Human embryonic stem cells: early hints on safety and effi cacy (2012)

1report the fi rst clinical experience of patients treated with cells derived from human embryonic stem cells (hESCs). A patient with Stargardt’s macular dystrophy, the most common paediatric macular degeneration, and a patient with dry age-related macular degeneration, the leading cause of blindness in the developed world, each received a subretinal injection of hESC-derived retinal pigment epithelium (RPE). Both disorders are at present thought untreatable and are associated with degeneration of the RPE, which leads to photoreceptor loss and progressive vision defi ciency. Schwartz and colleagues diff erentiated the hESCs into greater than 99% pure RPE in culture; they injected 50 000 retinal epithelium cells into the subretinal space of one eye in each patient. The immunosuppression regimen included low-dose tacrolimus and mycophenolate mofetil. The investigators did not note any retinal detach ment, hyperproliferation, abnormal growth, intraocular infl ammation, or teratoma formation during the 4-month follow-up period. Anatomical evidence of the injected cells was diffi cult to confi rm in the patient with age-related macular degeneration, but was present in the patient with Stargardt’s macular dystrophy. Schwartz and colleagues noted functional visual improvements in both patients. The patient with age-related macular degeneration showed functional improvements including best corrected visual acuity changes from 21 letters in the visual acuity chart (20/500 vision for the patient, with 20/20 being perfect vision) at baseline to 28 letters (20/320), which remained stable after 6 weeks. At baseline, the central vision of the patient with Stargardt’s macular dystrophy was hand motions only. Best corrected visual acuity improved to counting fi ngers and seeing only one letter in the eye chart by week 2, and to a stable level of fi ve letters (20/800) after 4 weeks, with subjective improvement in colour vision, contrast, and dark adaptation in the treated eye. Schwartz and colleagues have realised the potential to use hESCs therapeutically in human beings. Their report is preliminary, in only two patients, and with a short-term follow-up; but the results are impressive— especially considering the progressive nature of both diseases. Also of importance is that the patients were part of a phase 1 safety study, and the lowest dose was not only safe but seems to be eff ective for the duration of the 4-month follow-up. The investigators appropriately maintain a cautionary tone, because it is still unclear whether any of the visual improvements recorded were due to the transplanted cells or to other factors, such as the immunosuppressive drugs. It is also possible that repeated treatments will be necessary. It might seem that we have waited too long to fi nally see hESCs in the clinic. However, this has been accomplished with incredible speed when it is considered that hESCs were fi rst isolated just 14 years ago. 2 To place the timeline in the correct perspective, the concept of treatment with cells can be traced to the 1800s. However, the fi rst use of stem cells for treatment did not happen until 1956, with the fi rst successful bonemarrow transplant between a related human donor and recipient. 3 Embryonic cells were fi rst derived from mice in 1981, 4 and James Thomson isolated and grew the fi rst stem cells from human embryos in 1998. 2