June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Bone marrow- and adipose tissue-derived mesenchymal stem cells partially restore corneal and limbal epithelial phenotype in a rabbit model of limbal stem cell deficiency
Author Affiliations & Notes
  • Ana De-La-Mata
    IOBA -Institute of Applied Ophthalmobiology, Universidad de Valladolid, Valladolid, Castilla y León, Spain
    CIBER-BBN (Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine), Instituto de Salud Carlos III, Valladolid, Spain
  • Sara Galindo
    IOBA -Institute of Applied Ophthalmobiology, Universidad de Valladolid, Valladolid, Castilla y León, Spain
    CIBER-BBN (Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine), Instituto de Salud Carlos III, Valladolid, Spain
  • Marina Lopez-Paniagua
    IOBA -Institute of Applied Ophthalmobiology, Universidad de Valladolid, Valladolid, Castilla y León, Spain
    CIBER-BBN (Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine), Instituto de Salud Carlos III, Valladolid, Spain
  • Jose Maria Herreras Cantalapiedra
    IOBA -Institute of Applied Ophthalmobiology, Universidad de Valladolid, Valladolid, Castilla y León, Spain
    Department of Ophthalmology, Clinic University Hospital, Valladolid, Spain
  • Carmen García-Vazquez
    IOBA -Institute of Applied Ophthalmobiology, Universidad de Valladolid, Valladolid, Castilla y León, Spain
    Regional Center for Regenerative Medicine and Cell Therapy, Spain
  • Beatriz Marceñido
    IOBA -Institute of Applied Ophthalmobiology, Universidad de Valladolid, Valladolid, Castilla y León, Spain
  • Margarita Calonge
    IOBA -Institute of Applied Ophthalmobiology, Universidad de Valladolid, Valladolid, Castilla y León, Spain
    CIBER-BBN (Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine), Instituto de Salud Carlos III, Valladolid, Spain
  • Teresa Nieto-Miguel
    IOBA -Institute of Applied Ophthalmobiology, Universidad de Valladolid, Valladolid, Castilla y León, Spain
    CIBER-BBN (Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine), Instituto de Salud Carlos III, Valladolid, Spain
  • Footnotes
    Commercial Relationships   Ana De-La-Mata None; Sara Galindo None; Marina Lopez-Paniagua None; Jose Maria Herreras Cantalapiedra None; Carmen García-Vazquez None; Beatriz Marceñido None; Margarita Calonge None; Teresa Nieto-Miguel None
  • Footnotes
    Support  Ministries of Economy and Competitiveness (SAF2015-63594-R MINECO/FEDER, EU) and of Science and Innovation (PID2019-105525RB-100 and CIBER-BBN CB06/01/003; MICINN/FEDER, EU), Spain. Regional Center for Regenerative Medicine and Cell Therapy, Castilla y León, Spain.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 92 – A0190. doi:
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    • Get Citation

      Ana De-La-Mata, Sara Galindo, Marina Lopez-Paniagua, Jose Maria Herreras Cantalapiedra, Carmen García-Vazquez, Beatriz Marceñido, Margarita Calonge, Teresa Nieto-Miguel; Bone marrow- and adipose tissue-derived mesenchymal stem cells partially restore corneal and limbal epithelial phenotype in a rabbit model of limbal stem cell deficiency. Invest. Ophthalmol. Vis. Sci. 2022;63(7):92 – A0190.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Limbal stem cell deficiency (LSCD) occurs as a result of limbal stem cell damage and/or sclerocorneal limbal niche destruction. Our research group has recently demonstrated that transplantation of both bone marrow- and adipose tissue-derived mesenchymal stem cells (BM-MSCs and AT-MSCs) in a LSCD rabbit model reduces the development of corneal opacity, and partially restores the tissue structure of the damaged ocular surface. The aim of this work was to study the effect of BM-MSC and AT-MSC transplantation on the corneal and limbal epithelial phenotype of a rabbit model of ocular surface failure due to LSCD.

Methods : A total LSCD model was developed in 15 New Zealand white rabbits through 360 surgical limbal peritomy after N-heptanol-based denudation of the corneal surface. Three weeks after the injury, 10 rabbits were transplanted with 250,000 human MSCs on amniotic membrane (5 with BM-MSCs; 5 with AT-MSCs) and 5 non-transplanted animals formed the untreated group. At the end of the follow-up (11 weeks), immunofluorescence studies in ocular surface tissue sections were done to analyze the expression of corneal (CK3, E-cadherin) and limbal (CK15, p63) epithelial cell specific markers. Fluorescence intensity was measured using ImageJ software in 2 tissue sections per rabbit.

Results : E-cadherin expression was similar in untreated LSCD eyes and healthy control eyes, but it significantly increased in LSCD eyes after BM-MSC transplantation. The expression of CK3, CK15 and p63 was significantly reduced in untreated LSCD eyes compared to healthy control eyes, but transplantation of both BM-MSCs and AT-MSCs in LSCD eyes induced a partial (CK15) or an almost full (CK3 and p63) recovery of their expression levels. Nevertheless, the expression levels achieved were in general higher in the eyes treated with BM-MSCs than in those treated with AT-MSCs.

Conclusions : Although the effect of BM-MSC transplantation seems slightly superior, transplantation of both BM-MSCs and AT-MSCs in a LSCD rabbit model partially restores corneal and limbal epithelial phenotype. Therefore, both types of MSCs seem valid alternatives for the treatment of LSCD.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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