Cultured Autologous Corneal Epithelia for the Treatment of Unilateral Limbal Stem Cell Deficiency: A Case Series of 15 Patients

Guérin, Louis-Philippe; Larouche, Danielle; Morcos, Mohib; Faucher, Anne; Auger, François A.; Knoppers, Bartha Maria; Kyrillos, Ralph; Bazin, Richard; Germain, Lucie

doi:10.3390/biomedicines10081958

Cited by 4 publications

(1 citation statement)

References 37 publications

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“…Examples of cultured cells with TAC characteristics adopted to repair damaged epithelia are cultured keratinocytes from epidermis ( Gallico et al, 1984 ; de Luca et al, 1989 ), urethra ( Romagnoli et al, 1990 ; Raya-Rivera et al, 2011 ), corneal epithelium ( Pellegrini et al, 1997 ; Guérin et al, 2022 ). We already discussed at length in a previous section of this review why cultured Mesenchymal Stem Cells (MSCs), derived in most cases from bone-marrow or adipose, could be regarded as TACs.…”

Section: In Vitro Cultured Cells: Are They Equivalent To Tra...mentioning

confidence: 99%

Transit Amplifying Cells (TACs): a still not fully understood cell population

Cancedda

Mastrogiacomo

2023

Front. Bioeng. Biotechnol.

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Maintenance of tissue homeostasis and tissue regeneration after an insult are essential functions of adult stem cells (SCs). In adult tissues, SCs proliferate at a very slow rate within “stem cell niches”, but, during tissue development and regeneration, before giving rise to differentiated cells, they give rise to multipotent and highly proliferative cells, known as transit-amplifying cells (TACs). Although differences exist in diverse tissues, TACs are not only a transitory phase from SCs to post-mitotic cells, but they also actively control proliferation and number of their ancestor SCs and proliferation and differentiation of their progeny toward tissue specific functional cells. Autocrine signals and negative and positive feedback and feedforward paracrine signals play a major role in these controls. In the present review we will consider the generation and the role played by TACs during development and regeneration of lining epithelia characterized by a high turnover including epidermis and hair follicles, ocular epithelial surfaces, and intestinal mucosa. A comparison between these different tissues will be made. There are some genes and molecular pathways whose expression and activation are common to most TACs regardless their tissue of origin. These include, among others, Wnt, Notch, Hedgehog and BMP pathways. However, the response to these molecular signals can vary in TACs of different tissues. Secondly, we will consider cultured cells derived from tissues of mesodermal origin and widely adopted for cell therapy treatments. These include mesenchymal stem cells and dedifferentiated chondrocytes. The possible correlation between cell dedifferentiation and reversion to a transit amplifying cell stage will be discussed.

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Section: In Vitro Cultured Cells: Are They Equivalent To Tra...mentioning

confidence: 99%

Transit Amplifying Cells (TACs): a still not fully understood cell population

Cancedda

Mastrogiacomo

2023

Front. Bioeng. Biotechnol.

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Cultivation of limbal stem cells on a biopolymer carrier (preliminary study)

Andreev

Rogovaya

et al. 2023

Genes & Cells

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Limbal stem cell deficiency (LSCD) is a complicated pathology of ocular surface, which is not always helped by conservative methods of treatment and surgery is limited by available sources of tissue. Consequently, searching for new effective methods of its treatment is now gaining popularity. The most promising approach is transplantation of tissue-engineered constructs (TECs) consisting of cultured limbal stem cells and variety of biopolymer carriers. Purpose: This study was performed to obtain and characterize a TEC consisting of cultured limbal stem cells (LSCs) and collagen membrane. Methods: The study was performed at the Krasnov Research Institute at the Krasnov Research Institute of Eye Diseases and Koltzov Institute of Developmental Biology in cooperation with Imtek Ltd. with a series of experiments. 2 Chinchilla rabbits with an average weight of 3.5 kg and age of 6 months have been involved in this trial. LSCs were isolated and cultured in vitro from the healthy eye of rabbits using a method modified by the authors. Cells were cultured within 14 days and then transplanted to the collagen membrane. Immunofluorescent analysis of cells in the obtained TEC and vital dye staining were performed. Results: As a result, the cells isolated from the biopsy were a mixture of fibroblast-type cells and cells with characteristics of LSC. They maintained high survivability, proliferativity, phenotype and stemness on the collagen carrier according to immunofluorescent study. Conclusion: Thus, the abstained TEC could be used for further transplantation to the affected eye with LSCD.

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Matrix-Assisted Cell Transplantation for the Treatment of Limbal Stem Cell Deficiency in a Rabbit Model

Yu,

Andreev,

Rogovaya

et al. 2024

Biomedicines

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With the development of regenerative medicine in ophthalmology, the identification of cells with high proliferative potential in the limbal area has attracted the attention of ophthalmologists and offered a new option for treatment in clinical practice. Limbal stem cell deficiency (LSCD) is an identified eye disease with a difficult and negative outcome, for which the traditional treatment is keratoplasty. This study sought to evaluate the efficacy of matrix-assisted cell transplantation consisting of in vitro-cultured autologous limbal stem cells (LSCs) and type I collagen for the treatment of LSCD in rabbits. LSCD was induced in 10 rabbits by a combination of mechanical limbectomy and alkali burns. Cells were cultured on a plate for 14 days before being transferred to a collagen-based matrix for another 7 days. Rabbits were divided into two groups as follows: the experimental group (five rabbits) received matrix-assisted cell transplantation, while the control group (five rabbits) received only conservative therapy with anti-inflammatory eye drops. During the postoperative period, all rabbits were examined using slit-lamp biomicroscopy with photo-registration and fluorescent staining, impression cytology and anterior segment optical coherence tomography (AS-OCT). Rabbits were euthanized at 30 and 120 days, and their corneas were processed for histology and immunohistochemistry. As a consequence, rabbits in the experimental group demonstrated the restoration of the corneal epithelium and transparency without epithelial defects. Moreover, goblet cells were absent in the central zone of the corneal epithelium. In conclusion, our new method of treatment enhanced the corneal surface and is an effective method of treatment for LSCD in rabbits.

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Cultured Autologous Corneal Epithelia for the Treatment of Unilateral Limbal Stem Cell Deficiency: A Case Series of 15 Patients

Cited by 4 publications

References 37 publications

Transit Amplifying Cells (TACs): a still not fully understood cell population

Transit Amplifying Cells (TACs): a still not fully understood cell population

Cultivation of limbal stem cells on a biopolymer carrier (preliminary study)

Matrix-Assisted Cell Transplantation for the Treatment of Limbal Stem Cell Deficiency in a Rabbit Model

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