Therapeutic efficacy of different routes of mesenchymal stem cell administration in corneal injury

Sachin Shukla; Sharad K Mittal; William Foulsham; Elsayed Elbasiony; Disha Singhania; Srikant K Sahu; Sunil K Chauhan

doi:10.1016/j.jtos.2019.07.005

Therapeutic efficacy of different routes of mesenchymal stem cell administration in corneal injury

Ocul Surf. 2019 Oct;17(4):729-736. doi: 10.1016/j.jtos.2019.07.005. Epub 2019 Jul 3.

Authors

Sachin Shukla¹, Sharad K Mittal², William Foulsham³, Elsayed Elbasiony², Disha Singhania², Srikant K Sahu⁴, Sunil K Chauhan⁵

Affiliations

¹ Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA; Center for Ocular Regeneration, L. V. Prasad Eye Institute, Hyderabad, India.
² Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
³ Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA; Institute of Ophthalmology, University College London, London, UK.
⁴ Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA; L.V. Prasad Eye Institute, Bhubaneswar, Odisha, India. Electronic address: srikantsahu@lvpei.org.
⁵ Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA. Electronic address: sunil_chauhan@meei.harvard.edu.

Abstract

Purpose: Corneal injuries are associated with significant impairment in vision. Mesenchymal stem cells (MSCs) have been shown to limit inflammation and promote tissue repair at the ocular surface. Here, we evaluate the efficacies of different modes of MSC delivery (topical, subconjunctival, intraperitoneal [IP] and intravenous [IV]) to promote tissue repair and restore corneal transparency in a murine model of corneal injury.

Methods: MSCs were purified from the bone marrow of C57BL/6 mice and expanded using plastic adherence in vitro. Corneal injury was created using an Algerbrush, and 0.5 × 10⁶ MSCs/mouse were administered via topical, subconjunctival, IP or IV routes. Qdot-labeled MSCs were employed to determine the effect of route of administration on corneal and conjunctival MSC frequencies. Corneal opacity scores were calculated using ImageJ. Expression of inflammatory cytokines was quantified by qPCR, and infiltration of CD45⁺ cells was evaluated by flow cytometry.

Results: Subconjunctival or IV administration results in increased frequencies of MSCs in ocular surface tissues following corneal injury, relative to topical or intraperitoneal delivery. Subconjunctival or IV administration reduces: (i) corneal opacity, (ii) tissue fibrosis as quantified by α-Sma expression, (iii) the expression of inflammatory cytokines (Il-1β and Tnf-α) and (iv) CD45⁺ inflammatory cell infiltration relative to untreated injured control animals. Administration via subconjunctival or IV routes was observed to accelerate corneal repair by restoring tissue architecture and epithelial integrity.

Conclusions: Our data suggest that subconjunctival or IV delivery of MSCs has superior therapeutic efficacy compared to topical or IP delivery following corneal injury.

Keywords: Corneal injury; Homing; Inflammation; Mesenchymal stem cells; Wound healing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cornea / pathology*
Corneal Injuries / diagnosis
Corneal Injuries / therapy*
Disease Models, Animal
Female
Injections
Male
Mesenchymal Stem Cell Transplantation / methods*
Mesenchymal Stem Cells / cytology*
Mice
Mice, Inbred C57BL
Treatment Outcome

Abstract

Publication types

MeSH terms

Grants and funding