Immuno-EM shows axon sorting, ensheathment, and myelination are improved in stem cell-treated mutant sciatic nerves.

Members of the Strickland Laboratory are investigating the potential of stem cells to rescue peripheral nerve defects. Previous results show that murine Adipose Derived Stem Cells (mADSCs) can rescue sciatic nerve dysfunction in young adult laminin-deficient mice. Electrophysiology studies of laminin-deficient sciatic nerves reveals impaired nerve conduction velocity (NCV), maximum amplitude of compound motor action potential (CMAP), and the minimum current needed to induce muscle twitch (MCST) in comparison to control animals. After treatment with mADSCs, NCV is returned to that of wild type animals, and there is significant improvement of the CMAP and MCST. Rescue is dependent on mADSC production of laminin, and is in part due to stimulation of endogenous mutant Schwann cells to sort, ensheath, and myelinate axons. These results indicate that developmentally-arrested mutant Schwann cells retain the potential to respond to normal developmental cues and become mature myelinating glia.

Karen Carlson, Anita Ramnarain, and Chia Chan of the Strickland Lab are currently investigating the molecular and cellular basis for this rescue as well as evaluating the potential for other neural crest-derived stem cells to rescue laminin-deficient peripheral nerve dysfunction. In order to answer these questions, it is necessary to develop new tools that facilitate comprehensive characterization of the cellular response to introduction of stem cells. Therefore, we are also collaborating with Dr. Nathaniel Heintz at The Rockefeller University to develop a mouse line in which the mRNA translation profile of Schwann cells can be determined. These mice will then be used to uncover new proteins critical to Schwann cell response to stem cell treatment. In addition, these mice will allow systematic investigation into Schwann cell response to peripheral nerve injury such as sciatic nerve crush or neurotoxin administration.

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