Research: human stem cells in mice

Epub ahead of print: Kim et al. ICV-transplanted human glial precursor cells are short-lived yet exert immunomodulatory effects in mice with EAE.Glia. 2012 Apr 12. doi: 10.1002/glia.22339.

Background: Human glial precursor cells (hGPs) have potential for remyelinating lesions and are an attractive cell source for cell therapy of MS. To investigate whether transplanted hGPs can affect the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, these investigators evaluated the therapeutic effects of transplanted hGPs together with the fate of these cells using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI).

Bioluminescence imaging (BLI) is a technique to allow you to see cells inside the body of the mice; they give off light.

Methods: At 14 days post-EAE induction, mice (n = 19) were intracerebroventricularly (ICV) injected (a big term for an injection into the fluid spaces or ventricle of the brain) with 5 × 10(5) hGPs that were magnetically labeled with superparamagnetic iron oxide (SPIO) particles as MR contrast agent and transduced with firefly luciferase for BLI of cell survival. Control mice (n = 18) received phosphate buffered saline (PBS) vehicle only.

Results: The severity of EAE clinical disability in the hGP-transplanted group was significantly suppressed (P < 0.05) with concomitant inhibition of ConA and MOG-specific T cell proliferation in the spleen (markers of immune activation were suppressed). Astrogliosis (scare tissue) was reduced and a lower activity of macrophages and/or microglia was observed in the spinal cord (P < 0.05) (these are the scavenger cells). On MRI, SPIO signal was detected within the lateral ventricle from 1 day post-transplantation and remained there for up to 34 days. BLI indicated that most cells did not survive beyond 5-10 days, consistent with the lack of detectable migration into the brain parenchyma and the histological presence of an abundance of apoptotic cells (dying cells). Transplanted hGPs could not be detected in the spleen.

Conclusion: The investigators concluded that ICV transplantation of short-lived hGPs can have a remote therapeutic effect through immunomodulation from within the ventricle, without cells directly participating in remyelination.



This shows that such cells have an immune modulating protential, which is known already and better results can be achieved using current immunosuppressive agents. Because they are human cells put into mice they quickly get rejected within 5 days which is too short to determine whether they could actually produce repair. That the signal could be found is reflective of the SPIO (iron particles) to be ingested as as dead cells are digested.

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