Regeneration of Corneal Epithelium With Dental Pulp Stem Cells Using a Contact Lens Delivery System

Kushnerev, Evgeny; Shawcross, Susan; Sothirachagan, Shankari; Carley, Fiona; Brahma, Arun; Yates, Julian; Hillarby, M. C.

doi:10.1167/iovs.15-17953

Cited by 38 publications

(25 citation statements)

References 42 publications

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“…When cultured in a three-dimensional (3D) dentin scaffold, DP-MSCs can differentiate into corneal epithelial cells, melanocytes and induced pluripotent stem cells, rendering them highly useful in regenerative medicine research. 14,15,53 The most promising clinical applications for this stem cell source involve the correction of metabolic diseases and the treatment of liver diseases with high mortality rates, such as cirrhosis and hepatocellular carcinoma. 54,55 Over time, DP-MSCs have become the preferred alternative to harvesting stem cells during hepatic transplantation.…”

Section: At-mscs Regulate the Function Of T Cells By Promoting The Inmentioning

confidence: 99%

“…54,55 Over time, DP-MSCs have become the preferred alternative to harvesting stem cells during hepatic transplantation. 15 DP-MSCs have also been used in the field of bone regeneration. When DP-MSCs are cultured on hydrogels, they can spontaneously differentiate into both odontogenic and osteogenic phenotypes.…”

Section: At-mscs Regulate the Function Of T Cells By Promoting The Inmentioning

confidence: 99%

See 1 more Smart Citation

Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review

Berebichez-Fridman

Montero-Olvera

2018

Sultan Qaboos Univ Med J

328

211

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First discovered by Friedenstein in 1976, mesenchymal stem cells (MSCs) are adult stem cells found throughout the body that share a fixed set of characteristics. Discovered initially in the bone marrow, this cell source is considered the gold standard for clinical research, although various other sources—including adipose tissue, dental pulp, mobilised peripheral blood and birth-derived tissues—have since been identified. Although similar, MSCs derived from different sources possess distinct characteristics, advantages and disadvantages, including their differentiation potential and proliferation capacity, which influence their applicability. Hence, they may be used for specific clinical applications in the fields of regenerative medicine and tissue engineering. This review article summarises current knowledge regarding the various sources, characteristics and therapeutic applications of MSCs.Keywords: Mesenchymal Stem Cells; Adult Stem Cells; Regenerative Medicine; Cell Differentiation; Tissue Engineering.

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Section: At-mscs Regulate the Function Of T Cells By Promoting The Inmentioning

confidence: 99%

Section: At-mscs Regulate the Function Of T Cells By Promoting The Inmentioning

confidence: 99%

Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review

Berebichez-Fridman

Montero-Olvera

2018

Sultan Qaboos Univ Med J

328

211

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“…For this purpose, once the NS were obtained, these were cultured for 15 days in adhesion conditions to allow cell expansion. Total RNA was extracted when NS were formed (day 4) and at the end of the expansion process (day 19), in order to verify if the NCSC phenotype was maintained during the expansion process.…”

Section: Corneal Endothelial Cell Differentiationmentioning

confidence: 99%

“…Interestingly, DPSC, as well as CEC, arise from cranial NC and present similar characteristics to NC progenitor or stem cells [14,17]. Some recent studies proposed as well the use of DPSC as a possible cell source, nevertheless these works were mainly related with the corneal epithelium or the stroma [18,19]. Therefore, in this work we aim to determine if patient-derived DPSC, which share the same embryological origin with CEC, can be used as a potential autologous source for corneal endothelial regeneration, which to the best of our knowledge, has not been previously proposed.…”

Section: Introductionmentioning

confidence: 99%

A new alternative for corneal endothelial regeneration using autologous dental pulp stem cells

