The COVID-19 pandemic is tearing through the country right as we are starting into the holiday season, but the wheels of science including cell biology keep going and we keep reading all the great work.
What news or papers caught your eye?
Here are some of the things I have on my list of reading. Also, check out our most-read topic here on The Niche of the last month or so in two posts here and here digging into what I see as Duke’s cord blood autism program entanglements with a for-profit stem cell clinic in Panama.
Mesoblast COVID-19 work gets a boost via Novartis
Novartis has signed a multi-$10 million deal with Mesoblast on MSCs for COVID-19. It’s a nice thumbs up from Novartis for the promise of the Mesoblast Remestemcel-L MSC product for ARDS including COVID-19 ARDS. If things go well, the deal could go into the high $100s of millions.
This is very encouraging news. You’d imagine that Novartis went through all the data and came out upbeat.
Now I’m curious about possible developments for Athersys, another big player here. They already had ARDS data before the pandemic. Also, a number of other firms like Cynata pursuing cellular therapies for COVID could be buoyed by the news of this deal.
For Remestemcel-L and the other cellular medicine products being tested for the novel coronavirus in the end it’ll all come down to the phase 3 data. I’m hoping it’s good news on one or more products, even though I have been somewhat skeptical of the rationales here vs. steroid use.
Recommended pubs
- AMD1 is required for the maintenance of leukemic stem cells and promotes chronic myeloid leukemic growth, Oncogene. AMD1 is quite an interesting enzyme.
- Adult Neural Stem Cells Are Alerted by Systemic Inflammation through TNF-α Receptor Signaling, Cell Stem Cell.
- PET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models, Science Advances. This approach sends the drug right to the tumor, which may be superior to systemic infusion where there are issues like crossing the blood-brain barrier. HDAC inhibitors such as panobinostat have sparked the development of resistance in DIPG cells, but cocktails of multipole drugs and radiation may overpower resistance and these combinations are likely going to be the best way to go with these high-grade childhood gliomas.
- Mechanical Tension Promotes Formation of Gastrulation-like Nodes and Patterns Mesoderm Specification in Human Embryonic Stem Cells, Developmental Cell and Cell Surface Mechanics Gate Embryonic Stem Cell Differentiation, Cell Stem Cell, both deal with cellular mechanics, which is a fascinating subfield of cell biology. See graphical abstract from the latter above.
- The Global Alliance for iPSC Therapies (GAiT), Stem Cell Research, Stephen Sullivan, et al. “The Global Alliance for iPSC Therapies (GAiT) is a new initiative to support the implementation and clinical application of therapies derived from pluripotent stem cells to the benefit of patients globally.”
Hi Paul,
You are correct that Athersys could be next to ink a deal. Its CEO has stated that they are in advanced discussions in the EU. However, they are NOT a “big MSC player”. They use proprietary multipotent adult progenitor cells. To refresh your memory, this is a unique cell type with substantially superior inherent scalability properties, where telomere lengths remain stable during proliferation to the extent that millions of doses can be obtained from a single donor. You can read about the MAPC/MSC differences here: https://www.frontiersin.org/articles/10.3389/fimmu.2019.01952/full It is interesting and encouraging for the adult stem cell sector that Novartis went ahead with the Mesoblast deal despite recent concerns expressed by the FDA on batch to batch consistency of Mesoblast’s MSCs, when the FDA chose not to approve Mesoblast’s therapy for pediatric GvHD and requested a new clinical study. I suppose Novartis believes it can overcome these concerns.
The other MSC player to watch is tiny Cynata Therapeutics in Australia. Their technology comes from work done at University of Wisconsin-Madison and can produce unlimited MSCs from a single donor by starting with donor iPSCs. MSC variation and scalability problem solved. I recently highlighted Cynata Cymerus technology in relation to the Mesoblast MSCs here: https://seekingalpha.com/article/4378377-mesoblast-needs-solution-to-msc-scalability-issues-cynata-therapeutics-answer The Novartis action also puts Cynata in a very favorble position.
Interesting developments.
WST
@WST, you are right and I corrected the reference to Athersys. I tend to think of the cells as similar. I also added a mention of Cynata.
I find it curious that MAPC are still so popular given that there was so much controversy surrounding the initial publications and the fact that even Catherine’s lab couldn’t reproduce the initial data. I spent time in Minnesota trying to learn the secrets of these cells and left empty handed after Jiang showed me a notebook full of notes in Chinese as my instructions and taught me nothing. Perhaps others have had more success.
@Brenton,
Thanks for giving us that peek into what happened. Can you say any more about how the MAPCs were supposed to be isolated and characterized?
I’d need to revisit the initial pubs to get the exact details, but essentially it was a bead based depletion of BM with GlyA/CD45 and then very low density plating of the remaining cells in media with PDGF, EGF and 2% FBS. Cells were subcultured at low confluence. Phenotyping was uninformative with standard MSC phenotype (I always found Mouse MSC to be highly positive for Sca-1 and Thy-1, whereas MAPC were supposedly dim for both), The standout feature was the ability of MAPC to contribute to multiple tissues both in blastocyst injections and post natal models. I tried this and failed too, but with MSC now MAPC given my inability to culture them (I’d come up with alternative protocols for isolating almost pure mouse MSC/committed progenitors/osteocytes from cortical bone and used these). Anyway, so the MAPC protocol was reasonably straightforward, but I’d been unable to get it to work and went to Mpls when in the US for a conference. Having learned nothing from the visit I went back home and tried for a while longer but got nowhere. Catherine ended up telling me they couldn’t reproduce their own data (Jiang and Reyes had done all the work) and attributed it to the magical powers of a specific lot of FBS that had ran out. There have been retractions (of Reyes initial paper describing the protocol) and amendments to others (errors in FACS data, falsified images in numerous pubs) and as far as I know nobody in Academia ever reproduced the results. Kudos to anyone that has got this working since then.