title: Maintenance of a functional hematopoietic stem cell niche through galactocerebrosidase and other enzymes.
abstract: OBJECTIVE
  The maintenance of a functional hematopoietic niche is critical for modulating the fate of hematopoietic stem cells (HSCs). Several enzymes were described as essential for guaranteeing niche functionality. This review summarizes the recent findings about the role of galactocerebrosidase and other enzymes involved in the maintenance of a functional HSC niche.
  
  
  RESULTS
  The essential role of enzymes actively involved in the maintenance of the bone marrow microenvironment, in bone remodeling, in regulating the sympathetic innervation of the niche, and in the production and relative balance of sphingolipids active in the niche has been recently highlighted. Enzymes involved in bone remodeling modify the cell-to-cell interaction between osteoblasts and HSCs. Heparanase, neutrophil elastase, and alpha-iduronidase affect the bioavailability of key cytokines and ligands within the extracellular matrix of the niche. Moreover, galactosyltransferase and galactocerebrosidase affect the function of the sympathetic nervous system and/or the balance of bioactive sphingolipids, thus influencing the SDF-1/CXCR4 axis and the proliferation of HSCs.
  
  
  CONCLUSIONS
  Here, we discuss the role of different enzymes directly or indirectly influencing the niche microenvironment, and we provide a comprehensive picture of their cooperative role, together with receptors, soluble factors, and the extracellular matrix, in maintaining a functional hematopoietic niche.
authors.affiliation: Division of Regenerative Medicine and Stem Cells, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Visigalli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Biffi
mesh_terms: D000818:Animals; D005698:Galactosylceramidase / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D051379:Mice; D055153:Stem Cell Niche / Q000166:cytology / Q000201:enzymology*
chemical_list: D005698:Galactosylceramidase