In Vivo Confocal Microscopy in Limbal Stem Cell Deficiency After Mesenchymal Stem Cell Transplantation: A Sub-analysis from a Phase I–II Clinical Trial

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Introduction

The aim of this work is to evaluate the effect of mesenchymal stem cell transplantation (MSCT) and cultivated limbal epithelial transplantation (CLET) therapies on the limbus of patients suffering from limbal stem cell deficiency (LSCD).

Methods

A sub-analysis of a phase I–II randomized, controlled, and double-masked clinical trial was performed to assess the changes in the anatomical structures of the limbus. In vivo confocal microscopy (IVCM) analysis was carried out in LSCD eyes before and 12 months after allogeneic MSCT or CLET. Epithelial phenotype of the central cornea, as well as the presence of transition zones and palisades of Vogt in the limbus, were assessed using Wilcoxon test.

Results

Twenty-three LSCD (14 MSCT and nine CLET) eyes were included. The epithelial phenotype of the central cornea improved significantly ( p < 0.001) from 15 (eight MSCT, seven CLET) and eight (six MSCT, two CLET) LSCD eyes showing conjunctival and mixed phenotypes, respectively, to eight (five MSCT, three CLET), five (two MSCT, three CLET), and ten (seven MSCT, three CLET) eyes showing conjunctival, mixed, and corneal phenotypes, respectively. Transition areas and palisades of Vogt were observed in at least one quadrant in nine (five MSCT, four CLET) and 16 (nine MSCT, seven CLET), and in four (two MSCT, two CLET) and six (three MSCT, three CLET) LSCD eyes before and after surgery, respectively. Changes in the transition zones and palisades were solely significant ( p = 0.046) for the nasal and inferior quadrants, respectively.

Conclusions

MSCT and CLET improved the central corneal epithelial phenotype despite only minor changes in the anatomical structures of the limbus, as detected by IVCM technology.

Trial Registration

ClinicalTrials.gov identifier, NCT01562002.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40123-023-00809-7.

Related collections

Most cited references 42

Record: found
Abstract: found
Article: not found

Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells.

George Cotsarelis, Shih-Zen Cheng, Gang Dong … (1989)

Despite the obvious importance of epithelial stem cells in tissue homeostasis and tumorigenesis, little is known about their specific location or biological characteristics. Using 3H-thymidine labeling, we have identified a subpopulation of corneal epithelial basal cells, located in the peripheral cornea in a region called limbus, that are normally slow cycling, but can be stimulated to proliferate in response to wounding and to a tumor promotor, TPA. No such cells can be detected in the central corneal epithelium, suggesting that corneal epithelial stem cells are located in the limbus. A comparison of various types of epithelial stem cells revealed a common set of features, including their preferred location, pigment protection, and growth properties, which presumably play a crucial role in epithelial stem cell function.

0 comments Cited 252 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing.

Giselle Chamberlain, James Forrest Fox, Brian Ashton … (2007)

MSCs are nonhematopoietic stromal cells that are capable of differentiating into, and contribute to the regeneration of, mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, and adipose. MSCs are rare in bone marrow, representing approximately 1 in 10,000 nucleated cells. Although not immortal, they have the ability to expand manyfold in culture while retaining their growth and multilineage potential. MSCs are identified by the expression of many molecules including CD105 (SH2) and CD73 (SH3/4) and are negative for the hematopoietic markers CD34, CD45, and CD14. The properties of MSCs make these cells potentially ideal candidates for tissue engineering. It has been shown that MSCs, when transplanted systemically, are able to migrate to sites of injury in animals, suggesting that MSCs possess migratory capacity. However, the mechanisms underlying the migration of these cells remain unclear. Chemokine receptors and their ligands and adhesion molecules play an important role in tissue-specific homing of leukocytes and have also been implicated in trafficking of hematopoietic precursors into and through tissue. Several studies have reported the functional expression of various chemokine receptors and adhesion molecules on human MSCs. Harnessing the migratory potential of MSCs by modulating their chemokine-chemokine receptor interactions may be a powerful way to increase their ability to correct inherited disorders of mesenchymal tissues or facilitate tissue repair in vivo. The current review describes what is known about MSCs and their capacity to home to tissues together with the associated molecular mechanisms involving chemokine receptors and adhesion molecules.

