Cell therapy with hiPSC-derived RPE cells and RPCs prevents visual function loss in a rat model of retinal degeneration

Anna Salas Torras, Anna Duarri, Laura Fontrodona Montals, Diana Ramírez Mora, Anna Badia Pérez, Helena Isla-Magrané, Barbara Ferreira-de-Souza, Miguel Angel Zapata, Ángel Raya, José García Arumí

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

Abstract

Photoreceptor loss is the principal cause of blindness in retinal degenerative diseases (RDDs). Whereas some therapies exist for early stages of RDDs, no effective treatment is currently available for later stages, and once photoreceptors are lost, the only option to rescue vision is cell transplantation. With the use of the Royal College of Surgeons (RCS) rat model of retinal degeneration, we sought to determine whether combined transplantation of human-induced pluripotent stem cell (hiPSC)-derived retinal precursor cells (RPCs) and retinal pigment epithelial (RPE) cells was superior to RPE or RPC transplantation alone in preserving retinal from degeneration. hiPSC-derived RPCs and RPE cells expressing (GFP) were transplanted into the subretinal space of rats. In vivo monitoring showed that grafted cells survived 12 weeks in the subretinal space, and rats treated with RPE + RPC therapy exhibited better conservation of the outer nuclear layer (ONL) and visual response than RPE-treated or RPC-treated rats. Transplanted RPE cells integrated in the host RPE layer, whereas RPC mostly remained in the subretinal space, although a limited number of cells integrated in the ONL. In conclusion, the combined transplantation of hiPSC-derived RPE and RPCs is a potentially superior therapeutic approach to protect retina from degeneration in RDDs. In this article, Anna Duarri and colleagues aim to develop a novel cell-based therapeutic approach to preserve retinal structure and function in retinal degenerative diseases caused by dysfunctional retinal pigment epithelium (RPE). Giving to the eye support of healthy RPE together with healthy retinal cells protects the retina from degeneration
Original languageEnglish
Pages (from-to)688-702
Number of pages15
JournalMolecular Therapy - Methods and Clinical Development
Volume20
DOIs
Publication statusPublished - 2021

Keywords

  • Cell therapy
  • Human-induced pluripotent stem cell
  • Retinal pigment epithelium
  • Photoreceptors
  • Retina degeneration
  • RCS rat
  • Regenerative medicine
  • RPE
  • IPSC
  • Subretinal injection

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