Characterization of ion currents of murine CD117pos stem cells in vitro and their modulation under AT2R stimulation. (24th May 2013)

• Record Type: Journal Article
• Authors: Ludwig, M.; Skorska, A.; Tölk, A.; Hopp, H.‐H.; Patejdl, R.; Li, J.; Steinhoff, G.; Noack, T.
• Is Part Of: Acta physiologica. Volume 208:Number 3(2013:Jul.)
• Page Start: 274
• Page End: 287
• Publication Date: 2013-05-24
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12115
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" id="apha12115-abs-0001"> <title>Abstract</title> <sec id="apha12115-sec-0001" sec-type="section"> <title>Aim</title> <p>Hematopoietic stem cells, especially CD117<sup>pos</sup> cells, have been found to possess a regenerative potential in various tissues, in particular cardiac muscle. However, the characterization of the relevant ion currents of stem cells prior to implantation lacks documentation. Activation of angiotensin II type 2 receptor (AT<sub>2</sub>R) can lead to further cell differentiation and receptor auto‐expression and might thus influence electrophysiological properties of CD117<sup>pos</sup> stem cells. This study was designed to functionally characterize membrane currents of CD117<sup>pos</sup> cells under normal and AT<sub>2</sub>R‐stimulated conditions.</p> </sec> <sec id="apha12115-sec-0002" sec-type="section"> <title>Methods</title> <p>CD117<sup>pos</sup> murine bone marrow stem cells were isolated with MACS technique and stimulated for the AT<sub>2</sub>R with angiotensin II and losartan for 3–5 days prior to patch‐clamp measurements. RT‐PCR was used to determine channel expression. Endothelial properties were analysed with immunocytochemistry and acLDL uptake assay.</p> </sec> <sec id="apha12115-sec-0003" sec-type="section"> <title>Results</title> <p>A well‐expressed inward rectifying current (I<sub>Kir</sub>) was identified in cultured CD117<sup>pos</sup> cells. Furthermore, a ZD 7288 (HCN channel blocker)‐sensitive current component was isolated. Voltage‐dependent potassium currents and chloride currents were less expressed. A small fraction of cells demonstrated voltage‐ and time‐dependent inward currents. In AT<sub>2</sub>R‐stimulated cells inward rectifying the hyperpolarization‐induced inward currents were slightly attenuated on the translational level but showed increased mRNA expression. Cultured CD117<sup>pos</sup> cells express CD31 and VEGFR‐2 and significantly increased the uptake of acLDL.</p> </sec> <sec id="apha12115-sec-0004" sec-type="section"> <title>Conclusions</title> <p>CD117<sup>pos</sup> cells do not have properties of action potential–generating cells and moderately change their excitability during AT<sub>2</sub>R stimulation. Electrophysiological and molecular properties of control and AT<sub>2</sub>R‐stimulated cells point to a differentiation to vascular endothelial cells. This could increase beneficial vascularization in injured tissues.</p> </sec> </abstract>