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. Advances in growing human embryos in vitro and 14-days rule debate
This week researchers from Rockefeller University and U of Cambridge reported improved in vitro system for culture of early human embryos. By letting embryos to self-organize in culture, researchers able to maintain them up to 13 days. This is the longest culture maintenance of normal human embryos, ever reported before. Since many countries have a ban on in vitro manipulations with human embryos after 14 days of age, these studies triggered a new wave of debate on so-called “14-days rule”. You can read great coverage of this discussion by Nature (here and here), STAT and Science magazine.
Revisiting the 14-day rule might tempt people to try to rationalize or attack the philosophical coherence of the limit as an ethical tenet grounded in biological facts. This misconstrues the restriction. The 14-day rule was never intended to be a bright line denoting the onset of moral status in human embryos. Rather, it is a public-policy tool designed to carve out a space for scientific inquiry and simultaneously show respect for the diverse views on human-embryo research.
2. Gene therapy of rare brain disease – conference report
Science magazine reported about presentation of preliminary results from gene therapy of rare brain disease on American Society of Gene and Cell Therapy annual meeting:
… all but one of 17 boys with adrenoleukodystrophy (ALD) remained relatively healthy for up to 2 years after having an engineered virus deliver into their cells a gene to replenish a missing protein needed by the brain. The results, which expand on an earlier pilot study, bring this ALD therapy one step closer to the clinic.
94% efficacy is very impressive! The study is sponsored by US-based cell-gene therapy company Bluebird Bio. There was no press release by company.
3. The first approved gene therapy drug in Europe stuck in clinical adoption
Antonio Regalado of MIT Tech Review wrote a provocative piece on Glybera – the world’s most expensive drug. Gene therapy Glybera was approved in Europe in 2012 and since that was only used once. The reason – a price tag of ~$1M Euro. He interviewed physician from Germany, who prescribed Glybera for the first time:
But when the Berlin physician Elisabeth Steinhagen-Thiessen wanted to give a patient Glybera last fall, it wasn’t so easy. She says she had to prepare a submission as thick as “a thesis” for German regulators and then personally call the CEO of DAK, one of Germany’s large sickness funds, or insurers, to ask him to pay the $1 million price tag.
Last September, she gave 40 injections to the muscles of a 43-year-old woman with an ultra-rare disease called lipoprotein lipase deficiency. Such patients don’t process fat correctly. “You draw blood and you are astonished, there is no red blood, it’s cream,” Steinhagen-Thiessen says. One symptom is debilitating abdominal pain. Her patient had been hospitalized more than 40 times.
A dose of Glybera contains trillions of viruses harboring correct copies of the lipoprotein lipase gene. And Steinhagen-Thiessen says the treatment, at Charite Hospital in Berlin, was a success. The woman hasn’t been back to the emergency room since the treatment and is now “living like you and me.”
Very interesting piece, highly recommended!
Also read Antonio’s piece on soon-to-be approved another gene therapy in Europe.
4. Fetal tissue transplantation in Parkinson’s brain – a quarter of a century outcome
Researchers from Sweden, who performed the first fetal neural tissue transplantations in Parkinson’s disease about 25 years ago, reported very interesting pathology case. They described histopathological findings on autopsy material, obtained from unique patient, who underwent procedure 24 years ago:
The patient enjoyed major clinical benefits for at least a decade after transplantation. After a quarter of a century, complete graft-derived dopaminergic reinnervation was still evident in the transplanted putamen. α-Synuclein–positive inclusions, some with the appearance of typical Lewy bodies, were present in 11–12% of the grafted dopaminergic neurons, reflecting spread of pathology from the host brain to the transplant. The clinical improvements were gradually lost from 14 y posttransplantation, indicating that even extensive graft-derived dopaminergic reinnervation loses its efficacy in a severely degenerating brain.
5. The future of senolytic therapy
Senolytic therapy is elimination or altering of senescent cells to achieve tissue regeneration and/or anti-aging effect. Nick Dragojlovic wrote a nice brief overview of senolytic therapy on the Signals blog:
The race is on, and at least two biotechnology companies have been founded to tackle the problem: Oisin Biotechnologies, which is pursuing an innovative gene therapy approach; and, UNITY Biotechnology, a company backed by the Mayo Clinic and ARCH Venture Partners that has leading senescent cell researchers like Judith Campisi as advisors. Other companies are sure to follow in short order now that senescent cells have been demonstrated in an animal model to be a promising target for regenerative medicine. It may take a number of years for senolytic drugs to make their way from animal models to the clinic, but when they do become available, they have the potential to be transformative.
Turns out that the profiles between fresh and cryopreserved MSCs did not differ much. In fact, the profiles of fresh and cryopreserved MSCs from the same donor were more similar to each other than those of fresh MSCs that were obtained from different donors. Less than 300 genes were differently expressed, up to only 10fold. Compare that to the over 2,000 genes that were up to 720fold differently expressed between fresh mesenchymal stem cells and those located in murine lung tissue!
7. Mesenchymal stromal cells enhance tumor growth via tumor-derived exosomes
One of potential mechanisms of tumor growth promotion by mesenchymal stromal cells was recently described by researchers from China. Exosomes, released by tumor endow MSCs with ability to enhance tumor growth:
We report here a critical role of tumour cell-derived exosomes in endowing bone marrow-derived MSCs (BM-MSCs) with a tumour-favourable phenotype. Tumour cell-derived exosomes affected neither the growth factor production nor the immunosuppressive property of MSCs; rather, they endowed MSCs with a strong ability to promote macrophage infiltration into B16-F0 melanoma or EL-4 lymphoma.
8. New methods and protocols:
Review: Modeling pancreatic cancer with organoids (Trends in Cancer)
mTORC1 inhibition enhances human pluripotent stem cells differentiation toward blood progenitors (Stem Cell Rep)
Propagation of nephron progenitors derived from embryos and pluripotent stem cells (Cell Rep)
Optimization of iPS cell generation from urine-derived cells (Stem Cell Rep)
Single factor hepatic reprogramming facilitated by small molecules (Cell Rep)