0 comments Cited 197 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Immunomodulatory properties of mesenchymal stromal cells.

Alma Nauta, Willem E Fibbe (2007)

Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitor cells capable of differentiating into multiple lineages of the mesenchyme. MSCs have emerged as a promising therapeutic modality for tissue regeneration and repair. Further clinical interest has been raised by the observation that MSCs are immunoprivileged and, more importantly, display immunomodulatory capacities. Although the mechanisms underlying the immunosuppressive effects of MSCs have not been clearly defined, their immunosuppressive properties have already been exploited in the clinical setting. The aim of this review is to critically discuss the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms, the potential clinical use of MSCs as modulators of immune responses in vivo, and to indicate clinical safety concerns and recommendations for future research.

0 comments Cited 150 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Alberto López-Miguel:

ORCID: http://orcid.org/0000-0001-9429-1571

alopezm@ioba.med.uva.es

Journal

Journal ID (nlm-ta): Ophthalmol Ther

Journal ID (iso-abbrev): Ophthalmol Ther

Title: Ophthalmology and Therapy

Publisher: Springer Healthcare (Cheshire )

ISSN (Print): 2193-8245

ISSN (Electronic): 2193-6528

Publication date (Electronic): 29 September 2023

Publication date PMC-release: 29 September 2023

Publication date (Print): December 2023

Volume: 12

Issue: 6

Pages: 3251-3262

Affiliations

[1 ]IOBA (Institute of Applied Ophthalmobiology), Universidad de Valladolid, ( https://ror.org/01fvbaw18) Campus Miguel Delibes, Paseo Belén, 17, 47011 Valladolid, Spain

[2 ]CIBER-BBN (Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine), Carlos III National Institute of Health, ( https://ror.org/01gm5f004) Valladolid, Spain

[3 ]Department of Cell Biology, Genetics, Histology and Pharmacology, Universidad de Valladolid, ( https://ror.org/01fvbaw18) Valladolid, Spain

[4 ]Departamento de Cirugía, Oftalmología, Otorrinolaringología y Fisioterapia, Facultad de Medicina, Universidad de Valladolid, ( https://ror.org/01fvbaw18) Valladolid, Spain

[5 ]Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Valladolid, Spain

[6 ]GRID grid.5239.d, ISNI 0000 0001 2286 5329, IBGM (Institute of Molecular Biology and Genetics) and University Scientific Park, , Universidad de Valladolid, ; Valladolid, Spain

Author information

Alberto López-Miguel http://orcid.org/0000-0001-9429-1571

Article

Publisher ID: 809

DOI: 10.1007/s40123-023-00809-7

PMC ID: 10640524

PubMed ID: 37773479

SO-VID: 28f37faa-4670-4bfe-b42e-00911aed1590

License:

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 30 May 2023

Date accepted : 31 August 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004837, Ministerio de Ciencia e Innovación;

Award ID: PID2021-125142OA-I00

Award ID: PID2019-105525RB-100

Award Recipient : Alberto López-Miguel Teresa Nieto-Miguel

Funded by: FundRef http://dx.doi.org/10.13039/100016145, Ministerio de Sanidad, Consumo y Bienestar Social;

Award ID: SAS/2377/2010 EC10-256

Award Recipient : Margarita Calonge

Funded by: FundRef http://dx.doi.org/10.13039/501100005053, Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina;

Award ID: CB06/01/003

Award Recipient : Margarita Calonge

Custom metadata

Keywords: limbal stem cell deficiency,mesenchymal stem cell transplantation (msct),cultivated limbal epithelial transplantation (clet),in vivo confocal microscopy,corneal blindness

Data availability:

Keywords: limbal stem cell deficiency, mesenchymal stem cell transplantation (msct), cultivated limbal epithelial transplantation (clet), in vivo confocal microscopy, corneal blindness

In Vivo Confocal Microscopy in Limbal Stem Cell Deficiency After Mesenchymal Stem Cell Transplantation: A Sub-analysis from a Phase I–II Clinical Trial

Read this article at

Abstract

Introduction

Methods

Results

Conclusions

Trial Registration

Supplementary Information

Related collections

Stress signalling in stem cells

Most cited references 42

Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells.

Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing.

Immunomodulatory properties of mesenchymal stromal cells.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 334

Most referenced authors 342