title: Human glial progenitor engraftment and gene expression is independent of the ALS environment.
abstract: Although Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, basic research studies have highlighted that astrocytes contribute to the disease process. Therefore, strategies which replace the diseased astrocyte population with healthy astrocytes may protect against motor neuron degeneration. Our studies have sought to evaluate astrocyte replacement using glial-restricted progenitors (GRPs), which are lineage-restricted precursors capable of differentiating into astrocytes after transplantation. The goal of our current study was to evaluate how transplantation to the diseased ALS spinal cord versus a healthy, wild-type spinal cord may affect human GRP engraftment and selected gene expression. Human GRPs were transplanted into the spinal cord of either an ALS mouse model or wild-type littermate mice. Mice were sacrificed for analysis at either the onset of disease course or at the endstage of disease. The transplanted GRPs were analyzed by immunohistochemistry and NanoString gene profiling which showed no gross differences in the engraftment or gene expression of the cells. Our data indicate that human glial progenitor engraftment and gene expression is independent of the neurodegenerative ALS spinal cord environment. These findings are of interest given that human GRPs are currently in clinical development for spinal cord transplantation into ALS patients.
authors.affiliation: Department of Neurology, Johns Hopkins University, 250.10 Rangos Building, 855 North Wolfe St., Baltimore, MD 21205, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Haidet-Phillips
authors.affiliation: Department of Neurology, Johns Hopkins University, 250.10 Rangos Building, 855 North Wolfe St., Baltimore, MD 21205, USA.
authors.forename: Arpitha
authors.initials: A
authors.lastname: Doreswamy
authors.affiliation: Department of Neurology, Johns Hopkins University, 250.10 Rangos Building, 855 North Wolfe St., Baltimore, MD 21205, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Gross
authors.affiliation: Department of Neurology, Johns Hopkins University, 250.10 Rangos Building, 855 North Wolfe St., Baltimore, MD 21205, USA.
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Tang
authors.affiliation: Q Therapeutics, Inc., 615 Arapeen Drive, Suite 102, Salt Lake City, UT 84108, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Campanelli
authors.affiliation: Department of Neurology, Johns Hopkins University, 250.10 Rangos Building, 855 North Wolfe St., Baltimore, MD 21205, USA. Electronic address: nmaragak@jhmi.edu.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Maragakis
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002102:Cadaver; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D005333:Fetus; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology* / Q000637:transplantation*; D000076104:Oligodendrocyte Transcription Factor 2; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D034961:Antigens, Nuclear; D051792:Basic Helix-Loop-Helix Proteins; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D013482:Superoxide Dismutase; C512773:Olig2 protein, mouse; C109415:SOD1 G93A protein
keywords: Astrocyte; Neurodegeneration; Stem cells; Transplantation