Mohammad Soleimani , Reza Mirshahi , Kasra Cheraqpour , Seyed Mahbod Baharnoori , Hamed Massoumi , Collin Chow , Sumaiya Shahjahan , Bita Momenaei , Mohammad Javad Ashraf , Raghuram Koganti , Mahmood Ghassemi , Khandaker N. Anwar , Elmira Jalilian , Ali R. Djalilian
{"title":"基质内与结膜下注射间充质干细胞/基质细胞促进角膜修复。","authors":"Mohammad Soleimani , Reza Mirshahi , Kasra Cheraqpour , Seyed Mahbod Baharnoori , Hamed Massoumi , Collin Chow , Sumaiya Shahjahan , Bita Momenaei , Mohammad Javad Ashraf , Raghuram Koganti , Mahmood Ghassemi , Khandaker N. Anwar , Elmira Jalilian , Ali R. Djalilian","doi":"10.1016/j.jtos.2023.09.008","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>Different approaches to delivery of mesenchymal stem/stromal cells (MSCs) for ameliorating corneal injuries<span> have been investigated. This study was aimed to compare the efficacy of intrastromal and subconjunctival injection of human bone marrow-derived MSCs (hBM-MSCs) in a corneal epithelial injury model.</span></p></div><div><h3>Methods</h3><p><span>Twenty-four C57BL/6J mice underwent total corneal and limbal epithelial debridement<span>. Then, the mice were divided into three different groups: (1) intrastromal hBM-MSCs injection, (2) subconjunctival hBM-MSCs injection, and (3) injection of frozen medium as a control. Mice were monitored by slit lamp<span> and underwent anterior segment optical coherence tomography (ASOCT). Following euthanasia, the corneas were further evaluated by histology and </span></span></span>immunostaining.</p></div><div><h3>Results</h3><p><span>hBM-MSC injection successfully healed epithelial defects<span><span><span> regardless of the delivery route (P < 0.001). However, intrastromal injection was superior to subconjunctival injection in reducing defect area (P = 0.001). Intrastromal injection of hBM-MSCs also significantly reduced </span>corneal opacity and </span>neovascularization<span> and improved ASOCT parameters compared to subconjunctival injection or no treatment<span> (P < 0.001, P = 0.003, and P < 0.001, respectively). Although both of the treatment groups were positive for CK12 and had reduced levels of MUC5AC compared to the control, CK12 staining was stronger in the intrastromal group compared to the subconjunctival group. Also, persistency of MSCs was confirmed by </span></span></span></span><em>in vivo</em> (up to 2 weeks) and <em>in vitro</em> assessments (up to 4 weeks).</p></div><div><h3>Conclusions</h3><p>Although the injection of hBM-MSC using both intrastromal and subconjunctival methods improve wound healing and reduce neovascularization and opacity, the intrastromal approach is superior in terms of corneal healing.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Intrastromal versus subconjunctival injection of mesenchymal stem/stromal cells for promoting corneal repair\",\"authors\":\"Mohammad Soleimani , Reza Mirshahi , Kasra Cheraqpour , Seyed Mahbod Baharnoori , Hamed Massoumi , Collin Chow , Sumaiya Shahjahan , Bita Momenaei , Mohammad Javad Ashraf , Raghuram Koganti , Mahmood Ghassemi , Khandaker N. Anwar , Elmira Jalilian , Ali R. Djalilian\",\"doi\":\"10.1016/j.jtos.2023.09.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><p>Different approaches to delivery of mesenchymal stem/stromal cells (MSCs) for ameliorating corneal injuries<span> have been investigated. This study was aimed to compare the efficacy of intrastromal and subconjunctival injection of human bone marrow-derived MSCs (hBM-MSCs) in a corneal epithelial injury model.</span></p></div><div><h3>Methods</h3><p><span>Twenty-four C57BL/6J mice underwent total corneal and limbal epithelial debridement<span>. Then, the mice were divided into three different groups: (1) intrastromal hBM-MSCs injection, (2) subconjunctival hBM-MSCs injection, and (3) injection of frozen medium as a control. Mice were monitored by slit lamp<span> and underwent anterior segment optical coherence tomography (ASOCT). Following euthanasia, the corneas were further evaluated by histology and </span></span></span>immunostaining.