دورية أكاديمية
أعرض في EDS

Immunoregulatory Sertoli Cell Allografts Engineered to Express Human Insulin Survive Humoral-Mediated Rejection.

التفاصيل البيبلوغرافية
العنوان: Immunoregulatory Sertoli Cell Allografts Engineered to Express Human Insulin Survive Humoral-Mediated Rejection.
المؤلفون: Washburn RL; Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.; Immunology and Infectious Disease, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA., Hibler T; Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.; Immunology and Infectious Disease, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA., Kaur G; Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.; Department of Medical Education, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA., Sabu-Kurian A; Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA., Landefeld A; Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.; Summer Accelerated Biomedical Research Program, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA., Dufour JM; Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.; Immunology and Infectious Disease, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.; Department of Medical Education, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2022 Dec 14; Vol. 23 (24). Date of Electronic Publication: 2022 Dec 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Diabetes Mellitus, Experimental*/therapy , Diabetes Mellitus, Experimental*/metabolism , Islets of Langerhans Transplantation*, Male ; Humans ; Mice ; Animals ; Sertoli Cells/metabolism ; Insulin/metabolism ; Insulin, Regular, Human ; Complement System Proteins/metabolism ; Immunity ; Allografts ; Graft Rejection
مستخلص: An effective treatment and possible cure for type 1 diabetes is transplantation of pancreatic islets. Unfortunately, transplanted islets are rejected by the immune system with humoral-mediated responses being an important part of rejection. Sertoli cells (SC), an immune regulatory cell shown to survive as allografts long-term without immunosuppressants, have the potential to be used as a cell-based gene therapy vehicle to deliver endogenous insulin-a possible alternative to islets. Previously, we transduced a mouse SC line to produce human insulin. After transplantation into diabetic mice, these cells consistently produced low levels of insulin with graft survival of 75% at 50 days post-transplantation. The object of this study was to assess humoral immune regulation by these engineered SC. Both nontransduced and transduced SC survived exposure to human serum with complement in vitro. Analysis of allografts in vivo at 20 and 50 days post-transplantation revealed that despite IgG antibody detection, complement factor deposition was low and grafts survived through 50 days post-transplantation. Furthermore, the transduced SC secreted elevated levels of the complement inhibitor C1q binding protein. Overall, this suggests SC genetically engineered to express insulin maintain their ability to prevent complement-mediated killing. Since inhibiting complement-mediated rejection is important for graft survival, further studies of how SC modifies the immune response could be utilized to advance the use of genetically engineered SC or to prolong islet allograft survival to improve the treatment of diabetes.
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معلومات مُعتمدة: None CH Foundation
فهرسة مساهمة: Keywords: Sertoli cells; complement; diabetes; genetic engineering; insulin; transplantation
المشرفين على المادة: 0 (Insulin)
0 (Insulin, Regular, Human)
9007-36-7 (Complement System Proteins)
تواريخ الأحداث: Date Created: 20221223 Date Completed: 20221226 Latest Revision: 20221226
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9780793
DOI: 10.3390/ijms232415894
PMID: 36555540
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms232415894