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Davoli, K. A.

Publications and source records attributed to Davoli, K. A..

2 recordsLinked to original sources

Characterization of zebrafish nucleus pulposus in development and aging: A fish model for probing human intervertebral disc degeneration and regeneration

Intervertebral disc (IVD) degeneration (IDD) contributes to low back and neck pain. The nucleus pulposus (NP) of the IVD is usually degenerated first in age-related IDD. Addressing NP degeneration remains challenging due to insufficient understanding of its etiologies. Here, we characterize zebrafish IVD, particularly the NP, and note several characteristics that are common to or different from those of mammals. The adult zebrafish NP can be partitioned into three sections: the NP envelope with a monolayer of basal cells, the peripheral region with clustered vacuolated and non-vacuolated NP cells, and the central fibrotic region with low cellularity. With age, the percentage of vacuolated NP cells decreases, whereas that of non-vacuolated NP cells increases, as in mammals. However, a cluster of vacuolated cells persists in the NP periphery even in aged zebrafish. Notably, the ratio of the span of the fibrotic NP center to NP diameter remains largely constant at 50% regardless of age, suggesting that the zebrafish NP can better maintain its overall shape and structure, compared to mammalian NP. The fibrotic NP center and cell-populated NP periphery serve as internal controls to each other for studying NP maintenance and fibrosis. With external development, high fecundity, and great regenerative capabilities, zebrafish may be a unique NP model to complement mammalian models for studying how the NP degenerates and how the dormant capability of NP regeneration may be revitalized in humans.

developmental biology↗

Stem cell-free therapy for glaucoma to preserve vision

Glaucoma is the leading cause of irreversible blindness with trabecular meshwork (TM) dysfunction resulting in elevated intraocular pressure and retinal ganglion cell (RGC) damage leading to vision loss. In this study, we discovered that secretome, derived from human TM stem cells, via minimal invasive periocular injection, can reduce intraocular pressure, restore TM homeostasis, protect RGC, and restore RGC function in both steroid-induced and genetic myocilin mutant mouse models of glaucoma. The secretome upregulated the COX2-PGE2 axis via mitochondrial TMEM177 and led to activation of endogenous stem cells and TM regeneration. Inhibition of COX2 abolished the protective effect of secretome on TM cells. Secretome treatment also enhanced RGC survival and function. Proteomic analysis revealed that the secretome is enriched with proteins involved in extracellular matrix modulation leading to the remodeling of TM to restore homeostasis. This study highlights the feasibility of stem cell-free therapy for glaucoma with minimal invasive administration and the involvement of multiple novel pathways for a cumulative regenerative effect on the TM to protect RGC. Brief summaryThis study describes a cell-free treatment using stem cell secretome in two animal models of glaucoma and explores the potential mechanisms

cell biology↗