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

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

doi:10.1016/j.mtbio.2025.101880

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

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

Authors

Ying Wei¹, Cong Ma¹, Chuanfeng An^{2

3}, Yujie Zhang^{2

3}, Haoyue Zhang^{2

3}, Qiyou Li⁴, Li Kong⁵, Huanan Wang^{2

3}, Xiang Ma¹

Affiliations

¹ Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116014, China.
² 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.
³ State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, China.
⁴ Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.
⁵ Department of Histoembryology, Dalian Medical University, Dalian, 116044, China.

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.

Keywords: Cell transplantation; Cell-laden microgel; Injectable granular gel; Microfluidics; hESC-RPE.