Pigment epithelium-derived factor regulation of neuronal and stem cell fate

Pigment epithelium-derived factor (PEDF) is an endogenous human glycoprotein first identified as a neurotrophic factor in retinal pigmented epithelium cells. PEDF has since been shown to play a central role in mediating cellular protection against oxidative stress, by promoting cell survival, reducing inflammation, and inhibiting pathological angiogenesis in a range of cell types and tissues. PEDF is a well-established neurotrophic factor which supports neurogenesis and provides neuroprotection in response to cellular stress, with numerous studies demonstrating the ability of PEDF to promote neuronal survival and growth following injury. PEDF is an essential component of the stem cell microenvironment and bone extracellular matrix, where it regulates the differentiation of osteoblast precursor cells to promote normal bone development. Accumulating evidence indicates that PEDF maintains stem cell populations and promotes neuronal growth and bone formation by directing cell fate and regulating cell cycle progression. The ability of PEDF to promote neurogenesis, osteogenesis, and stemness indicates therapeutic potential in diseases characterised by tissue degeneration. In this review, we provide a current summary of the role of PEDF in regulating cellular survival and differentiation in bone, the central nervous system, and other stem cell niches, and highlight the emerging potential of PEDF as a regenerative therapeutic agent.