Abstract
The voltage-gated proton channel Hv1 is widely expressed, among others, in immune and cancer cells, it provides an efficient cytosolic H+extrusion mechanism and regulates vital functions such as oxidative burst, migration and proliferation. Here we demonstrate the presence of human Hv1 (hHv1) in the placenta/chorion-derived mesenchymal stem cells (cMSCs) using RT-PCR. The voltage- and pH-dependent gating of the current is similar to that of hHv1 expressed in cell lines and that the current is blocked by 5-chloro-2-guanidinobenzimidazole (ClGBI) and activated by arachidonic acid (AA). Inhibition of hHv1 by ClGBI significantly decreases mineral matrix production of cMSCs induced by conditions mimicking physiological or pathological (inorganic phosphate, Pi) induction of osteogenesis. Wound healing assay and single cell motility analysis show that ClGBI significantly inhibits the migration of cMSCs. Thus, seminal functions of cMSCs are modulated by hHv1 which makes this channel as an attractive target for controlling advantages/disadvantages of MSCs therapy.
Highlights
Mesenchymal stem cells (MSCs) are multipotent cells with intensive proliferative capacity and ability to differentiate into various cell types[1,2]
We demonstrated the expression of Hv1 mRNA transcripts in chorion-derived mesenchymal stem cells (cMSCs) using RT-PCR
We carried out this analysis with cMSCs isolated from two other placenta donors as well (Supplementary Fig. S1), our results were the same in all placentas examined
Summary
Mesenchymal stem cells (MSCs) are multipotent cells with intensive proliferative capacity and ability to differentiate into various cell types (osteoblasts, chondroblasts, myocytes, adipocytes etc.)[1,2]. Systemic delivery is preferred for the clinical applications which requires the homing and migration of MSCs to the target tissue. Voltage-gated proton channels have characteristic biophysical properties, e.g., they are highly selective for protons and the channels have extremely low single-channel conductance[19] Their gating is voltage-and pH dependent: changing of the intra- or extracellular (pHi or pHo, respectively) pH by one unit shifts the voltage-dependence of gating by 40 mV34. We measured the native proton current in cMSCs using the whole-cell patch-clamp technique and found that its biophysical and pharmacological characteristics (including pH- and voltage-dependence, ClGBI sensitivity, activation by AA) were consistent with the properties of the Hv1 channel. We propose that hHv1 might be a new target or control point in the regulation of therapeutic application of MSCs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
