Hypoxia-Preconditioned Placenta-Derived Mesenchymal Stem Cells Rescue Optic Nerve Axons Via Differential Roles of Vascular Endothelial Growth Factor in an Optic Nerve Compression Animal Model

Kwon, Heejung; Park, Soo‐Jin; Nepali, Sarmila; Lew, Helen

doi:10.1007/s12035-020-01965-8

Cited by 9 publications

(26 citation statements)

References 42 publications

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“…They enhanced the neuroprotective and neurorecovery abilities of in vitro models [29]. UBA2 expression is increased in a time-dependent manner in response to hypoxia, and is upregulated in the exosome [1]. Upregulation of Hif-1a/Vegf in MSCs by hypoxic preconditioning has also been reported [1].…”

Section: Discussionmentioning

confidence: 94%

“…In addition, they are immune-privileged because they express low levels of HLA class I antigens and do not present, or present very low levels of, CD80, CD86, CD40, and HLA class II antigens. Furthermore, other unique features such as easy separation, rapid growth after a short period of dormancy, and exemption from ethical issues make MSCs useful for cell therapy [1]. However, NPCs were derived from various conditions and chemical induction in many experiments [26].…”

Section: Discussionmentioning

confidence: 99%

“…Because there is no effective therapy for irreversible damage to the optic nerve, many studies have attempted to improve the essential regenerative capacity of retinal ganglion cells (RGCs) [1]. Macrophage-activating factors and zymosan promote axon regrowth after optic nerve damage [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have also identified the therapeutic effects of MSCs in ischemic models [18][19][20]. In addition to MSCs derived from bone marrow, those derived from human umbilical cord blood, dental pulp, and placenta show therapeutic effects in terms of generative induction and axonal growth of damaged optic nerves [1,21].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, regulation of the NF-κb pathway plays an important role in the regulation of target proteins in PSCs [23]. Another study demonstrated the possibility of using hypoxia-preconditioned PSCs (HPPCs) in cell therapy for optic nerve damage by examining the effects of regenerated nerves from HPPCs on R28 cells and in an animal model of optic nerve damage [1].…”

Section: Introductionmentioning

confidence: 99%

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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

Park

Kim

Shin

et al. 2021

IJMS

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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.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Park

Kim

Shin

et al. 2021

IJMS

Self Cite

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Mesenchymal stem cells for repairing glaucomatous optic nerve

Hu,

Chen,

et al. 2024

Int J Ophthalmol

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Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells (RGCs) and axons. Currently, there is no effective method to address the cause of RGCs degeneration. However, studies on neuroprotective strategies for optic neuropathy have increased in recent years. Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy. Regenerative medicine research into the repair of optic nerve damage using stem cells has received considerable attention. Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGC-friendly microenvironments through paracrine effects. This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury, raising the controversies and unresolved issues surrounding the future of stem cells.

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Unveiling Neuroprotection and Regeneration Mechanisms in Optic Nerve Injury: Insight from Neural Progenitor Cell Therapy with Focus on Vps35 and Syntaxin12

Shin,

Park,

Lee

et al. 2023

Preprint

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Axonal degeneration resulting from optic nerve damage can lead to the progressive death of retinal ganglion cells (RGCs), culminating in irreversible vision loss. We contrasted two methods for inducing optic nerve damage: optic nerve compression (ONCo) and optic nerve crush (ONCr). These were assessed for their respective merits in simulating traumatic optic neuropathies and neurodegeneration. We also administered neural progenitor cells (NPCs) into the subtenon space to validate their potential in mitigating optic nerve damage. Our findings indicate that both ONCo and ONCr successfully induced optic nerve damage, as shown by increased ischemia and expression of genes linked to neuronal regeneration. Post NPCs injection, recovery in the expression of neuronal regeneration-related genes was more pronounced in the ONCo model than in the ONCr model, while inflammation-related gene expression saw a better recovery in ONCr. In addition, proteomic analysis of R28 cells in hypoxic conditions identified Vps35 and Syntaxin12 genes. Vps35 preserved mitochondrial function in ONCo, while Syntaxin12 appeared to restrain inflammation via the Wnt/β-catenin signaling pathway in ONCr. NPCs managed to restore damaged RGCs by elevating neuroprotection factors and controlling inflammation through mitochondrial homeostasis and Wnt/β-catenin signaling in hypoxia-injured R28 cells and in both animal models. Our results suggest that ischemic injury and crush injury cause optic nerve damage via different mechanisms, which can be effectively simulated using ONCo and ONCr, respectively. Moreover, cell-based therapies such as NPCs may offer promising avenues for treating various optic neuropathies, including ischemic and crush injuries.

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Hypoxia-Preconditioned Placenta-Derived Mesenchymal Stem Cells Rescue Optic Nerve Axons Via Differential Roles of Vascular Endothelial Growth Factor in an Optic Nerve Compression Animal Model

Cited by 9 publications

References 42 publications

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 Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model

Mesenchymal stem cells for repairing glaucomatous optic nerve

Unveiling Neuroprotection and Regeneration Mechanisms in Optic Nerve Injury: Insight from Neural Progenitor Cell Therapy with Focus on Vps35 and Syntaxin12

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