Yusuf Ali1,2,3, Juan Diez4,5,6, Lars Selander7, Xiaofeng Zheng4,5, Helena Edlund6,8, Per-Olof Berggren7,4,5,6. 1. The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. yusuf.ali@ntu.edu.sg. 2. Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore, 636 921, Republic of Singapore. yusuf.ali@ntu.edu.sg. 3. Singapore Eye Research Institute, The Academia, Singapore, Republic of Singapore. yusuf.ali@ntu.edu.sg. 4. Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore, 636 921, Republic of Singapore. 5. Singapore Eye Research Institute, The Academia, Singapore, Republic of Singapore. 6. Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA. 7. The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 8. Umeå Center for Molecular Medicine, Umeå University, Umeå, Sweden.
Abstract
AIMS/HYPOTHESIS: In vivo imaging of the developing pancreas is challenging due to the inaccessibility of the tissue. To circumvent this, on embryonic day 10.5 (E10.5) we transplanted a mouse developing pancreatic bud into the anterior chamber of the eye (ACE) to determine whether the eye is a useful transplant site to support pancreas development. METHODS: We transplanted an E10.5 dorsal pancreatic bud into the ACE of a syngeneic recipient mouse. Using a mouse insulin promoter-green fluorescent protein (MIP-GFP) mouse as the tissue donor, we non-invasively imaged the pancreatic bud as it develops at single beta cell resolution across time. RESULTS: The transplanted pancreatic bud rapidly engrafts and vascularises when transplanted into the ACE. The pancreatic progenitor cells differentiate into exocrine and endocrine cells, including cells expressing insulin, glucagon and somatostatin. The morphology of the transplanted pancreatic bud resembles that of the native developing pancreas. Beta cells within the transplanted pancreatic bud respond to glucose in a manner similar to that of native fetal beta cells and superior to that of in vitro developed beta cells. Unlike in vitro grown pancreatic explants, pancreatic tissue developing in the ACE is vascularised, providing the developing pancreatic tissue with a milieu resembling the native situation. CONCLUSIONS/ INTERPRETATION: Altogether, we show that the ACE is able to support growth, differentiation and function of a developing pancreatic bud across time in vivo.
AIMS/HYPOTHESIS: In vivo imaging of the developing pancreas is challenging due to the inaccessibility of the tissue. To circumvent this, on embryonic day 10.5 (E10.5) we transplanted a mouse developing pancreatic bud into the anterior chamber of the eye (ACE) to determine whether the eye is a useful transplant site to support pancreas development. METHODS: We transplanted an E10.5 dorsal pancreatic bud into the ACE of a syngeneic recipient mouse. Using a mouse insulin promoter-green fluorescent protein (MIP-GFP) mouse as the tissue donor, we non-invasively imaged the pancreatic bud as it develops at single beta cell resolution across time. RESULTS: The transplanted pancreatic bud rapidly engrafts and vascularises when transplanted into the ACE. The pancreatic progenitor cells differentiate into exocrine and endocrine cells, including cells expressing insulin, glucagon and somatostatin. The morphology of the transplanted pancreatic bud resembles that of the native developing pancreas. Beta cells within the transplanted pancreatic bud respond to glucose in a manner similar to that of native fetal beta cells and superior to that of in vitro developed beta cells. Unlike in vitro grown pancreatic explants, pancreatic tissue developing in the ACE is vascularised, providing the developing pancreatic tissue with a milieu resembling the native situation. CONCLUSIONS/ INTERPRETATION: Altogether, we show that the ACE is able to support growth, differentiation and function of a developing pancreatic bud across time in vivo.
Entities:
Keywords:
Beta cells; Eye transplantation; In vivo imaging; Pancreas development; Pancreatic islets
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