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!
Next week, I’ll live tweet from annual IBC Cell Therapy Bioprocessing conference. Follow me and the conference via hashtag #IBC_CTB14.
1. First patient received iPS cell-derived product in Japan
Friday, September 12, 2014 will become one of the most important landmarks in the history of stem cell research and therapy! This day, the first patient has received iPS cell-derived therapeutic product in Japan. A woman in her 70s, with macular degeneration underwent transplantation of retinal pigment epithelium cell sheets, derived from autologous iPS cells in RIKEN. David Cyranoski of Nature reports:
In a two-hour procedure starting at 14:20 local time today, a team of three eye specialists lead by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, transplanted a 1.3 by 3.0 millimetre sheet of retinal pigment epithelium cells into an eye of the Hyogo prefecture resident, who suffers from age-related macular degeneration.
The patient “took on all the risk that go with the treatment as well as the surgery”, Kurimoto said in a statement released by RIKEN. “I have deep respect for bravery she showed in resolving to go through with it.”
My warmest congratulations to Masayo Takahashi‘s team! Bravo Japan!
2. More STAP news
STAP saga is not over guys! A lot of things happened this week – very important things! First, Retraction Watch released reviews of STAP manuscripts, submitted to Science magazine and rejected by August 21, 2012. It triggered lively discussion. Second, day later, Science (via ScienceInsider) released reviews of STAP manuscript from Nature, dated April 04, 2013. Interestingly, all 3 Nature reviewers were negative and highlighted many concerns with manuscript. Nevertheless, editor made decision to “give it a try” and asked the authors to respond to reviewers comments, instead of rejecting it outright. About 8 month later, STAP paper was accepted! Ultimately, it was Nature’s editor decision. So, some anonymous sources leaked STAP papers reviews. There was no official statement from Science or Nature on this. Both leaks are making very compelling case for necessity of open peer-review:
Why did Nature have to re-review the same paper, without seeing the reviews at Science (apparently also rejected and possibly reviewed by Cell)? Would Nature really have published the STAP papers if the reviews were visible? Would there have been a scandal if the STAP papers were published along with the accompanying reviews that we just saw? Why are we as scientists wasting our time re-reviewing papers before and after publication? Why is there the misleading stamp of approval and quality when a paper is published in the fancy journals? And why do we always have to wonder if it’s in fact a good paper or one of the Arsenic/STAP-type “who knows why it’s published here?”
Third puzzle is update of STAP cell generation protocol from Vacanti’s lab. Despite the retractions of both STAP papers and related protocols and formal agreement of Vacanti for retraction, he continues to believe in existence of these elusive cells. From Nature News Blog:
“In recent months, our lab decided to re-explore the utility of a low pH solution containing ATP in generating STAP cells,” Vacanti writes in the revised protocol. “We found that while pH alone resulted in the generation of STAP cells, the use of a low pH solution containing ATP, dramatically increased the efficacy of this conversion.
“We made a significant mistake in our original declaration that the protocol was ‘easy’ to repeat,” the protocol continues. “This was our belief at the time, but it turned out to be incorrect.
Are you eager to try STAP 3.0 protocol?
3. Insurance for regenerative medicine products manufacturing in Japan
Japanese press reported about new law, which will enforce in insurance of errors in regenerative medicine products manufacturing. It will be effective in November.
Sompo Japan Nipponkoa Insurance Inc. plans as early as next month to sell regenerative medicine insurance products that would pay up to ¥500 million in benefits. Tokio Marine & Nichido Fire Insurance Co. and Mitsui Sumitomo Insurance are also planning to introduce similar products.
Introduction of such insurance as means of protecting patients from cell product manufacturing errors, will accelerate widespread adoption.
The wave of new companies, to which hospital will outsource cell manufacturing will rise soon:
Hospitals have thus far carried out both treatments and cell cultivation. The outsourcing, therefore, will likely enable regenerative treatments to be conducted more efficiently.
Also in November, the Health, Labor and Welfare Ministry will introduce a new system to give early approval for the sale of cultivated cells and other products for regenerative medicine.
4. Tools for scaling up mesenchymal stromal cells culture
Democratizing Cell Technologies blog has two great posts about scaling up of mesenchymal stem cells (MSC) production. In the first post, they overview new available tools for industrial MSC manufacturing – bioreactors and microcarriers:
PBS Biotech had a poster showing hMSC expansion in their vertical wheel bioreactors.
These high cell densities are a significant milestone for the field, as it is the first report (that I know of) of consistently greater than 1 million cells/mL over multiple runs, and with the potential to get to >3 million cells/mL.
The second post is about cost of goods and some other cell therapy-related talk from recent BioProcess Summit in Boston. On of amazing things they described from talk of company Janssen:
Like all good PD campaigns, they had quantified goals which were to 1) increase bioreactor yields by >50%, 2) increase downstream process recovery by >75%, and 3) decrease serum by 70%. All of this would dramatically increase the yield from every run and help reduce the CoGs of the overall process. Impressively, Dr. Kamaraju reported that they scaled up to 1000 L single use bioreactors and were able to consistently achieve yields of >300 Billion (3 e11!!!) cells per run.
I’d highly recommend both posts!
5. Targeting leukemic stem cell via glucose metabolism
Selective targeting of leukemic stem cell without damaging of normal hematopoietic stem cells has been a very difficult task. This week, David Scadden’s lab published a study, which demonstrates a possibility of such selective targeting:
This finding suggests that fine-tuning the level of glycolysis may be explored therapeutically for treating leukemia while preserving HSC function.
From the news coverage:
“Cancer cells are not like normal cells in a lot of ways, but one … is that they get locked into a particular way of behaving,” Scadden said. “These cells are so singular in the way they handle glucose that they create a unique opportunity to intervene. Normal cells don’t get so disrupted because they have other energy mechanisms in place.”
Private companies have been developing drugs that target cancer metabolism, but primarily in solid tumors. Scadden hopes that this study can open the door to industry partnerships and the generation of new treatments.
6. Ground-state pluripotency in human
Two recent studies described a new receipts for generation of so-called “naive” or “ground-state” human pluripotent stem cell. First, Rudolf Jaenisch lab proposed to use “kinase inhibitors that induces and maintains OCT4″. Second, Austin Smith’s team used short-term expression of two factors – NANOG and KLF2, to generate “ground-state” pluripotent cells.
7. Injectable niches for lowering therapeutic cell dose
You may have heard a lot about injectable hydrogels in regenerative medicine recently. One of the reasons to use hydrogels as cell carriers is lowering therapeutic cell dose. Recent study has demonstrated feasibility of such approach:
Dramatic improvement in cell retention, survival, and therapeutic effects enabled by the primed 3D microniches was demonstrated in treatment of critical limb ischemia (CLI) in mouse models compared with the free cell-based therapy. To the best of our knowledge, this is the first convincing demonstration of injectable and primed cell delivery strategy realizing superior therapeutic efficacy with the lowest cell dosage for treating CLI in mouse model.
8. New cell therapy blog
Please welcome in – CellTherapyWonk. This blog was just started by Mark McCall. Mark is an expert in “Cost of Goods” in cell therapy manufacturing. He recently got PhD from Center for Innovative Manufacturing in Regenerative Medicine of Loughborough University.