title: Extracellular matrix produced by bone marrow stromal cells and by their derivative, SB623 cells, supports neural cell growth.
abstract: Several studies have shown the benefits of transplanting bone marrow-derived multipotent mesenchymal stromal cells (MSC) into neurodegenerative lesions of the central nervous system, despite a low engraftment rate and the poor persistence of grafts. It is known that the extracellular matrix (ECM) modulates neuritogenesis and glial growth, but little is known about effects of MSC-derived ECM on neural cells. In this study, we demonstrate in vitro that the ECM produced by MSC can support neural cell attachment and growth. We also compare the neurosupportive properties of MSC to the MSC derivative, SB623 cells, which is being developed as a cell therapy for stroke. Embryonic rat brain cortical cells cultured for 3 weeks on human MSC- and SB623 cell-derived ECM exhibit about a 1.5 and 3 times higher metabolic activity, respectively, compared with the cultures grown on poly-D-lysine (PDL), although the initial neural cell adhesion to cell-derived ECM and PDL is similar. The MSC- and SB623 cell-derived ECM protects neural cells from nutrient and growth factor deprivation. Under the conditions used, only neurons grow on PDL. In contrast, both MSC- and SB623 cell-derived ECMs support the growth of neurons, astrocytes, and oligodendrocytes, as demonstrated by immunostaining. Morphologically, neurons on cell-derived ECM form more complex and extended neurite networks than those cultured on PDL. Together, these data indicate that the beneficial effect of MSC and SB623 cells in neurotransplantation could be explained in part by the neurosupportive properties of the ECM produced by these cells.
authors.affiliation: SanBio, Inc., Mountain View, California 94041, USA. irina.aizman@san-bio.com
authors.forename: Irina
authors.initials: I
authors.lastname: Aizman
authors.forename: Ciara C
authors.initials: CC
authors.lastname: Tate
authors.forename: Michael
authors.initials: M
authors.lastname: McGrogan
authors.forename: Casey C
authors.initials: CC
authors.lastname: Case
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000378:metabolism; D002448:Cell Adhesion; D049109:Cell Proliferation; D002470:Cell Survival; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D039902:Multipotent Stem Cells / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology; D051381:Rats; D051881:Receptor, Notch1 / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism; D014162:Transfection
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1