</p></div><div><h3>Results</h3><p><span>hBM-MSC injection successfully healed epithelial defects<span><span><span> regardless of the delivery route (P < 0.001). However, intrastromal injection was superior to subconjunctival injection in reducing defect area (P = 0.001). Intrastromal injection of hBM-MSCs also significantly reduced </span>corneal opacity and </span>neovascularization<span> and improved ASOCT parameters compared to subconjunctival injection or no treatment<span> (P < 0.001, P = 0.003, and P < 0.001, respectively). Although both of the treatment groups were positive for CK12 and had reduced levels of MUC5AC compared to the control, CK12 staining was stronger in the intrastromal group compared to the subconjunctival group. Also, persistency of MSCs was confirmed by </span></span></span></span><em>in vivo</em> (up to 2 weeks) and <em>in vitro</em> assessments (up to 4 weeks).</p></div><div><h3>Conclusions</h3><p>Although the injection of hBM-MSC using both intrastromal and subconjunctival methods improve wound healing and reduce neovascularization and opacity, the intrastromal approach is superior in terms of corneal healing.</p></div>\",\"PeriodicalId\":54691,\"journal\":{\"name\":\"Ocular Surface\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ocular Surface\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S154201242300126X\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ocular Surface","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S154201242300126X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Intrastromal versus subconjunctival injection of mesenchymal stem/stromal cells for promoting corneal repair
Purpose
Different approaches to delivery of mesenchymal stem/stromal cells (MSCs) for ameliorating corneal injuries have been investigated. This study was aimed to compare the efficacy of intrastromal and subconjunctival injection of human bone marrow-derived MSCs (hBM-MSCs) in a corneal epithelial injury model.
Methods
Twenty-four C57BL/6J mice underwent total corneal and limbal epithelial debridement. Then, the mice were divided into three different groups: (1) intrastromal hBM-MSCs injection, (2) subconjunctival hBM-MSCs injection, and (3) injection of frozen medium as a control. Mice were monitored by slit lamp and underwent anterior segment optical coherence tomography (ASOCT). Following euthanasia, the corneas were further evaluated by histology and immunostaining.
Results
hBM-MSC injection successfully healed epithelial defects regardless of the delivery route (P < 0.001). However, intrastromal injection was superior to subconjunctival injection in reducing defect area (P = 0.001). Intrastromal injection of hBM-MSCs also significantly reduced corneal opacity and neovascularization and improved ASOCT parameters compared to subconjunctival injection or no treatment (P < 0.001, P = 0.003, and P < 0.001, respectively). Although both of the treatment groups were positive for CK12 and had reduced levels of MUC5AC compared to the control, CK12 staining was stronger in the intrastromal group compared to the subconjunctival group. Also, persistency of MSCs was confirmed by in vivo (up to 2 weeks) and in vitro assessments (up to 4 weeks).
Conclusions
Although the injection of hBM-MSC using both intrastromal and subconjunctival methods improve wound healing and reduce neovascularization and opacity, the intrastromal approach is superior in terms of corneal healing.
期刊介绍:
The Ocular Surface, a quarterly, a peer-reviewed journal, is an authoritative resource that integrates and interprets major findings in diverse fields related to the ocular surface, including ophthalmology, optometry, genetics, molecular biology, pharmacology, immunology, infectious disease, and epidemiology. Its critical review articles cover the most current knowledge on medical and surgical management of ocular surface pathology, new understandings of ocular surface physiology, the meaning of recent discoveries on how the ocular surface responds to injury and disease, and updates on drug and device development. The journal also publishes select original research reports and articles describing cutting-edge techniques and technology in the field.
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