Myelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease
Luiza Stanaszek,
Malgorzata Majchrzak,
Katarzyna Drela,
Piotr Rogujski,
Joanna Sanford,
Michal Fiedorowicz,
Magdalena Gewartowska,
Malgorzata Frontczak-Baniewicz,
Piotr Walczak,
Barbara Lukomska,
Miroslaw Janowski
Affiliations
Luiza Stanaszek
NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
Malgorzata Majchrzak
NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
Katarzyna Drela
Medical Research Agency, 02-106 Warsaw, Poland
Piotr Rogujski
NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
Joanna Sanford
Vetregen Laboratory and Stem Cell Bank for Animals, 04-687 Warsaw, Poland
Michal Fiedorowicz
Small Animal Magnetic Resonance Imaging Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
Magdalena Gewartowska
Electron Microscopy Platform, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
Malgorzata Frontczak-Baniewicz
Electron Microscopy Platform, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
Piotr Walczak
Department of Diagnostic Radiology and Nuclear Medicine, Center for Advanced Imaging Research, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA
Barbara Lukomska
NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
Miroslaw Janowski
Department of Diagnostic Radiology and Nuclear Medicine, Center for Advanced Imaging Research, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA
Background: Dysfunction of glia contributes to the deterioration of the central nervous system in a wide array of neurological disorders, thus global replacement of glia is very attractive. Human glial-restricted precursors (hGRPs) transplanted intraventricularly into neonatal mice extensively migrated and rescued the lifespan in half of the studied mice, whereas mouse GRPs (mGRPs) presented no therapeutic benefit. We studied in the same experimental setting canine GRPs (cGRP) to determine whether their therapeutic potential falls between hGRPs and mGRPs. Additional motivation for the selection of cGRPs was a potential for use in veterinary medicine. Methods: cGRPs were extracted from the brain of dog fetuses. The cells were transplanted into the anterior or posterior aspect of the lateral ventricle (LV) of neonatal, immunodeficient, dysmyelinated mice (Mbpshi, Rag2 KO; shiv/rag2). Outcome measures included early cell biodistribution, animal survival and myelination assessed with MRI, immunohistochemistry and electron microscopy. Results: Grafting of cGRP into posterior LV significantly extended animal survival, whereas no benefit was observed after anterior LV transplantation. In contrast, myelination of the corpus callosum was more prominent in anteriorly transplanted animals. Conclusions: The extended survival of animals after transplantation of cGRPs could be explained by the vicinity of the transplant near the brain stem.
