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Ependymal Stem Cells

Drugging Resident Cellular Progenitors for Spinal Cord Injury Repair

Original article from STEM CELLS

“FM19G11 Favors Spinal Cord Injury Regeneration and Stem Cell Self-Renewal by Mitochondrial Uncoupling and Glucose Metabolism Induction”

Activation of resident adult stem/progenitor cells for the treatment of some disease/injury states is often seen as a viable alternative to the transplantation of embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC) derived cells. Ependymal stem progenitor cells (epSPCs) reside in the adult spinal cord and, upon transplantation, have been shown to rescue lost locomotor activity associated with spinal cord injury (SCI) (Moreno-Manzano et al 2009). Therefore, activation of resident epiSCs through pharmacological means may be a viable non-invasive therapeutic option for SCI.   Previous research has provided potential targets for therapeutic agents; mitochondrial bio-energetics have been identified as a potentially drugable target for SCI (Sullivan et al), with mitochondrial uncoupling a suggested  pharmacological therapy for acute SCI (Patel et al) or those patients with long term injury (Jin et al). Additionally, glucose uptake and ATP generated by glycolysis is abundant in stem cells, but not in differentiated cells, suggesting that modulation of glucose uptake and trafficking may also represent a target to activate adult stem cells. Now in a study published in Stem Cells, researchers from the laboratory of Victoria Moreno-Manzano at the CIPF, Valencia, Spain have shown that the chemical compound FM19G11, first identified as an inhibitor of HIFα protein expression and transcriptional activity under hypoxic conditions and which represses stemness-associated genes (Moreno-Manzano et al 2010), can modify the mitochondrial uncoupling process and induces glucose uptake by activation of AMPK (AMP-activated kinase) and AKT (or protein kinase B) signaling pathways in epSPCs. Excitingly, this is associated with an increase in the self-renewal of epSPC and the rescue of lost locomotor activity in rat SCI indicating this drugs potential usefulness for spinal cord disorders (Rodríguez-Jimnez et al).

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