Article

Embryonic stem cell trials for macular degeneration: A preliminary report

Jules Stein Eye Institute Retina Division, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
The Lancet (Impact Factor: 45.22). 02/2012; 379(9817):713-20. DOI: 10.1016/S0140-6736(12)60028-2
Source: PubMed

ABSTRACT

It has been 13 years since the discovery of human embryonic stem cells (hESCs). Our report provides the first description of hESC-derived cells transplanted into human patients.
We started two prospective clinical studies to establish the safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium (RPE) in patients with Stargardt's macular dystrophy and dry age-related macular degeneration--the leading cause of blindness in the developed world. Preoperative and postoperative ophthalmic examinations included visual acuity, fluorescein angiography, optical coherence tomography, and visual field testing. These studies are registered with ClinicalTrials.gov, numbers NCT01345006 and NCT01344993.
Controlled hESC differentiation resulted in greater than 99% pure RPE. The cells displayed typical RPE behaviour and integrated into the host RPE layer forming mature quiescent monolayers after transplantation in animals. The stage of differentiation substantially affected attachment and survival of the cells in vitro after clinical formulation. Lightly pigmented cells attached and spread in a substantially greater proportion (>90%) than more darkly pigmented cells after culture. After surgery, structural evidence confirmed cells had attached and continued to persist during our study. We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months. Although there is little agreement between investigators on visual endpoints in patients with low vision, it is encouraging that during the observation period neither patient lost vision. Best corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual acuity chart) in the study eye of the patient with Stargardt's macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular degeneration (from 21 ETDRS letters to 28).
The hESC-derived RPE cells showed no signs of hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection after 4 months. The future therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue.
Advanced Cell Technology.

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    • "NCT01345006) received subretinal injections of retinal pigment epithelium cells derived from human ESCs. Twenty-two months of follow up revealed that visual acuity improved significantly in 10 of 18 patients and to a lesser extent in the next seven patients (Schwartz et al. 2012). Currently, several other clinical trials based on PSC transplantation are ongoing (ClinicalTrials.gov; "
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    • "Please cite this article in press as: Plaza Reyes et al., Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model, Stem Cell Reports (2016), http://dx.doi.org/10.1016/j.stemcr.2015.11.008 ongoing clinical studies (Schwartz et al., 2012). Moreover, we demonstrate that suspension transplantations of rhLN-521-hESC-RPE integrate as polarized subretinal monolayers that rescue overlying photoreceptors from induced damage. "
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    • "The transplantation of RPE cells prevented the progression of photoreceptor and visual loss in various animal models. However, attempts to transplant new RPE cells into diseased eyes of human AMD patients have been challenging (Algvere et al., 1994, 1997, 1999; Binder et al., 2002, 2004, 2007; Tezel et al., 2007; Falkner-Radler et al., 2011; Schwartz et al., 2012), and only resulted in improved vision in a limited number of cases (Heller and Martin, 2014). "
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