title: Insulin-producing cells from embryonic stem cells rescues hyperglycemia via intra-spleen migration.
abstract: Implantation of embryonic stem cells (ESC)-derived insulin-producing cells has been extensively investigated for treatment of diabetes in animal models. However, the in vivo behavior and migration of transplanted cells in diabetic models remains unclear. Here we investigated the location and migration of insulin-producing cells labeled with superparamagnetic iron oxide (SPIO) using a dynamic MRI tracking method. SPIO labeled cells showed hypointense signal under the kidney subcapsules of diabetic mice on MRI, and faded gradually over the visiting time. However, new hypointense signal appeared in the spleen 1 week after transplantation, and became obvious with the time prolongation. Further histological examination proved the immigrated cells were insulin and C-peptide positive cells which were evenly distributed throughout the spleen. These intra-spleen insulin-producing cells maintained their protective effects against hyperglycemia in vivo, and these effects were reversed upon spleen removal. Transplantation of insulin-producing cells through spleen acquired an earlier blood glucose control as compared with that through kidney subcapsules. In summary, our data demonstrate that insulin-producing cells transplanted through kidney subcapsules were not located in situ but migrated into spleen, and rescues hyperglycemia in diabetic models. MRI may provide a novel tracking method for preclinical cell transplantation therapy of diabetes continuously and non-invasively.
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou. 510120, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ren
authors.affiliation: Department of Hepatology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou. 510120, China.
authors.forename: Changzhen
authors.initials: C
authors.lastname: Shang
authors.affiliation: Department of Radiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou. 510120, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Radiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou. 510120, China.
authors.forename: Ruomi
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou. 510120, China.
authors.forename: Guojuan
authors.initials: G
authors.lastname: Lao
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou. 510120, China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou. 510120, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Hepatology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou. 510120, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Min
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou. 510120, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Radiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou. 510120, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
mesh_terms: D064591:Allografts; D000818:Animals; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D013154:Spleen / Q000378:metabolism* / Q000473:pathology