891-6934

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JO - Autoimmunity

JF - Autoimmunity

IS - 5

ER -

Transplantation of NIT-1 cells with ectopic FADDdelGFP expression for treatment of streptozotocin-induced diabetes

Abstract

Keywords

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