title: PEDF & stem cells: niche vs. nurture.
abstract: Anti-angiogenic pigment epithelium-derived factor (PEDF) is a multifunctional 50kD secreted glycoprotein emerging as a key factor in stem cell renewal. Characteristics of the stem cell niche can be highly dependent on location, access to the vasculature, oxygen tension and neighboring cells. In the neural stem cell (NSC) niche, specifically the subventricular zone, PEDF actively participates in the self renewal process and promotes stemness by upregulating Notch signaling effectors Hes1 and Hes5. The local vascular endothelial cells and ependymal cells are the likely sources of PEDF for the NSC while mesenchymal and retinal stem cells can actually produce PEDF. The opposing actions of PEDF and VEGF on various cells are recapitulated in the NSC niche. Intraventricular injection of PEDF promotes stem cell renewal, while injection of VEGF prompts differentiation and neurogenesis in the subventricular zone. Enhancing the expression of PEDF in stem cells has promising therapeutic implications. Bone marrow mesenchymal stem cells overexpressing PEDF effectively inhibited pathologic angiogenesis in the murine eye and these same cells suppressed hepatocellular carcinoma growth. As a protein with bioactivities in nearly all normal organ systems, it is likely that PEDF will continue to gain visibility as an essential component in the development and delivery of novel stem cell-based therapies to combat disease.
authors.forename: Philip
authors.initials: P
authors.lastname: Fitchev
authors.forename: Chuhan
authors.initials: C
authors.lastname: Chung
authors.forename: Beth A
authors.initials: BA
authors.lastname: Plunkett
authors.forename: Charles B
authors.initials: CB
authors.lastname: Brendler
authors.affiliation: NorthShore Univ. Research Institute, Affiliate of University of Chicago, 1001 University Place, 3rd Floor, Evanston, IL 60201, USA. scrawford@northwestern.edu.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Crawford
mesh_terms: D000818:Animals; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor