@article {1608580,
	title = {Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {10},
	year = {2021},
	month = {2021 Aug 12},
	pages = {3},
	abstract = {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\% {\textpm} 2.1\% and 94.9\% {\textpm} 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\% {\textpm} 12.1\% in epithelial cells co-cultured with MSCs compared with 40.8\% {\textpm} 23.1\% in controls. At 24 hours after wounding, all MSC-injected murine eyes had 100\% corneal wound closure compared with 79.9\% {\textpm} 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.},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.10.3},
	author = {Putra, Ilham and Shen, Xiang and Anwar, Khandaker N and Rabiee, Behnam and Samaeekia, Ravand and Almazyad, Enmar and Giri, Pushpanjali and Jabbehdari, Sayena and Hayat, Mohammed R and Elhusseiny, Abdelrahman M and Ghassemi, Mahmood and Mahmud, Nadim and Edward, Deepak P and Joslin, Charlotte E and Rosenblatt, Mark I and Dana, Reza and Eslani, Medi and Hematti, Peiman and Djalilian, Ali R}
}
