title: The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.
abstract: Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP). The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those immediately following transplantation (p<0.05). Additionally, Tlx1-related genes, including Rrm2b and Pla2g2d, were up-regulated, which indicates that islet grafts expanded in the spleen. The spleen is an ideal candidate for an alternative islet transplantation site because of the resulting reduced inflammation and expansion of the islet graft.
authors.affiliation: Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.|Center for Regenerative Medicine, Fukuoka University Hospital, Fukuoka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nishinakamura
authors.affiliation: Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.|Center for Regenerative Medicine, Fukuoka University Hospital, Fukuoka, Japan.|Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kumano
authors.affiliation: Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.|Center for Regenerative Medicine, Fukuoka University Hospital, Fukuoka, Japan.|Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.|Center for Regenerative Medicine, Fukuoka University Hospital, Fukuoka, Japan.
authors.forename: Shohta
authors.initials: S
authors.lastname: Kodama
mesh_terms: D000818:Animals; D018925:Chemokines / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006943:Hyperglycemia; D007249:Inflammation / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D011169:Portal Vein / Q000502:physiology; D013154:Spleen / Q000502:physiology*; D013311:Streptozocin; D013997:Time Factors
chemical_list: D018925:Chemokines; D018398:Homeodomain Proteins; C487378:Tlx1 protein, mouse; D013311:Streptozocin