This week the Lancet published an article1 that has had a significant impact in the scientific community, in particular researchers interested in the potential of stem cells. Essentially, Robert Lanza's team at Advanced Cell Technology (ACT) has for the first time successfully completed a Phase I clinical trial using human embryonic stem cells (hESCs) in a therapeutic perspective. This technical breakthrough comes after more than 15 years of research on embryonic stem cells. However, it does not overshadow the significance of the ongoing clinical trial in Japan, which also deals with the eye and uses more recent iPS stem cells that do not require the destruction of embryos.
A breakthrough …
This report follows up a study carried out two years ago on two patients by the authors of this hESC clinical trial. Since then pending a complete series they had published nothing: this week's publication concerns 19 patients. The study primarily reports the following results:
no side effects, cancer, or rejection of the injected retinal cells - it may be noted that this result is compelling without necessarily coming as a surprise, as it concerns insertions in a site that cannot produce an immune response;
an improvement after six months in half of the cases: in 4 of 9 patients affected by AMD;
also an improvement in half of the Stargardt’s MD cases, compared to the untreated eye;
some secondary problems related to the surgery itself;
the development of a cataract in four cases.
Accordingly, the results are convincing, but the observed improvements affect only half the patients and are minimal. This is partly due to the fact that this is a phase I trial implying relatively low doses of cells before its optimization in potentially more significant Phase II trials.
… Hence the need for more nuanced explanations
For Paul Knoepfler the world-renowned expert, even though it is a very encouraging study for all research on stem cells, these results are somewhat "surprising in terms of efficacy." For him, it could be that the observed benefits may not be directly linked to the transplanted cells themselves. Certainly, "the leading cause of visual impairment from macular degeneration is usually not due to a loss of retinal pigment epithelium cells, but rather to that of photoreceptor cells. So, how could transplantation of this epithelium [recreated from hESCs] (and for the most part at relatively low cell doses) potentially improve vision? The working theory seems to be that these cells might help remaining photoreceptors stay alive, healthier, and perhaps more properly functional."
In addition, Jennifer Couzin Frankel and Kelly Servick agree with this suggestion in the journal of reference Science and add that "Lanza is careful to point out that for ethical reasons, the study had no control group that received the surgery without the transplanted cells."
A breakthrough in circumstances for hESCs that does not eclipse the dynamics of iPS cells
This first convincing test for hESCs comes after 16 years of global research on these cells [hESCs were discovered in 1998 by James Thomson; Mouse ES cells were isolated in 1981] and their potential therapeutic applications. IPS cells produced by the Nobel laureate Professor Yamanaka only 7 years ago have already reached this same stage in clinical trials.
Furthermore, if the Lanza team trial is noteworthy, it is currently relatively isolated; at least 10 clinical trials on the therapeutic use of iPS cells await approval.