Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration

Abstract

We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).

Stem cell therapies for retinal diseases: recapitulating development to replace degenerated cells

“…The first Phase I clinical trial of autologous iPSC-derived RPE sheets for wet AMD patients was launched by RIKEN (Rikagaku Kenkyusho Institute), Japan, in 2014. The investigators performed the surgery on the first patient in September 2014 and it was reported that the patient did not experience any serious side effects (Reardon and Cyranoski, 2014;Mandai et al, 2017). The study was put on hold because genetic mutations were found in cells from the second patient (https://www.newscientist.com/article/ dn27986/).…”

Zelltherapie am Augenhintergrund – gestern, heute, morgen

“…Nach wie vor ist die Studie des Riken Instituts in Japan die einzige, die bis dato iPSCs am Menschen angewandt hatte [33,37,40]. Sie musste allerdings 2015 nach der Behandlung einer AMD-Patientin abgebrochen werden, da die iPSC-abgeleiteten RPE-Zellen des zweiten Patienten die präklinischen Sicherheitstestungen nicht erfolgreich absolvieren konnten: Es traten Neumutationen im Rahmen der Zellkultivierung und -propagierung auf.…”

Safety of Neural Stem Cell Therapy for Traumatic Brain Injury

“…Due to lack of uniform standards across the globe and varying extent of regulations of the cell therapy approach adverse reaction cases have been reported to date [19][20][21]. Additional bad press for autologous stem cells came in 2017 [22,23] and the untimely termination of the Pathway Trial [24,25]. In contrast, NSCs from other unrelated sources have been found to be safe [18,24,[26][27][28].…”