Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model

Human pluripotent stem cell-derived neural progenitor cells (NPCs) have the potential to recover from nerve injury. We previously reported that human placenta-derived mesenchymal stem cells (PSCs) have neuroprotective effects. To evaluate the potential benefit of NPCs, we compared them to PSCs using...

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Autores principales:	Mira Park, Hyun-Mun Kim, Hyun-Ah Shin, Seung-Hyun Lee, Dong-Youn Hwang, Helen Lew
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	human pluripotent stem cell-derived neuronal progenital cells (NPCs) human placenta-derived mesenchymal stem cells (PSCs) optic nerve compression model neuroprotection ganglion cell survival axon recovery Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/67733c61b50b49e09bd09a5176446b05
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spelling	oai:doaj.org-article:67733c61b50b49e09bd09a5176446b052021-11-25T17:57:32ZHuman Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model10.3390/ijms2222125291422-00671661-6596https://doaj.org/article/67733c61b50b49e09bd09a5176446b052021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12529https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Human pluripotent stem cell-derived neural progenitor cells (NPCs) have the potential to recover from nerve injury. We previously reported that human placenta-derived mesenchymal stem cells (PSCs) have neuroprotective effects. To evaluate the potential benefit of NPCs, we compared them to PSCs using R28 cells under hypoxic conditions and a rat model of optic nerve injury. NPCs and PSCs (2 × 106 cells) were injected into the subtenon space. After 1, 2, and 4 weeks, we examined changes in target proteins in the retina and optic nerve. NPCs significantly induced vascular endothelial growth factor (Vegf) compared to age-matched shams and PSC groups at 2 weeks; they also induced neurofilaments in the retina compared to the sham group at 4 weeks. In addition, the expression of brain-derived neurotrophic factor (Bdnf) was high in the retina in the NPC group at 2 weeks, while expression in the optic nerve was high in both the NPC and PSC groups. The low expression of ionized calcium-binding adapter molecule 1 (Iba1) in the retina had recovered at 2 weeks after NPC injection and at 4 weeks after PSC injection. The expression of the inflammatory protein NLR family, pyrin domain containing 3 (Nlrp3) was significantly reduced at 1 week, and that of tumor necrosis factor-α (Tnf-α) in the optic nerves of the NPC group was lower at 2 weeks. Regarding retinal ganglion cells, the expressions of Brn3a and Tuj1 in the retina were enhanced in the NPC group compared to sham controls at 4 weeks. NPC injections increased Gap43 expression from 2 weeks and reduced Iba1 expression in the optic nerves during the recovery period. In addition, R28 cells exposed to hypoxic conditions showed increased cell survival when cocultured with NPCs compared to PSCs. Both Wnt/β-catenin signaling and increased Nf-ĸb could contribute to the rescue of damaged retinal ganglion cells via upregulation of neuroprotective factors, microglial engagement, and anti-inflammatory regulation by NPCs. This study suggests that NPCs could be useful for the cellular treatment of various optic neuropathies, together with cell therapy using mesenchymal stem cells.Mira ParkHyun-Mun KimHyun-Ah ShinSeung-Hyun LeeDong-Youn HwangHelen LewMDPI AGarticlehuman pluripotent stem cell-derived neuronal progenital cells (NPCs)human placenta-derived mesenchymal stem cells (PSCs)optic nerve compression modelneuroprotectionganglion cell survivalaxon recoveryBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12529, p 12529 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human pluripotent stem cell-derived neuronal progenital cells (NPCs) human placenta-derived mesenchymal stem cells (PSCs) optic nerve compression model neuroprotection ganglion cell survival axon recovery Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	human pluripotent stem cell-derived neuronal progenital cells (NPCs) human placenta-derived mesenchymal stem cells (PSCs) optic nerve compression model neuroprotection ganglion cell survival axon recovery Biology (General) QH301-705.5 Chemistry QD1-999 Mira Park Hyun-Mun Kim Hyun-Ah Shin Seung-Hyun Lee Dong-Youn Hwang Helen Lew Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model
description	Human pluripotent stem cell-derived neural progenitor cells (NPCs) have the potential to recover from nerve injury. We previously reported that human placenta-derived mesenchymal stem cells (PSCs) have neuroprotective effects. To evaluate the potential benefit of NPCs, we compared them to PSCs using R28 cells under hypoxic conditions and a rat model of optic nerve injury. NPCs and PSCs (2 × 106 cells) were injected into the subtenon space. After 1, 2, and 4 weeks, we examined changes in target proteins in the retina and optic nerve. NPCs significantly induced vascular endothelial growth factor (Vegf) compared to age-matched shams and PSC groups at 2 weeks; they also induced neurofilaments in the retina compared to the sham group at 4 weeks. In addition, the expression of brain-derived neurotrophic factor (Bdnf) was high in the retina in the NPC group at 2 weeks, while expression in the optic nerve was high in both the NPC and PSC groups. The low expression of ionized calcium-binding adapter molecule 1 (Iba1) in the retina had recovered at 2 weeks after NPC injection and at 4 weeks after PSC injection. The expression of the inflammatory protein NLR family, pyrin domain containing 3 (Nlrp3) was significantly reduced at 1 week, and that of tumor necrosis factor-α (Tnf-α) in the optic nerves of the NPC group was lower at 2 weeks. Regarding retinal ganglion cells, the expressions of Brn3a and Tuj1 in the retina were enhanced in the NPC group compared to sham controls at 4 weeks. NPC injections increased Gap43 expression from 2 weeks and reduced Iba1 expression in the optic nerves during the recovery period. In addition, R28 cells exposed to hypoxic conditions showed increased cell survival when cocultured with NPCs compared to PSCs. Both Wnt/β-catenin signaling and increased Nf-ĸb could contribute to the rescue of damaged retinal ganglion cells via upregulation of neuroprotective factors, microglial engagement, and anti-inflammatory regulation by NPCs. This study suggests that NPCs could be useful for the cellular treatment of various optic neuropathies, together with cell therapy using mesenchymal stem cells.
format	article
author	Mira Park Hyun-Mun Kim Hyun-Ah Shin Seung-Hyun Lee Dong-Youn Hwang Helen Lew
author_facet	Mira Park Hyun-Mun Kim Hyun-Ah Shin Seung-Hyun Lee Dong-Youn Hwang Helen Lew
author_sort	Mira Park
title	Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model
title_short	Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model
title_full	Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model
title_fullStr	Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model
title_full_unstemmed	Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model
title_sort	human pluripotent stem cell-derived neural progenitor cells promote retinal ganglion cell survival and axon recovery in an optic nerve compression animal model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/67733c61b50b49e09bd09a5176446b05
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Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model

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