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通过可注射的微流体模板微凝胶移植人胚胎干细胞衍生的视网膜色素上皮细胞用于视网膜再生。

Transplantation of human embryonic stem cell-derived retinal pigment epithelial cells via injectable microfluidic-templated microgels for retinal regeneration.

作者信息

Wei Ying, Ma Cong, An Chuanfeng, Zhang Yujie, Zhang Haoyue, Li Qiyou, Kong Li, Wang Huanan, Ma Xiang

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116014, China.

MOE Key Laboratory of Bio-Intelligent Manufacturing, Dalian Key Laboratory of Artificial Organ and Regenerative Medicine, School of Bioengineering, Dalian University of Technology, Dalian, 116024, China.

出版信息

Mater Today Bio. 2025 May 23;32:101880. doi: 10.1016/j.mtbio.2025.101880. eCollection 2025 Jun.


DOI:10.1016/j.mtbio.2025.101880
PMID:40520565
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12163166/
Abstract

Retinal pigment epithelial (RPE) cells are specialized neural cells crucial for vision, while human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells hold great potential as a viable cell source for treating retinal degenerative diseases like retinitis pigmentosa (RP). However, the transplantation efficiency and viability of hESC-RPE cell suspensions are relatively low due to detrimental shear-force during operations and host immune-clearance. We herein develop an alternative transplantation strategy with the aid of a microfluidic-templating microgel cell carrier to achieve substantially enhanced loading and delivery efficiency of hESC-RPE cells, thereby promoting visual function recovery after subretinal injection in the RP model Royal College of Surgeons (RCS) rats. Specifically, injectable monodispersed microgels consisting of gelatin-methacryloyl/Hyaluronic acid-methacryloyl core coated with fibrin shell (denoted as Fib@GHMS) were fabricated in a high-throughput and controllable manner, facilitating the adhesion and proliferation of hESC-RPE cells. RCS rats treated with microcarriers showed significantly improved visual function, evidenced by increased B-wave amplitudes and the preservation of the inner nuclear layer at 8 weeks post-surgery. In conclusion, our innovative delivery system Fib@GHMS for hESC-RPE cell transplantation presents a potential therapeutic graft for retinal tissue engineering. It may open a new avenue for clinical transplantation of minimally invasive cell-based treatments in retinal degenerative diseases.

摘要

视网膜色素上皮(RPE)细胞是对视觉至关重要的特殊神经细胞,而人胚胎干细胞衍生的视网膜色素上皮(hESC-RPE)细胞作为治疗视网膜色素变性(RP)等视网膜退行性疾病的可行细胞来源具有巨大潜力。然而,由于操作过程中有害的剪切力和宿主免疫清除作用,hESC-RPE细胞悬液的移植效率和存活率相对较低。我们在此借助微流控模板微凝胶细胞载体开发了一种替代移植策略,以显著提高hESC-RPE细胞的负载和递送效率,从而促进皇家外科学院(RCS)大鼠RP模型视网膜下注射后视觉功能的恢复。具体而言,以高通量和可控的方式制备了由明胶-甲基丙烯酰/透明质酸-甲基丙烯酰核心包裹纤维蛋白壳组成的可注射单分散微凝胶(记为Fib@GHMS),促进了hESC-RPE细胞的黏附和增殖。用微载体治疗的RCS大鼠视觉功能显著改善,术后8周B波振幅增加和内核层保留证明了这一点。总之,我们用于hESC-RPE细胞移植的创新递送系统Fib@GHMS为视网膜组织工程提供了一种潜在的治疗移植物。它可能为视网膜退行性疾病基于细胞的微创治疗的临床移植开辟一条新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/e9cf841962cc/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/f2ebc4256e2b/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/ce865b4bed73/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/fe064e05cba5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/200742c1ec29/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/d9011b05807e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/3c366ca62ca5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/b8d7da2482da/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/e9cf841962cc/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/f2ebc4256e2b/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/ce865b4bed73/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/fe064e05cba5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/200742c1ec29/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/d9011b05807e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/3c366ca62ca5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/b8d7da2482da/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ff/12163166/e9cf841962cc/gr7.jpg

相似文献

[1]
Transplantation of human embryonic stem cell-derived retinal pigment epithelial cells via injectable microfluidic-templated microgels for retinal regeneration.

Mater Today Bio. 2025-5-23

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Retinal Pigment Epithelium Transplantation in Retinal Disease: Clinical Trial Development, Challenges, and Future Directions.

Biomolecules. 2025-8-15

本文引用的文献

[1]
Adaptive Optics Optical Coherence Tomography Analysis of Induced Pluripotent Stem Cell-Derived Retinal Organoid Transplantation in Retinitis Pigmentosa.

Cureus. 2024-7-19

[2]
Cell volume regulation modulates macrophage-related inflammatory responses via JAK/STAT signaling pathways.

Acta Biomater. 2024-9-15

[3]
Recent Progress in Retinal Pigment Epithelium Cell-Based Therapy for Retinal Disease.

Stem Cells Transl Med. 2024-4-15

[4]
Single-cell transcriptomics reveals maturation of transplanted stem cell-derived retinal pigment epithelial cells toward native state.

Proc Natl Acad Sci U S A. 2023-6-27

[5]
Structural and biological engineering of 3D hydrogels for wound healing.

Bioact Mater. 2022-12-23

[6]
Hydrogels to Support Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells.

Brain Sci. 2022-11-25

[7]
Electroretinogram (ERG) to Evaluate the Retina in Cases of Retinitis Pigmentosa (RP).

Methods Mol Biol. 2023

[8]
Injectable composite hydrogels encapsulating gelatin methacryloyl/chitosan microspheres as ARPE-19 cell transplantation carriers.

Biomater Sci. 2022-12-20

[9]
Microfluidic-templated cell-laden microgels fabricated using phototriggered imine-crosslinking as injectable and adaptable granular gels for bone regeneration.

Acta Biomater. 2023-2

[10]
Fabrication and Evaluation of Gellan Gum/Hyaluronic Acid Hydrogel for Retinal Tissue Engineering Biomaterial and the Influence of Substrate Stress Relaxation on Retinal Pigment Epithelial Cells.

Molecules. 2022-8-27

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