title: A preclinical evaluation of alternative site for islet allotransplantation.
abstract: The bone marrow cavity (BMC) has recently been identified as an alternative site to the liver for islet transplantation. This study aimed to compare the BMC with the liver as an islet allotransplantation site in diabetic monkeys. Diabetes was induced in Rhesus monkeys using streptozocin, and the monkeys were then divided into the following three groups: Group1 (islets transplanted in the liver with immunosuppressant), Group 2 (islets transplanted in the tibial BMC), and Group 3 (islets transplanted in the tibial BMC with immunosuppressant). The C-peptide and blood glucose levels were preoperatively measured. An intravenous glucose tolerance test (IVGTT) was conducted to assess graft function, and complete blood cell counts were performed to assess cell population changes. Cytokine expression was measured using an enzyme-linked immune sorbent assay (ELISA) and MILLIPLEX. Five monkeys in Group 3 exhibited a significantly increased insulin-independent time compared with the other groups (Group 1: 78.2 ± 19.0 days; Group 2: 58.8 ± 17.0 days; Group 3: 189.6 ± 26.2 days) and demonstrated increases in plasma C-peptide 4 months after transplantation. The infusion procedure was not associated with adverse effects. Functional islets in the BMC were observed 225 days after transplantation using the dithizone (DTZ) and insulin/glucagon stains. Our results showed that allogeneic islets transplanted in the BMC of diabetic Rhesus monkeys remained alive and functional for a longer time than those transplanted in the liver. This study was the first successful demonstration of allogeneic islet engraftment in the BMC of non-human primates (NHPs).
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Chengshi
authors.identifier: http://orcid.org/0000-0002-0650-4109
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, West China Hospital, Sichuan University, Chengdu, P R China.
authors.forename: Xiaojiong
authors.initials: X
authors.lastname: Du
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Sirong
authors.initials: S
authors.lastname: He
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Han
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Younan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Vascular Surgery, West China Hospital, Sichuan University, Chengdu, P R China.
authors.forename: Bole
authors.initials: B
authors.lastname: Tian
authors.affiliation: Animal Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Center for Transplant and Renal Research, The Westmead Institute for Medical Research, Westmead Hospital, Westmead, New South Wales, Australia.
authors.forename: Shounan
authors.initials: S
authors.lastname: Yi
authors.affiliation: Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Fabao
authors.initials: F
authors.lastname: Gao
authors.affiliation: National Center for Safety Evaluation of Traditional Chinese Medicine, Chengdu, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: National Center for Safety Evaluation of Traditional Chinese Medicine, Chengdu, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jingqiu
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D001786:Blood Glucose; D016026:Bone Marrow Transplantation; D002096:C-Peptide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007515:Islets of Langerhans / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D008099:Liver / Q000254:growth & development* / Q000473:pathology; D008253:Macaca mulatta; D013977:Tibia / Q000637:transplantation; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007166:Immunosuppressive Agents