Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night!
1. CRISPR clinical trial in China
Nature reported this week about the world’s first clinical trial, involved CRISPR gene edited cells. The trial is planning to start next month in China:
A team led by Lu You, an oncologist at Sichuan University’s West China Hospital in Chengdu, plans to start testing such cells in people with lung cancer next month. The clinical trial received ethical approval from the hospital’s review board on 6 July.
Lu’s team will extract immune cells called T cells from the blood of the enrolled patients, and then use CRISPR–Cas9 technology — which pairs a molecular guide able to identify specific genetic sequences on a chromosome with an enzyme that can snip the chromosome at that spot — to knock out a gene in the cells. The gene encodes a protein called PD-1 that normally acts as a check on the cell’s capacity to launch an immune response, to prevent it from attacking healthy cells.
Here is a link to the trial. A month ago, NIH RAC recommended similar trial in US, however its approval by FDA may take many months. China now is taking a lead in clinical use of CRISPR gene editing technology.
2. Results of stem cell therapy trial in ALS
Israeli company Brainstorm announced top line results of their Phase 2 clinical trial, assessing induced bone marrow mesenchymal stromal cells in patients with ALS. Importantly, this trial was designed as randomized, double-blinded and placebo-controlled. 48 patients were enrolled in 3 US centers. The study met primary end point – safety. The efficacy end points yielded mixed results at different time points. Based on functional score, used in ALS, cells-treated patients demonstrated clear benefit at 2 weeks post-therapy, which declined at later time points (8, 12 and 24 weeks):
At two weeks post treatment, 74% of NurOwn patients were responders, compared to 46% of placebo patients.
At eight weeks, the difference narrowed to where there was basically no difference in the response rates between NurOwn and placebo.
But at 12 weeks, 28% of NurOwn patients were still responders compared to just 8% of placebo patients. At 24 weeks, the end of the study, four NurOwn patients (11%) remained responders while all of the placebo patients had progressed. There were zero placebo responders.
3. Bioprinted tissue in predictive toxicology
Researchers from bioprinting company Organovo and BioPharma giant Roche, recently published a proof-of-principle study, demonstrating advantage of 3D printed patient-derived liver tissue over conventional methods in toxicology.
In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates.
They tested this system on Trovafloxacin (Trovan)- withdrawn drug with hepatotoxic potential. The toxicity of this drug was not identified in standard pre-clinical tests and it was approved in 1998.
Significance of this study nicely described in the Motley Fool:
Truvan was withdrawn from the market in Europe after multiple people died from liver failure after taking the drug. Since 1999, the antibiotic has only been available in the U.S. for emergency use. Rezulin’s story is similar. First approved by the FDA in 1997, Rezulin was taken off the market in 2000 after being linked to deaths resulting from liver failure.
In both cases, clinical studies failed to detect the potential for liver damage with the drugs. The end results were millions (and even billions) of dollars lost — and patient deaths.
Organovo hopes that studies like the one recently published will help drugmakers appreciate the value of 3D bioprinted tissues. Between 1990 and 2010, there were 39 drugs withdrawn from the market. Ten of those drugs caused liver damage, but the toxicity wasn’t picked up in testing. Another 13 drugs caused cardiovascular problems.
4. Stories from gene therapy trials
Antonio Regalado of MIT Tech Review and Ricki Lewis of DNA Science Blog this week posted some great patient stories from gene therapy trials. I’d highly recommend you to read them both:
Gene Therapy Trial Wrenches Families as One Child’s Death Saves Another (MIT Tech Review)
Hannah Has Her Gene Therapy for GAN: When Science Becomes Medicine (DNA Science Blog)
5. Adipose tissue serves as a niche for cancer stem cells
Research group, led by Craig Jordan recently demonstrated that adipose tissue serves as a niche for leukemic stem cells:
Here, we show that a subpopulation of leukemic stem cells (LSCs) can utilize gonadal adipose tissue (GAT) as a niche to support their metabolism and evade chemotherapy. In a mouse model of blast crisis chronic myeloid leukemia (CML), adipose-resident LSCs exhibit a pro-inflammatory phenotype and induce lipolysis in GAT. GAT lipolysis fuels fatty acid oxidation in LSCs, especially within a subpopulation expressing the fatty acid transporter CD36. CD36+ LSCs have unique metabolic properties, are strikingly enriched in AT, and are protected from chemotherapy by the GAT microenvironment.
6. Debate on naive pluripotency state
Rudolf Jaenisch group from MIT publishes a lot on naive pluripotency. One of their latest studies, published in Cell Stem Cell was disputed by another prominent stem cell researcher Jacob Hanna on PubMed Commons and PubPeer. More about Hanna – Jaenisch clash read on the Niche blog.