Abstract

PHARMACOLOGICAL BLOCKING OF CHLORIDE CHANNELS MODULATES THE CELL CYCLE AND PROLIFERATION OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS

Gisely J. B. Albertim, Wyndly D. C. Gaiao, Marcia. B. Silva, Paulo E. C. Filho, Adriana Fontes, Reginaldo P. Silva, Valeria R. A. Pereira, Darlene P. Bezerra, Paloma L. Medeiros, Juliana P. Aguiar and Claudio G. Rodrigues*

ABSTRACT

The human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) are a promising source for regenerative medicine and tissue engineering. The high risk of malignancy is a limiting factor for their clinical use. Ion channels play an important role in cellular proliferation of many cell types, but the function of chloride channels (ClCs) in hWJ-MSCs remain unclear. Here we report the influence of 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) — pharmacological agent that acts by blocking the chloride channels — on the proliferation, viability, regulation of volume and cell cycle of hWJ-MSCs. We show that NPPB suppresses the regulatory volume decrease of isolated hWJ-MSCs under hypo-osmotic conditions. In addition, NPPB decreasing the proliferation of hWJ-MSCs, but does not alter its viability and this is because the NPPB promotes the accumulation of these cells in the G0/G1 phase, thus modulating the progression of the cell cycle. hWJ-MSCs only remain in a steady state. NPPB effect on cell cycle of hWJ-MSCs may be associated with the dysregulation of cell volume homeostasis. Therefore, pharmacological control of ClCs has identified as an important regulator of the hWJ-MSCs proliferation. In conclusion, our results clearly indicate that pharmacological agents that blocking the chloride channels cause the suppression of the regulatory volume decrease process, consequently modulating the cycle of human Wharton's jelly-derived mesenchymal stem cells, therefore, these blockers should be considered in the strategic planning for cell therapy and tissue engineering based on these cells.

Keywords: Chloride Channels, Channels Blocker, Proliferation, Stem cells, Viability.