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. Ongoing investigations of tissue engineering researchers in Sweden
In a wake of Paolo Macchiarini’s scandal, Leonid Schneider continues to investigate research misconduct cases in Sweden. His new blog post investigates issues in medical research, conducted by Suchitra Sumitran-Holgersson, from University of Gothenburg. Sumitran-Holgersson was involved in clinical transplantation of tissue engineered trachea and blood vessels. Swedish hospital, where one of trachea transplant patients died after surgery, investigates the ethical side of the case. In the same time, issues with Sumitran-Holgersson’s scientific publications are discussed at PubPeer. She already had one retraction in the past. Yet another blog post connects Macchiarini’s and Sumitran-Holgersson research misconducts:
And the big thundercloud hovering over the whole affair is of course the fact that the same scientist was from 2008 to 2010 the object of a large investigation for misconduct at KI. She was convicted, fired and her grants were frozen. But after a reinvestigation she was later exonerated. Some have called her sentencing a “gross miscarriage of justice”; others say the opposite, that the exoneration was a scandal. Suffice to say; in the world of Swedish medical science it was a very big deal. The affair is still echoing in the halls of both KI and GU. Regardless of which side is right, she has been at GU now for a number of years, done what seems to be very successful work, but which is now being seriously questioned.
2. More investigations of stem cell researchers
Retraction Watch posted about investigation of stem cell researcher from Spain.
A promising early career researcher has been dismissed from her post at the National Center for Cardiovascular Research (CNIC) in Spain, following “an alleged ongoing fraud,” according to El Pais.
We don’t know what exactly the internal investigation into Susana González’s work found; El Pais relied on anonymous sources, and the CNIC confirmed only that they dismissed her on February 29th. There are allegations against her work on PubPeer, but we don’t know what role those played in the investigation.
Yet another stem cell researcher, Chris Fasano has been “placed on administrative leave” due to investigation of his publications. In this case, investigation was clearly triggered by criticism of his papers on PubPeer. Fasano has at least 5 papers discussions on PubPeer. He responded to all of them and admitted some errors.
3. CRISPR interference for gene silencing in stem cells
Researchers from Gladstone Institutes described a method for specific and reversible gene silencing in iPS cells. The used modified CRISPR, called CRISPR interference (described for the first time in 2013), to reversibly silence genes in iPS cells and their progeny. From press release:
“We were amazed by the dramatic difference in performance between the two systems,” said senior author Bruce Conklin, MD, a senior investigator in the Gladstone Institute of Cardiovascular Disease and Roddenberry Stem Cell Center at Gladstone. “We thought that permanently cutting the genome would be the more effective way to silence a gene, but in fact, CRISPRi is so precise and binds so tightly to the genome that it is actually a better way to silence a gene.”
In the study, the researchers compared how well CRISPRi and CRISPR-Cas9 silenced a particular gene that controls iPSC pluripotency—the capability of iPSCs to turn into multiple cell types. They discovered that CRISPRi was much more efficient than CRISPR-Cas9: in more than 95% of the cells created using CRISPRi, the target gene was silenced, compared with only 60-70% of cells grown from CRISPR-Cas9. CRISPRi also did not cause any off-target changes in gene expression, like undesired insertions or deletions to the cell’s genome, which is a concern with CRISPR-Cas9.
4. Lens regeneration in cataracts
The paper, published this week in Nature, made a big buzz in mass media. This is a very rare case, when Nature ok’d publication of animal studies with clinical trial results. Unlike traditional surgery of cataracts, refined technique led to preservation of lens stem cells and successful regeneration. No stem cells were transplanted in this case, surgery alone did “all magic”.
… we show that a new minimally invasive cataract surgery method preserves the integrity of the lens capsule and associated LECs, facilitating functional lens regeneration in animals and humans. In addition to achieving lens regeneration in patients with congenital cataracts, our method also increased visual axis transparency and decreased the rate of complications.
Our method resulted in visual axis transparency in >95% of cataractous eyes in infants, a much higher percentage than that obtained by traditional surgery.
5. Durability of response in TiGenix stem cell trial for Crohn’s disease
Belgian company TiGenix, which reported positive results of Phase 3 trial in Crohn’s disease last year, updated on 1-year durability of responses. In this trial, allogeneic expanded adipose-derived stem cells were injected in fistulas, caused by progression of Crohn’s disease.
54.2% of patients treated with Cx601 achieved combined remission at week 52 compared to 37.1% in the placebo arm. 75.0% of Cx601 treated patients who achieved combined remission at week 24 remained in combined remission at week 52 compared to only 55.9% in the placebo arm. The results confirm the favorable safety and tolerability profile of Cx601 already reported at week 24.
Not bad, but I’m still puzzled by high placebo effect. I hope, TiGenix will get market approval in Europe this year.
6. Fresh reviews:
Reverse Engineering Human Pathophysiology with Organs-on-Chips (Cell)
Targeted genome engineering using designer nucleases (Stem Cell Res)
Empowering Adult Stem Cells for Myocardial Regeneration V2.0 (Circ Res)
7. New methods and protocols:
3D bioprinting of thick vascularized tissues (PNAS)
In vivo reprogramming reactive glia into iPSCs to produce new neurons (Sci Rep)
Characterization of MSCs and fibrochondrocytes in 3D co-culture (Stem Cell Res Ther)
Influence of aging on the quantity and quality of human cardiac stem cells (Sci Rep)