Yesterday, a breaking news in the stem cell field came from a case report published in the New England Journal of Medicine (a respected journal in medical research) (http://www.nejm.org/doi/full/10.1056/NEJMoa1609583?query=featured_home).
What is probably the most intriguing about this case report from a stem cell clinic, that had a clinical trial submitted to the FDA and subsequently withdrawn in 2015 (https://clinicaltrials.gov/ct2/show/NCT02024269?term=NCT02024269&rank=1).
This case report focuses on three patients, elderly patients (70+) and all three suffering from age-related macular degeneration (AMD).
They all three being injected with mesenchymal stem cells. For those not familiar with stem cells, stem cells comes into different flavors depending on their origin and potency abilities. The most pluripotent type of stem cells are the embryonic stem cells (hESCs) that are derived from embryos. Following in their pluripotency comes in the induced pluripotent stem cells (iPSCs). Unlike hESCs, iPSCs are reprogrammed somatic cells (usually skin fibroblasts). Then we have bone marrow stem cells (from bone marrow) that have a narrower pluripotency but proven efficacious for treating patients with leukemia. Finally we have the mesenchymal stem cells (MSCs) obtained from the stream fraction of adipose tissue. Usually these cells are obtained by liposuction and isolated from the fat tissue via defined protocols.
Now this last type of cells has a certain classification that allows to use a loophole. In order to conduct a clinical trial, you have to submit an investigative new drug (IND) application to the Food & Drug Administration to show evidence of safety and efficacy from pre-clinical studies. These are safeguards that ensure patients and medical researchers enrolled in such trials.
Now, when you are dealing with MSCs, these stem cell “clinics” can exploit some loopholes and apply for a non-IND application if your trial follows two criteria: it is an autologous procedure (you are injecting cells from yourself back into your body) and there is no procedures that modify the material used (in that case, the purification steps are not altering the MSCs identity and function). In addition, these trials have to be done without any financial link. In academic institutions, you neither ask the patient to pay for the clinical trial nor provide the patient with a financial compensation (only a possible therapeutic outcome, if the treatment work). In this case reports, all patients paid $5000 to that clinic. it is also important to note a certain level of deception from the stem cell clinic as this registration at the ClinicalTrials.gov website appeared to these patients as a clinical trial were it was not. It is even mentioned by the authors of this case report that none of the consent form signed by these patients displayed “clinical trial”.
There is also report in the consent form that the patient were informed of the risk of blindness and were requesting to have the procedure done in both eyes.
These patients rapidly developed post-operative complication including retinal detachment, increased ocular pressure and hemorrhagic events, such complications were not taken care by the clinic involved in the stem cell procedure and were done in eye clinics in patients domicile.
By coincidence, NEJM also published another case report of the use of stem cells in AMD in a clinical trial in Japan (http://www.nejm.org/doi/full/10.1056/NEJMoa1608368?query=featured_home). This procedure was done using iPSCs from patients and derived into retinal pigmented epithelial cells (RPEs). These cells are lining the outer side of the retina and serve as a barrier for protecting the retinal neurons involved in vision. This is the famous “iPSC clinical trial” from Takahashi and colleagues that had to be halted due to some safety issues that were corrected (https://ipscell.com/2016/06/good-stem-cell-news-as-takahashi-ips-cell-trial-to-resume/).
So far, the encouraging part is the absence of post-operative complication and graft rejection and the patient showed an improvement in her vision.Yet, this is a single report and the authors were also very cautious about to make overstating conclusion.
These two cases report should inform into two things: we are making little steps but confident steps in stem cell based therapies but it is also important to raise awareness and vigilance about the methods of some stem cell clinics making unrealistic claims of stem cell therapies or posing as clinical trial center.
My recommendation is if you decide to jump into a clinical trial is to verify the affiliation of the center (avoid any private firms and check the credentials of any institution supporting this trial), ask your doctor to help you read through the consent form and never ever be asked to pay for the procedure. The trial is funded by research grants, if it is requested that you cover the expenses of such procedures run away!