Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury

Abstract

Optic neuropathies are the leading cause of irreversible blindness and visual impairment in the developed countries, affecting more than 80 million people worldwide. While most optic neuropathies have no effective treatment, there is intensive research on retinal ganglion cell (RGC) protection and axon regeneration. We previously demonstrated potential of human periodontal ligament-derived stem cells (PDLSCs) for retinal cell replacement. Here, we report the neuroprotective effect of human PDLSCs to ameliorate RGC degeneration and promote axonal regeneration after optic nerve crush (ONC) injury. Human PDLSCs were intravitreally injected into the vitreous chamber of adult Fischer rats after ONC in vivo as well as cocultured with retinal explants in vitro. Human PDLSCs survived in the vitreous chamber and were maintained on the RGC layer even at 3 weeks after ONC. Immunofluorescence analysis of βIII-tubulin and Gap43 showed that the numbers of surviving RGCs and regenerating axons were significantly increased in the rats with human PDLSC transplantation. In vitro coculture experiments confirmed that PDLSCs enhanced RGC survival and neurite regeneration in retinal explants without inducing inflammatory responses. Direct cell-cell interaction and elevated brain-derived neurotrophic factor secretion, but not promoting endogenous progenitor cell regeneration, were the RGC protective mechanisms of human PDLSCs. In summary, our results revealed the neuroprotective role of human PDLSCs by strongly promoting RGC survival and axonal regeneration both in vivo and in vitro, indicating a therapeutic potential for RGC protection against optic neuropathies. Stem Cells 2018;36:844-855.

Expression of SARS-CoV-2 receptor ACE2 and TMPRSS2 in human primary conjunctival and pterygium cell lines and in mouse cornea

“…Human ocular cell lines, including retinal pigment epithelial (RPE) cells ARPE-19 (catalogue number: CRL-2302, American Type Culture Collection (ATCC), Manassas, VA) [11,12], lens epithelial cells B3 (catalogue number: CRL-11421, ATCC) [13], primary trabecular meshwork (TM) cells [14], and retinoblastoma cells Y79 (catalogue number: HTB-18, ATCC) [15], have been previously established. We also collected human mesenchymal stem cells (MSCs) from different sources, including bone marrow-derived MSCs (BM-MSCs; catalogue number: 7500; ScienceCell Research Laboratories, Carlsbad, CA) [16], adipose-derived stem cells (ASCs) [17], and periodontal ligament-derived stem cells (PDLSCs) [18,19]. Other human tissue cell lines, such as human umbilical vein endothelial cells (HUVEC; catalogue number: CRL-1730, ATCC), lung epithelial carcinoma cells A549 (catalogue number: CCL-185, ATCC), liver hepatocellular carcinoma cells HepG2 (catalogue number: HB-8065, ATCC) and epidermal keratinocytes HaCaT (catalogue number: T0020001, AddexBio, San Diego, CA), were also investigated in this study.…”

Viability of Mouse Retinal Explant Cultures Assessed by Preservation of Functionality and Morphology

“…Organotypic retinal explant cultures have been used to study retinal development, [14][15][16] retinal diseases and injuries, [17][18][19][20][21][22][23][24][25][26] drug screening, 3,[27][28][29][30][31][32][33] and retinal stem cell therapies. 8,34,35 The culture systems also have high potential outside these fields, and they could be beneficial for completely new fields, including prion research and, specifically, prion organo-typic slice culture assays. 36 Rodent retinae are most commonly used in explant cultures due to their flexibility in gene manipulation.…”

Oral Mesenchymal Stem/Progenitor Cells: The Immunomodulatory Masters

“…Optic neuropathies, the leading cause of irreversible blindness and visual impairment, which result from trauma injury, glaucoma, inflammation, ischemia, or tumor compression, are characterized by the degeneration of retinal ganglion cells (RGCs) and their axons. Intravitreal injection of PDLSCs into the rat vitreous chamber in the optic nerve injury model could promote the survival and neurite regeneration of RGCs by increasing brainderived neurotrophic factor secretion in a direct cell-cellcontact manner [132].…”