Bone marrow-derived cells and their conditioned medium induce microvascular repair in uremic rats by stimulation of endogenous repair mechanisms

The reduced number of circulating stem/progenitor cells that is found in chronic kidney disease (CKD) patients may contribute to impaired angiogenic repair and decreased capillary density in the heart. Cell therapy with bone marrow-derived cells (BMDCs) has been shown to induce positive effects on t...

Authors: Golle, Lina
Gerth, Hans Ulrich
Beul, Katrin
Heitplatz, Barbara
Barth, Peter
Fobker, Manfred
Pavenstädt, Hermann
Di Marco, Giovana S.
Brand, Marcus
Division/Institute:FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2017
Date of publication on miami:26.10.2018
Modification date:16.04.2019
Edition statement:[Electronic ed.]
Source:Scientific Reports 7 (2017) 9444, 1-15
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Funding:Finanziert durch den Open-Access-Publikationsfonds 2017 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
URN:urn:nbn:de:hbz:6-17109648293
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-17109648293
Other Identifiers:DOI: 10.1038/s41598-017-09883-x
Digital documents:s41598-017-09883-x.pdf

The reduced number of circulating stem/progenitor cells that is found in chronic kidney disease (CKD) patients may contribute to impaired angiogenic repair and decreased capillary density in the heart. Cell therapy with bone marrow-derived cells (BMDCs) has been shown to induce positive effects on the microvasculature and cardiac function, most likely due to secretion of growth factors and cytokines, all of which are present in the conditioned medium (CM); however, this is controversial. Here we showed that treatment with BMDC or CM restored vascular density and decreased the extent of fibrosis in a rat model of CKD, the 5/6 nephrectomy. Engraftment and differentiation of exogenous BMDCs could not be detected. Yet CM led to the mobilization and infiltration of endogenous circulating cells into the heart. Cell recruitment was facilitated by the local expression of pro-inflammatory factors such as the macrophage chemoattractant protein-1, interleukin-6, and endothelial adhesion molecules. Consistently, in vitro assays showed that CM increased endothelial adhesiveness to circulating cells by upregulating the expression of adhesion molecules, and stimulated angiogenesis/endothelial tube formation. Overall, our results suggest that both treatments exert vasculoprotective effects on the heart of uremic rats by stimulating endogenous repair mechanisms.