2. Academic Validation
  3. Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox

Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox

  • J Biol Eng. 2024 Jan 16;18(1):7. doi: 10.1186/s13036-024-00405-8.
Wenxuan Wang # 1 2,  Tingting Yang # 1 2,  Sihui Chen 1 2,  Liying Liang 2,  Yingxin Wang 2,  Yin Ding 3,  Wei Xiong 4,  Xiuhong Ye 1 2,  Yonglong Guo 5,  Shuhao Shen 1 2,  Hang Chen 1 2,  Jiansu Chen 6 7 8
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • 2 Institute of Ophthalmology, Medical College, Jinan University, Guangzhou, China.
  • 3 The University of Hong Kong - Shenzhen Hospital, Shenzhen, China.
  • 4 Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.
  • 5 College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • 6 Institute of Ophthalmology, Medical College, Jinan University, Guangzhou, China. [email protected].
  • 7 Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China. [email protected].
  • 8 Aier Eye Institute, Changsha, Hunan, China. [email protected].
  • # Contributed equally.
PMID: 38229139 DOI: 10.1186/s13036-024-00405-8
Abstract

Background: Retinal pigment epithelium (RPE) cell therapy is a promising way to treat many retinal diseases. However, obtaining transplantable RPE cells is time-consuming and less effective. This study aimed to develop novel strategies for generating engineered RPE patches with physiological characteristics.

Results: Our findings revealed that RPE cells derived from human induced pluripotent stem cells (hiPSCs) successfully self-assembled into spheroids. The RPE spheroids treated with Y27632 and Repsox had increased expression of epithelial markers and RPE-specific genes, along with improved cell viability and barrier function. Transcriptome analysis indicated enhanced cell adhesion and extracellular matrix (ECM) organization in RPE spheroids. These RPE spheroids could be seeded and bioprinted on collagen vitrigel (CV) membranes to construct engineered RPE sheets. Circular RPE patches, obtained by trephining a specific section of the RPE sheet, exhibited abundant microvilli and pigment particles, as well as reduced proliferative capacity and enhanced maturation.

Conclusions: Our study suggests that the supplementation of small molecules and 3D spheroid culture, as well as the bioprinting technique, can be effective methods to promote RPE cultivation and construct engineered RPE sheets, which may support future clinical RPE cell therapy and the development of RPE models for research applications.

Keywords

Collagen vitrigel scaffold; ROCK; Retinal pigment epithelium; Spheroid; TGF-β; Tissue engineering.

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