Neural precursor cells (NPCs) offer a promising approach for treating demyelinating diseases. However, the cellular dynamics that underlie transplanted NPC-mediated remyelination have not been described. Using two-photon imaging of a newly developed ventral spinal cord preparation and a viral model of demyelination, we describe the motility and intercellular interactions of transplanted mouse NPCs expressing green fluorescent protein (GFP) with damaged axons expressing yellow fluorescent protein (YFP). Our findings reveal focal axonal degeneration that occurs in the ventral side of the spinal cord within 1 wk following intracranial instillation with the neurotropic JHM strain of mouse hepatitis virus (JHMV). Axonal damage precedes extensive demyelination (So the nerve damage is first and demyelination is second. In MS we think it is the other way round or do we because this does not happen in mice can we rewrite history so it fits) and is characterized by swelling along the length of the axon, loss of YFP signal, and transected appearance. NPCs engrafted into spinal cords of JHMV-infected mice exhibited diminished migration velocities (slow speed of movement) and increased proliferation compared with transplanted cells in noniinfected mice. NPCs preferentially accumulated within areas of axonal damage, initiated direct contact with axons, and subsequently expressed the myelin proteolipid protein gene, initiating remyelination. These findings indicate that NPCs transplanted into an inflammatory demyelinating microenvironment participate directly in therapeutic outcome through the wrapping of myelin around damaged neurons.
#MSResearch Viewing #Stem cells remyelinate
Greenberg ML, Weinger JG, Matheu MP, Carbajal KS, Parker I, Macklin WB, Lane TE, Cahalan MD. Two-photon imaging of remyelination of spinal cord axons by engrafted neural precursor cells in a viral model of multiple sclerosis. Proc Natl Acad Sci U S A. 2014 May 19. pii: 201406658. [Epub ahead of print]
We have recently heard how neural stem cells help crippled mice to walk (click here), now we see that they can remyelinate