Microvesicles but not exosomes from Pathfinder Cells stimulate functional recovery of the pancreas in a mouse streptozotocin-induced diabetes model

McGuinness, D., Anthony, D. F., Moulisova, V. , MacDonald, A. I., Macintyre, A., Thomson, J., Nag, A., Davies, R. W. and Shiels, P. G. (2016) Microvesicles but not exosomes from Pathfinder Cells stimulate functional recovery of the pancreas in a mouse streptozotocin-induced diabetes model. Rejuvenation Research, 19(3), pp. 223-232. (doi:10.1089/rej.2015.1723)

McGuinness, D., Anthony, D. F., Moulisova, V. , MacDonald, A. I., Macintyre, A., Thomson, J., Nag, A., Davies, R. W. and Shiels, P. G. (2016) Microvesicles but not exosomes from Pathfinder Cells stimulate functional recovery of the pancreas in a mouse streptozotocin-induced diabetes model. Rejuvenation Research, 19(3), pp. 223-232. (doi:10.1089/rej.2015.1723)

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Abstract

Pathfinder cells, a novel cell type derived from the pancreas of adult rats, have been demonstrated to stimulate recovery of tissue structure and function in two animal models of acute tissue damage to date: Streptozotocin induced diabetes and ischemia-reperfusion damage to the kidney. In repaired tissue Pathfinder cells and their progeny typically represent only 0.02% of the repaired tissue, suggesting that they act via a paracrine mechanism on native cells in the damaged area. Extracellular vesicles are strong candidates for mediating such a paracrine effect. Therefore we studied the effects of two Pathfinder cell-derived extracellular vesicle fractions on tissue repair in the Streptozotocin diabetes model, one containing primarily microvesicles and the second containing predominantly exosomes. Treatment of Streptozotocin -induced diabetic mice with the microvesicles preparation led to blood glucose, insulin, glucagon and C-peptide levels similar to those found with Pathfinder cell treatment. Furthermore, analysis of the histopathology of the pancreas indicated islet regeneration. In contrast, the exosome fraction demonstrated no repair activity, and Streptozotocin diabetic mice treated with exosome preparations had blood glucose values which were indistinguishable from those of vehicle-only treated controls. We therefore conclude that exosomes play no part in Pathfinder cell action as detected by this assay, whereas microvesicles provide all or a large component of the paracrine activity of Pathfinder cells. Since they act to stimulate repair of multiple tissues, Pathfinder cell-derived microvesicles may similarly have the potential to stimulate repair of many damaged tissues, identifying a very significant cell-free therapeutic opportunity in regenerative medicine.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Moulisova, Dr Vladimira and McGuinness, Dr Dagmara and Macintyre, Mr Alan and MacDonald, Dr Alasdair and Anthony, Dr Diana and Shiels, Professor Paul and Thomson, Mrs Jacqueline
Authors: McGuinness, D., Anthony, D. F., Moulisova, V., MacDonald, A. I., Macintyre, A., Thomson, J., Nag, A., Davies, R. W., and Shiels, P. G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Rejuvenation Research
Publisher:Mary Ann Liebert, Inc. Publishers
ISSN:1549-1684
ISSN (Online):1557-8577
Published Online:10 February 2016

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