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28 March 2020 : Clinical Research  

Intravitreal Injection of Human Retinal Progenitor Cells for Treatment of Retinal Degeneration

Zhuoshi Wang12BC, Fei Gao3BC, Mingqi Zhang3DE, Yuqiang Zheng3F, Fenglei Zhang3F, Ling Xu2DE, Liu Cao1CD, Wei He12AG*

DOI: 10.12659/MSM.921184

Med Sci Monit 2020; 26:e921184

Abstract

BACKGROUND: Retinal degeneration causes irreversible blindness. Human retinal progenitor cells (hRPCs) have the potential to treat retinal diseases. The vitreous cavity is a relatively immune-privileged site that is suitable for stem cell transplantation in the treatment of retinal diseases. This study aimed to evaluate the therapeutic efficacy and safety of intravitreal injection of hRPCs in retinal degeneration therapy.

MATERIAL AND METHODS: hRPCs were primary-cultured and injected into the vitreous cavity of RCS rats. To determine whether hRPCs formed teratomas in immune-deficient mice, hRPCs at different passages were transplanted into BALB/c-nu mice. The visual function was detected by electroretinography recording. Changes in the outer nuclear layer (ONL) were analyzed by histological testing and cell counting. The protective mechanism was further assessed by cytokine antibody array.

RESULTS: Intravitreal transplantation of hRPCs maintained retinal function and preserved retinal morphology. Importantly, grafted cells in the vitreous cavity were well tolerated, with no adverse effects. Teratoma was not formed in BALB/c-nu mice after hRPCs transplantation. The number of hRPCs-injected eyes and thickness of ONL in the hRPCs-treated group were higher than those in the untreated group and HBSS injection group. The cytokine antibody array revealed that hRPCs expressed GDF-15, PDGF-AA, EGF, and NT-4.

CONCLUSIONS: Our findings show that intravitreal injection of hRPCs is effective and safe in protecting photoreceptor cells in RCS rats, but were no longer effective at 12 weeks after transplantation. Moreover, hRPCs released multiple neurotrophic factors that may be involved in treating retinal disease.

Keywords: Intravitreal Injections, Retinal Degeneration, Transplantation, Cell Self Renewal, Fetus, primary cell culture, Retina, Stem Cell Transplantation

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750