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Therapeutic Potential of Oral-Derived Mesenchymal Stem Cells in Retinal Repair

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Abstract

The retina has restricted regeneration ability to recover injured cell layer because of reduced production of neurotrophic factors and increased inhibitory molecules against axon regrowth. A diseased retina could be regenerated by repopulating the damaged tissue with functional cell sources like mesenchymal stem cells (MSCs). The cells are able to release neurotrophic factors (NFs) to boost axonal regeneration and cell maintenance. In the current study, we comprehensively explore the potential of various types of stem cells (SCs) from oral cavity as promising therapeutic options in retinal regeneration. The oral MSCs derived from cranial neural crest cells (CNCCs) which explains their broad neural differentiation potential and secret rich NFs. They are comprised of dental pulp SCs (DPSCs), SCs from exfoliated deciduous teeth (SHED), SCs from apical papilla (SCAP), periodontal ligament-derived SCs (PDLSCs), gingival MSCs (GMSCs), and dental follicle SCs (DFSCs). The Oral MSCs are becoming a promising source of cells for cell-free or cell-based therapeutic approach to recover degenerated retinal. These cells have various mechanisms of action in retinal regeneration including cell replacement and the paracrine effect. It was demonstrated that they have more neuroprotective and neurotrophic effects on retinal cells than immediate replacement of injured cells in retina. This could be the reason that their therapeutic effects would be weakened over time. It can be concluded that neuronal and retinal regeneration through these cells is most likely due to their NFs that dramatically suppress oxidative stress, inflammation, and apoptosis. Although, oral MSCs are attractive therapeutic options for retinal injuries, more preclinical and clinical investigations are required.

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Abbreviations

MSCs:

Mesenchymal stem cells

DPSCs:

Dental pulp stem cells

SHED:

Stem cells from exfoliated deciduous teeth

SCAP:

Stem cells from apical papilla

PDLSCs:

Periodontal ligament stem cells

GMSCs:

Gingival MSCs

GMPCs:

Gingival multipotent progenitor cells

DFSC:

Dental follicle stem cells

CNCCs:

Cranial neural crest derived ectomesenchymal cells

PDL:

Periodontal ligament

BM-MSCs:

Bone marrow mesenchymal stem cells

CM:

Conditioned medium

RGCs:

Retinal ganglion cells

RPE:

Retinal pigment epithelium

NSCs:

Neural stem cells

ASCs:

Adult stem cells

iPSCs:

induced pluripotent stem cells

ESCs:

Embryonic stem cells

bFGF:

Basic fibroblast growth factor

IGF-1:

Insulin-like growth factor-1

NGF:

Nerve growth factor

EGF:

Epidermal growth factor

BDNF:

Brain-derived neurotrophic factor

IL-1β:

interleukin-1β

TNF-α:

Tumor necrosis factor-α

SHH:

Sonic hedgehog

VGF:

VGF nerve growth factor inducible

NFM:

neurofilament protein

ONL:

Outer nuclear layer

INL:

Inner nuclear layer

BMP:

Bone morphogenic protein

NPCs:

Neural progenitor-like cells

DRG:

Dorsal root ganglion

NLCCs:

Neurosphere-like cell clusters

GD3:

Ganglioside D3

mDFPCs:

Murine dental follicle cells

VEGFA:

Vascular Endothelial Growth Factor A

CNTF:

Ciliary neurotrophic factor

NT-3:

Neurotrophin-3

GDNF:

Glial cell line-derived neurotrophic factor

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Acknowledgements

We appreciate all of the researchers in this field of study that we used their research to better understand the concept of this paper.

Funding

No grants, funds, or other financial support were received.

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Authors and Affiliations

  1. Department of Food Science & Technology, University of California, Davis, CA, 95616, USA

    Fariba Mohebichamkhorami

  2. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fariba Mohebichamkhorami & Hakimeh Zali

  3. Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran

    Zahra Niknam

  4. Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Ebrahim Mostafavi

  5. Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Ebrahim Mostafavi

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  1. Fariba Mohebichamkhorami
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  3. Hakimeh Zali
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Mohebichamkhorami, F., Niknam, Z., Zali, H. et al. Therapeutic Potential of Oral-Derived Mesenchymal Stem Cells in Retinal Repair. Stem Cell Rev and Rep 19, 2709–2723 (2023). https://doi.org/10.1007/s12015-023-10626-x

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