Neuroprotection of host cells by human central nervous system stem cells in a mouse model of infantile neuronal ceroid lipofuscinosis

Cell Stem Cell. 2009 Sep 4;5(3):310-9. doi: 10.1016/j.stem.2009.05.022.


Infantile neuronal ceroid lipofuscinosis (INCL) is a fatal neurodegenerative disease caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). Ppt1 knockout mice display hallmarks of INCL and mimic the human pathology: accumulation of lipofuscin, degeneration of CNS neurons, and a shortened life span. Purified non-genetically modified human CNS stem cells, grown as neurospheres (hCNS-SCns), were transplanted into the brains of immunodeficient Ppt1(-/)(-) mice where they engrafted robustly, migrated extensively, and produced sufficient levels of PPT1 to alter host neuropathology. Grafted mice displayed reduced autofluorescent lipofuscin, significant neuroprotection of host hippocampal and cortical neurons, and delayed loss of motor coordination. Early intervention with cellular transplants of hCNS-SCns into the brains of INCL patients may supply a continuous and long-lasting source of the missing PPT1 and provide some therapeutic benefit through protection of endogenous neurons. These data provide the experimental basis for human clinical trials with these banked hCNS-SCns.

MeSH terms

  • Animals
  • Brain / enzymology
  • Brain / pathology
  • Cell Differentiation
  • Cell Movement
  • Cell Survival
  • Central Nervous System / cytology*
  • Cytoprotection*
  • Disease Models, Animal
  • Endocytosis
  • Fibroblasts / cytology
  • Fibroblasts / enzymology
  • Fluorescence
  • Humans
  • Inflammation / complications
  • Inflammation / pathology
  • Intracellular Space / enzymology
  • Lipofuscin / metabolism
  • Mice
  • Motor Activity
  • Mutation / genetics
  • Nerve Degeneration / complications
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Neuronal Ceroid-Lipofuscinoses / complications
  • Neuronal Ceroid-Lipofuscinoses / pathology*
  • Neuronal Ceroid-Lipofuscinoses / physiopathology
  • Neuronal Ceroid-Lipofuscinoses / therapy*
  • Neurons / cytology*
  • Neurons / enzymology
  • Receptor, IGF Type 2 / metabolism
  • Stem Cell Transplantation
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Thiolester Hydrolases / deficiency
  • Thiolester Hydrolases / metabolism


  • Lipofuscin
  • Receptor, IGF Type 2
  • Thiolester Hydrolases
  • palmitoyl-protein thioesterase