Facilitated Engraftment of Isolated Islets Coated With Expanded Vascular Endothelial Cells for Islet Transplantation.
BACKGROUND
Diabetes is complex disease, which involves primary metabolic changes followed by immunological and vascular pathophysiological adjustments. However, it is mostly characterized by an unbalanced decreased number of the β-cells unable to maintain the metabolic requirements and failure to further regenerate newly functional pancreatic islets. The objective of this study was to analyze the properties of the endothelial cells to facilitate the islet cells engraftment after islet transplantation.


METHODS
We devised a co-cultured engineer system to coat isolated islets with vascular endothelial cells. To assess the cell integration of cell-engineered islets, we stained them for endothelial marker CD31 and nuclei counterstained with DAPI dye. We comparatively performed islet transplantations into streptozotocin-induced diabetic mice and recovered the islet grafts for morphometric analyses on days 3, 7, 10, and 30. Blood glucose levels were measured continuously after islet transplantation to monitor the functional engraftment and capacity to achieve metabolic control.


RESULTS
Cell-engineered islets showed a well-defined rounded shape after co-culture when compared with native isolated islets. Furthermore, the number of CD31-positive cells layered on the islet surface showed a direct proportion with engraftment capacities and less TUNEL-positive cells on days 3 and 7 after transplantation.


CONCLUSIONS
We observed that vascular endothelial cells could be functional integrated into isolated islets. We also found that islets that are coated with vascular endothelial cells increased their capacity to engraft. These findings indicate that islets coated with endothelial cells have a greater capacity of engraftment and thus establish a definitely vascular network to support the metabolic requirements.
Department of Physiology, Laboratory of Immunology, Tissue Engineering and Transplant, University Center for Health Sciences, University of Guadalajara, Mexico.
D Alonso
DA
Barba-Gutierrez
Department of Physiology, Laboratory of Immunology, Tissue Engineering and Transplant, University Center for Health Sciences, University of Guadalajara, Mexico.
A
A
Daneri-Navarro
Department of Physiology, Laboratory of Immunology, Tissue Engineering and Transplant, University Center for Health Sciences, University of Guadalajara, Mexico.
J Jesus Alejandro
JJ
Villagomez-Mendez
Department of Organ Reconstruction, Field of Clinical Application, Institute for Frontier Medical Sciences, Kyoto University, Japan.
J
J
Kanamune
Institute of Sciences for Human Reproduction "Vida," Guadalajara, Mexico.
A Karina
AK
Robles-Murillo
Department of Molecular Biology and Genomics, University Center for Health Sciences, University of Guadalajara, Mexico.
S
S
Sanchez-Enriquez
Department of Surgery, Center of Health Sciences, Autonomous University of Aguascalientes, Mexico.
J Rafael
JR
Villafan-Bernal
Department of Physiology, Laboratory of Immunology, Tissue Engineering and Transplant, University Center for Health Sciences, University of Guadalajara, Mexico. Electronic address: jorgerivasmd@yahoo.com.
J D
JD
Rivas-Carrillo
D000818:Animals; D018920:Coculture Techniques / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D042783:Endothelial Cells / Q000166:cytology* / Q000637:transplantation; D005260:Female; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000637:transplantation; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008807:Mice, Inbred BALB C; D011897:Random Allocation