Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice

Abstract Background Retina diseases may lead to blindness as they often afflict both eyes. Stem cell transplantation into the affected eye(s) is a promising therapeutic strategy for certain retinal diseases. Human peripheral blood mononuclear cells (hPBMCs) are a good source of stem cells, but it is...

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Main Authors: Jianfa Huang, Bikun Xian, Yuting Peng, Baozhu Zeng, Weihua Li, Zhiquan Li, Yaojue Xie, Minglei Zhao, Hening Zhang, Minyi Zhou, Huan Yu, Peixin Wu, Xing Liu, Bing Huang
Format: Article
Language:English
Published: BMC 2021-03-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-021-02180-5
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author Jianfa Huang
Bikun Xian
Yuting Peng
Baozhu Zeng
Weihua Li
Zhiquan Li
Yaojue Xie
Minglei Zhao
Hening Zhang
Minyi Zhou
Huan Yu
Peixin Wu
Xing Liu
Bing Huang
author_facet Jianfa Huang
Bikun Xian
Yuting Peng
Baozhu Zeng
Weihua Li
Zhiquan Li
Yaojue Xie
Minglei Zhao
Hening Zhang
Minyi Zhou
Huan Yu
Peixin Wu
Xing Liu
Bing Huang
author_sort Jianfa Huang
collection DOAJ
description Abstract Background Retina diseases may lead to blindness as they often afflict both eyes. Stem cell transplantation into the affected eye(s) is a promising therapeutic strategy for certain retinal diseases. Human peripheral blood mononuclear cells (hPBMCs) are a good source of stem cells, but it is unclear whether pre-induced hPBMCs can migrate from the injected eye to the contralateral eye for bilateral treatment. We examine the possibility of bilateral cell transplantation from unilateral cell injection. Methods One hundred and sixty-one 3-month-old retinal degeneration 1 (rd1) mice were divided randomly into 3 groups: an untreated group (n = 45), a control group receiving serum-free Dulbecco’s modified Eagle’s medium (DMEM) injection into the right subretina (n = 45), and a treatment group receiving injection of pre-induced hPBMCs into the right subretina (n = 71). Both eyes were examined by full-field electroretinogram (ERG), immunofluorescence, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR) at 1 and 3 months post-injection. Results At both 1 and 3 months post-injection, labeled pre-induced hPBMCs were observed in the retinal inner nuclear layer of the contralateral (left untreated) eye as well as the treated eye as evidenced by immunofluorescence staining for a human antigen. Flow cytometry of fluorescently label cells and qRT-PCR of hPBMCs genes confirmed that transplanted hPBMCs migrated from the treated to the contralateral untreated eye and remained viable for up to 3 months. Further, full-field ERG showed clear light-evoked a and b waves in both treated and untreated eyes at 3 months post-transplantation. Labeled pre-induced hPBMCs were also observed in the contralateral optic nerve but not in the blood circulation, suggesting migration via the optic chiasm. Conclusion It may be possible to treat binocular eye diseases by unilateral stem cell injection. Graphical abstract
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spelling doaj.art-3730b92a586343dfbdcb7618c0bfe4402022-12-21T22:26:49ZengBMCStem Cell Research & Therapy1757-65122021-03-0112111310.1186/s13287-021-02180-5Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in miceJianfa Huang0Bikun Xian1Yuting Peng2Baozhu Zeng3Weihua Li4Zhiquan Li5Yaojue Xie6Minglei Zhao7Hening Zhang8Minyi Zhou9Huan Yu10Peixin Wu11Xing Liu12Bing Huang13State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityAbstract Background Retina diseases may lead to blindness as they often afflict both eyes. Stem cell transplantation into the affected eye(s) is a promising therapeutic strategy for certain retinal diseases. Human peripheral blood mononuclear cells (hPBMCs) are a good source of stem cells, but it is unclear whether pre-induced hPBMCs can migrate from the injected eye to the contralateral eye for bilateral treatment. We examine the possibility of bilateral cell transplantation from unilateral cell injection. Methods One hundred and sixty-one 3-month-old retinal degeneration 1 (rd1) mice were divided randomly into 3 groups: an untreated group (n = 45), a control group receiving serum-free Dulbecco’s modified Eagle’s medium (DMEM) injection into the right subretina (n = 45), and a treatment group receiving injection of pre-induced hPBMCs into the right subretina (n = 71). Both eyes were examined by full-field electroretinogram (ERG), immunofluorescence, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR) at 1 and 3 months post-injection. Results At both 1 and 3 months post-injection, labeled pre-induced hPBMCs were observed in the retinal inner nuclear layer of the contralateral (left untreated) eye as well as the treated eye as evidenced by immunofluorescence staining for a human antigen. Flow cytometry of fluorescently label cells and qRT-PCR of hPBMCs genes confirmed that transplanted hPBMCs migrated from the treated to the contralateral untreated eye and remained viable for up to 3 months. Further, full-field ERG showed clear light-evoked a and b waves in both treated and untreated eyes at 3 months post-transplantation. Labeled pre-induced hPBMCs were also observed in the contralateral optic nerve but not in the blood circulation, suggesting migration via the optic chiasm. Conclusion It may be possible to treat binocular eye diseases by unilateral stem cell injection. Graphical abstracthttps://doi.org/10.1186/s13287-021-02180-5Human peripheral blood mononuclear cellsStem cellsCell therapyMigrationOcular diseases
spellingShingle Jianfa Huang
Bikun Xian
Yuting Peng
Baozhu Zeng
Weihua Li
Zhiquan Li
Yaojue Xie
Minglei Zhao
Hening Zhang
Minyi Zhou
Huan Yu
Peixin Wu
Xing Liu
Bing Huang
Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice
Stem Cell Research & Therapy
Human peripheral blood mononuclear cells
Stem cells
Cell therapy
Migration
Ocular diseases
title Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice
title_full Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice
title_fullStr Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice
title_full_unstemmed Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice
title_short Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice
title_sort migration of pre induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice
topic Human peripheral blood mononuclear cells
Stem cells
Cell therapy
Migration
Ocular diseases
url https://doi.org/10.1186/s13287-021-02180-5
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