Pathfinder cells provide a novel therapeutic intervention for acute kidney injury

McGlynn, L.M., Eller, K., MacDonald, A.I., MacIntyre, A., Russell, D., Koppelstaetter, C., Davies, R. and Shiels, P.G. (2013) Pathfinder cells provide a novel therapeutic intervention for acute kidney injury. Rejuvenation Research, 16(1), pp. 11-20. (doi: 10.1089/rej.2012.1350)

Abstract

Pathfinder cells (PCs) are a novel class of adult-derived cells that facilitate functional repair of host tissue. We used rat PCs to demonstrate that they enable the functional mitigation of ischemia reperfusion (I/R) injury in a mouse model of renal damage. Female C57BL/6 mice were subjected to 30 min of renal ischemia and treated with intravenous (i.v.) injection of saline (control) or male rat pancreas-derived PCs in blinded experimentation. Kidney function was assessed 14 days after treatment by measuring serum creatinine (SC) levels. Kidney tissue was assessed by immunohistochemistry (IHC) for markers of cellular damage, proliferation, and senescence (TUNEL, Ki67, p16ink4a, p21). Fluorescence in situ hybridization (FISH) was performed to determine the presence of any rat (i.e., pathfinder) cells in the mouse tissue. PC-treated animals demonstrated superior renal function at day 14 post-I/R, in comparison to saline-treated controls, as measured by SC levels (0.13 mg/dL vs. 0.23 mg/dL, p<0.001). PC-treated kidney tissue expressed significantly lower levels of p16ink4a in comparison to the control group (p=0.009). FISH analysis demonstrated that the overwhelming majority of repaired kidney tissue was mouse in origin. Rat PCs were only detected at a frequency of 0.02%. These data confirm that PCs have the ability to mitigate functional damage to kidney tissue following I/R injury. Kidneys of PC-treated animals showed evidence of improved function and reduced expression of damage markers. The PCs appear to act in a paracrine fashion, stimulating the host tissue to recover functionally, rather than by differentiating into renal cells. This study demonstrates that pancreatic-derived PCs from the adult rat can enable functional repair of renal damage in mice. It validates the use of PCs to regenerate damaged tissues and also offers a novel therapeutic intervention for repair of solid organ damage in situ.

• Item Type: Articles
• Additional Information: This is a copy of an article published in the Rejuvenation Research © 2013 copyright Mary Ann Liebert, Inc.; Rejuvenation Research is available online at: http://online.liebertpub.com.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McGlynn, Dr Liane and Davies, Dr Robert and MacDonald, Dr Alasdair and Shiels, Professor Paul
• Authors: McGlynn, L.M., Eller, K., MacDonald, A.I., MacIntyre, A., Russell, D., Koppelstaetter, C., Davies, R., and Shiels, P.G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Rejuvenation Research
• Publisher: Mary Ann Liebert, Inc.
• ISSN: 1549-1684
• ISSN (Online): 1557-8577
• Copyright Holders: Copyright © 2013 Mary Ann Liebert, Inc.
• First Published: First published in Rejuvenation Research 16(1)11-20
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher