Donor Islet Endothelial Cells in Pancreatic Islet Revascularization
- Daniel Nyqvist1⇓,
- Stephan Speier1,
- Rayner Rodriguez-Diaz2,
- R. Damaris Molano2,
- Saša Lipovsek3,
- Marjan Rupnik3,
- Andrea Dicker1,
- Erwin Ilegems1,
- Elsie Zahr-Akrawi2,
- Judith Molina2,
- Maite Lopez-Cabeza2,
- Susana Villate2,
- Midhat H. Abdulreda2,
- Camillo Ricordi1,2,
- Alejandro Caicedo2,
- Antonello Pileggi2 and
- Per-Olof Berggren1,2,4⇓
- 1The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden
- 2Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida
- 3Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia
- 4Division of Integrative Biosciences and Biotechnology, World Class University Program, Pohang University of Science and Technology, Pohang, Korea
- Corresponding authors: Per-Olof Berggren, , and Daniel Nyqvist, .
OBJECTIVE Freshly isolated pancreatic islets contain, in contrast to cultured islets, intraislet endothelial cells (ECs), which can contribute to the formation of functional blood vessels after transplantation. We have characterized how donor islet endothelial cells (DIECs) may contribute to the revascularization rate, vascular density, and endocrine graft function after transplantation of freshly isolated and cultured islets.
RESEARCH DESIGN AND METHODS Freshly isolated and cultured islets were transplanted under the kidney capsule and into the anterior chamber of the eye. Intravital laser scanning microscopy was used to monitor the revascularization process and DIECs in intact grafts. The grafts’ metabolic function was examined by reversal of diabetes, and the ultrastructural morphology by transmission electron microscopy.
RESULTS DIECs significantly contributed to the vasculature of fresh islet grafts, assessed up to 5 months after transplantation, but were hardly detected in cultured islet grafts. Early participation of DIECs in the revascularization process correlated with a higher revascularization rate of freshly isolated islets compared with cultured islets. However, after complete revascularization, the vascular density was similar in the two groups, and host ECs gained morphological features resembling the endogenous islet vasculature. Surprisingly, grafts originating from cultured islets reversed diabetes more rapidly than those originating from fresh islets.
CONCLUSIONS In summary, DIECs contributed to the revascularization of fresh, but not cultured, islets by participating in early processes of vessel formation and persisting in the vasculature over long periods of time. However, the DIECs did not increase the vascular density or improve the endocrine function of the grafts.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db10-1711/-/DC1.
D.N. is currently affiliated with the Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden.
S.S. is currently affiliated with the Center for Regenerative Therapies Dresden and Paul Langerhans Institute Dresden, Dresden University of Technology, Dresden, Germany.
- Received January 7, 2011.
- Accepted July 13, 2011.
- © 2011 by the American Diabetes Association.
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