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Nerve/glial antigen 2 is crucially involved in the revascularization of freely transplanted pancreatic islets

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Abstract

Pancreatic islets are highly vascularized endocrine units. Accordingly, their adequate revascularization is of major importance for successful islet transplantation. The proteoglycan, nerve/glial antigen 2 (NG2) expressed in pericytes is a crucial regulator of angiogenesis. Therefore, we herein analyze whether this surface protein contributes to the revascularization of grafted islets. Islets were isolated from NG2+/+ (wild-type) and NG2−/− mice and their cellular composition was analyzed by immunohistochemical detection of insulin, glucagon, somatostatin and CD31. Moreover, insulin secretion was assessed by enzyme-linked immunosorbent assay (ELISA). In addition, isolated islets were transplanted into dorsal skinfold chambers of wild-type mice and their revascularization was determined by intravital fluorescence microscopy and immunohistochemistry. NG2+/+ and NG2−/− islets did not differ in their cellular composition and insulin secretion. However, transplanted NG2−/− islets exhibited a significantly lower functional capillary density and a reduced number of CD31-positive microvessels. These findings demonstrate that the loss of NG2 impairs the revascularization of transplanted islets, underlining the importance of this pericytic proteoglycan for islet engraftment.

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Acknowledgments

We are grateful for the excellent technical assistance of Caroline Bickelmann. We gratefully acknowledge Hongkui Zeng (Allen Institute for Brain Science, Seattle, Washington, USA) for providing reporter mice.

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Authors and Affiliations

  1. Institute for Clinical & Experimental Surgery, Saarland University, 66421, Homburg/Saar, Germany

    Lisa Nalbach, Beate M. Schmitt, Vivien Becker, Matthias W. Laschke, Michael D. Menger & Emmanuel Ampofo

  2. Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany

    Anja Scheller

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  1. Lisa Nalbach
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  2. Beate M. Schmitt
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  7. Emmanuel Ampofo
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Correspondence to Emmanuel Ampofo.

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The authors declare that they have no conflict of interest.

All experiments were approved by the local governmental animal protection committee (Landesamt für Verbraucherschutz, Abteilung C Lebensmittel- und Veterinärwesen, Saarbrücken, Germany; permit number 45/2018). They were performed according to the NIH Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, National Research Council, Washington DC, USA) and the European legislation on protection of animals (Guide line 2010/63/EU).

For the generation of human citrate plasma, venous blood was drawn from four healthy human volunteers after obtaining their written informed consent and with the approval of the local ethics review board.

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Nalbach, L., Schmitt, B.M., Becker, V. et al. Nerve/glial antigen 2 is crucially involved in the revascularization of freely transplanted pancreatic islets. Cell Tissue Res 378, 195–205 (2019). https://doi.org/10.1007/s00441-019-03048-0

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