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Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair
PURPOSE: Mesenchymal stromal cells (MSCs) have been shown to enhance tissue repair as a cell-based therapy. In preparation for a phase I clinical study, we evaluated the safety, dosing, and efficacy of bone marrow–derived MSCs after subconjunctival injection in preclinical animal models of mice, rat...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362636/ https://www.ncbi.nlm.nih.gov/pubmed/34383879 http://dx.doi.org/10.1167/tvst.10.10.3 |
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author | Putra, Ilham Shen, Xiang Anwar, Khandaker N. Rabiee, Behnam Samaeekia, Ravand Almazyad, Enmar Giri, Pushpanjali Jabbehdari, Sayena Hayat, Mohammed R. Elhusseiny, Abdelrahman M. Ghassemi, Mahmood Mahmud, Nadim Edward, Deepak P. Joslin, Charlotte E. Rosenblatt, Mark I. Dana, Reza Eslani, Medi Hematti, Peiman Djalilian, Ali R. |
author_facet | Putra, Ilham Shen, Xiang Anwar, Khandaker N. Rabiee, Behnam Samaeekia, Ravand Almazyad, Enmar Giri, Pushpanjali Jabbehdari, Sayena Hayat, Mohammed R. Elhusseiny, Abdelrahman M. Ghassemi, Mahmood Mahmud, Nadim Edward, Deepak P. Joslin, Charlotte E. Rosenblatt, Mark I. Dana, Reza Eslani, Medi Hematti, Peiman Djalilian, Ali R. |
author_sort | Putra, Ilham |
collection | PubMed |
description | PURPOSE: Mesenchymal stromal cells (MSCs) have been shown to enhance tissue repair as a cell-based therapy. In preparation for a phase I clinical study, we evaluated the safety, dosing, and efficacy of bone marrow–derived MSCs after subconjunctival injection in preclinical animal models of mice, rats, and rabbits. METHODS: Human bone marrow–derived MSCs were expanded to passage 4 and cryopreserved. Viability of MSCs after thawing and injection through small-gauge needles was evaluated by vital dye staining. The in vivo safety of human and rabbit MSCs was studied by subconjunctivally injecting MSCs in rabbits with follow-up to 90 days. The potency of MSCs on accelerating wound healing was evaluated in vitro using a scratch assay and in vivo using 2-mm corneal epithelial debridement wounds in mice. Human MSCs were tracked after subconjunctival injection in rat and rabbit eyes. RESULTS: The viability of MSCs after thawing and immediate injection through 27- and 30-gauge needles was 93.1% ± 2.1% and 94.9% ± 1.3%, respectively. Rabbit eyes demonstrated mild self-limiting conjunctival inflammation at the site of injection with human but not rabbit MSCs. In scratch assay, the mean wound healing area was 93.5% ± 12.1% in epithelial cells co-cultured with MSCs compared with 40.8% ± 23.1% in controls. At 24 hours after wounding, all MSC-injected murine eyes had 100% corneal wound closure compared with 79.9% ± 5.5% in controls. Human MSCs were detectable in the subconjunctival area and peripheral cornea at 14 days after injection. CONCLUSIONS: Subconjunctival administration of MSCs is safe and effective in promoting corneal epithelial wound healing in animal models. TRANSLATIONAL RELEVANCE: These results provide preclinical data to support a phase I clinical study. |
format | Online Article Text |
id | pubmed-8362636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-83626362021-08-24 Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair Putra, Ilham Shen, Xiang Anwar, Khandaker N. Rabiee, Behnam Samaeekia, Ravand Almazyad, Enmar Giri, Pushpanjali Jabbehdari, Sayena Hayat, Mohammed R. Elhusseiny, Abdelrahman M. Ghassemi, Mahmood Mahmud, Nadim Edward, Deepak P. Joslin, Charlotte E. Rosenblatt, Mark I. Dana, Reza Eslani, Medi Hematti, Peiman Djalilian, Ali R. Transl Vis Sci Technol Special Issue PURPOSE: Mesenchymal stromal cells (MSCs) have been shown to enhance tissue repair as a cell-based therapy. In preparation for a phase I clinical study, we evaluated the safety, dosing, and efficacy of bone marrow–derived MSCs after subconjunctival injection in preclinical animal models of mice, rats, and rabbits. METHODS: Human bone marrow–derived MSCs were expanded to passage 4 and cryopreserved. Viability of MSCs after thawing and injection through small-gauge needles was evaluated by vital dye staining. The in vivo safety of human and rabbit MSCs was studied by subconjunctivally injecting MSCs in rabbits with follow-up to 90 days. The potency of MSCs on accelerating wound healing was evaluated in vitro using a scratch assay and in vivo using 2-mm corneal epithelial debridement wounds in mice. Human MSCs were tracked after subconjunctival injection in rat and rabbit eyes. RESULTS: The viability of MSCs after thawing and immediate injection through 27- and 30-gauge needles was 93.1% ± 2.1% and 94.9% ± 1.3%, respectively. Rabbit eyes demonstrated mild self-limiting conjunctival inflammation at the site of injection with human but not rabbit MSCs. In scratch assay, the mean wound healing area was 93.5% ± 12.1% in epithelial cells co-cultured with MSCs compared with 40.8% ± 23.1% in controls. At 24 hours after wounding, all MSC-injected murine eyes had 100% corneal wound closure compared with 79.9% ± 5.5% in controls. Human MSCs were detectable in the subconjunctival area and peripheral cornea at 14 days after injection. CONCLUSIONS: Subconjunctival administration of MSCs is safe and effective in promoting corneal epithelial wound healing in animal models. TRANSLATIONAL RELEVANCE: These results provide preclinical data to support a phase I clinical study. The Association for Research in Vision and Ophthalmology 2021-08-12 /pmc/articles/PMC8362636/ /pubmed/34383879 http://dx.doi.org/10.1167/tvst.10.10.3 Text en Copyright 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
spellingShingle | Special Issue Putra, Ilham Shen, Xiang Anwar, Khandaker N. Rabiee, Behnam Samaeekia, Ravand Almazyad, Enmar Giri, Pushpanjali Jabbehdari, Sayena Hayat, Mohammed R. Elhusseiny, Abdelrahman M. Ghassemi, Mahmood Mahmud, Nadim Edward, Deepak P. Joslin, Charlotte E. Rosenblatt, Mark I. Dana, Reza Eslani, Medi Hematti, Peiman Djalilian, Ali R. Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair |
title | Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair |
title_full | Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair |
title_fullStr | Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair |
title_full_unstemmed | Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair |
title_short | Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair |
title_sort | preclinical evaluation of the safety and efficacy of cryopreserved bone marrow mesenchymal stromal cells for corneal repair |
topic | Special Issue |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362636/ https://www.ncbi.nlm.nih.gov/pubmed/34383879 http://dx.doi.org/10.1167/tvst.10.10.3 |
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