Bosch

Salero²,

Núñez-Toldrà

et al. 2020

Preprint

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Background Failure of the corneal endothelium cell (CEC) monolayer is the main cause leading to corneal transplantation. Autologous cell-based therapies are required to reconstruct in vitro the cell monolayer. For this purpose, we propose the use of dental pulp stem cells isolated from the third molars to form CEC monolayer. We hypothesize that by using dental pulp stem cells (DPSC) that share an embryological origin with CEC, as they both arise from the neural crest, may allow a direct differentiation process avoiding the use of reprogramming techniques, such as induced pluripotent stem cells (iPSC). Methods In this work, we report a two-step differentiation protocol, where dental pulp stem cells are derived into neural crest stem cells and, then, into CEC. Results Initially, we compared the efficiency of direct differentiation of DPSC with the differentiation of iPSC to express NCSC related genes in adhesion culture, showing significantly higher levels of early stage marker AP2 for the DPSC compared to iPSC. To provide better environment for NCSC gene expression, suspension method was performed, which induced the formation of neurospheres. The results showed neurosphere formation after few days, obtaining the peak of NCSC marker expression after 4 days, showing overexpression of AP2, p75 and CHD7 markers, confirming the formation of NCSC like cells. Furthermore, pluripotent markers Oct4, Nanog and Sox2 were as well upregulated in suspension culture. Neurospheres were then directly cultured in CEC conditioned medium for the second differentiation, showing the conversion of DPSC into polygonal like cells expressing higher levels of ZO-1, ATP1A1, COL4A2 and COL8A1 markers, providing proof of the successful conversion into CEC. Conclusions Therefore, our findings demonstrate that patient-derived dental pulp stem cells represent an autologous cell source for corneal endothelial regeneration that avoids actual transplantation limitations as well as reprogramming techniques.

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“…Investigators described that the cell/ scaffold construct once transplanted in-vivo , DPSCs had transferred from the contact lenses to the corneal surface and began to express the corneal specific markers cytokeratins 3 and 12. In addition to the expression of these markers, the DPSCs were able to prevent conjunctival cells from growing in the central cornea (Yam et al, 2015 ; Kushnerev et al, 2016 ).…”

Section: Dental Mesenchymal Stem Cells Beyond Regenerative Dentistrymentioning

confidence: 99%

Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement

Marei

Backly

2018

Front. Bioeng. Biotechnol.

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Dentistry is a continuously changing field that has witnessed much advancement in the past century. Prosthodontics is that branch of dentistry that deals with replacing missing teeth using either fixed or removable appliances in an attempt to simulate natural tooth function. Although such “replacement therapies” appear to be easy and economic they fall short of ever coming close to their natural counterparts. Complications that arise often lead to failures and frequent repairs of such devices which seldom allow true physiological function of dental and oral-maxillofacial tissues. Such factors can critically affect the quality of life of an individual. The market for dental implants is continuously growing with huge economic revenues. Unfortunately, such treatments are again associated with frequent problems such as peri-implantitis resulting in an eventual loss or replacement of implants. This is particularly influential for patients having co-morbid diseases such as diabetes or osteoporosis and in association with smoking and other conditions that undoubtedly affect the final treatment outcome. The advent of tissue engineering and regenerative medicine therapies along with the enormous strides taken in their associated interdisciplinary fields such as stem cell therapy, biomaterial development, and others may open arenas to enhancing tissue regeneration via designing and construction of patient-specific biological and/or biomimetic substitutes. This review will overview current strategies in regenerative dentistry while overviewing key roles of dental mesenchymal stem cells particularly those of the dental pulp, until paving the way to precision/translational regenerative medicine therapies for future clinical use.

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Regeneration of Corneal Epithelium With Dental Pulp Stem Cells Using a Contact Lens Delivery System

Abstract: Citation: Kushnerev E, Shawcross SG, Sothirachagan S, et al. Regeneration of corneal epithelium with dental pulp stem cells using a contact lens delivery system.

Cited by 38 publications

References 42 publications

Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review

Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review

A new alternative for corneal endothelial regeneration using autologous dental pulp stem cells

Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement

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