√ Stem Cell Good News: Spinal Cord Injury Trial, Cirm, Grants, More

Cropped Image of Jan Nolta from SacBee

Stem cell good news time…and more will be coming later this week.

The stem cell and regenerative medicine world sometimes feels chaotic because so much is going on both on the positive and negative sides of things. There is a whirlwind of activity and developments, and a tendency sometimes within our arena to just avoid bad or complicated news. One mission of this blog is to try to cover the full spectrum of developments including difficult situations, but I also want to focus in on a regular basis on what I see as good news. Below are some recent upbeat developments.

Asterias. The company announced encouraging one-year data from a small cohort of spinal cord injury patients in their clinical trial that definitely constitutes stem cell good news. Not only is their AST-OPC1 product showing a strong safety profile, but also there are continuing signs of potential indicators of efficacy including functional recovery beyond expectations of what would be seen by spontaneous recovery alone in 4 out of 6 patients. It’s still early days and this is an open label, uncontrolled study, but at this point this is very good news so far. See my interview with Asterias leadership from 10 months ago. Note that the clinical work of the company is supported in part by CIRM.

CIRM leadership. Our California stem cell agency has a new President and CEO in Maria Millan, who has been a leader at CIRM for quite some time. This is a positive step for CIRM in charting its future course. Millan replaces previous CEO Randy Mills and has been interim CEO since Mills left. Here’s more on this development from CIRM.

CIRM Grants including to UC Davis. CIRM recently has given out some important new funding including a large award to UC Davis to our Stem Cell Program to develop an Alpha Clinic here under the leadership of Jan Nolta. More from the SacBee (with picture from them of Jan above) on this. Way to go, Jan and the team!

Retina in a Dish Award. The NEI awarded a Retina Organoid challenge grant to Erin Lavik of the University of Maryland. As to the project, NEI said, “Lavik’s team proposed building a retina by screen printing 4dukt neural progenitor-derived retinal neurons in layers that mimic the structure of the human retina. The system is designed to be scalable, efficient, and reproducible, enabling high-throughput screening for drug testing.”

ViaCyte. This San Diego-area stem cell biotech also received a CIRM grant to support its work on stem cell-based therapies for diabetes, in this case specifically for high-risk Type I diabetes. I believe this privately owned company is one of the more promising regenerative medicine biotechs out there. See my past posts on ViaCyte here.

On a more individual level, my colleague Veronica Martinez-Cerdeno and I were excited that we got the cover image (above) for the latest edition of Stem Cells & Development with our recent xenotransplant hIPSC and hESC paper (more on the paper here).

What’s your stem cell good news, whether it is your own and something upbeat elsewhere in the stem cell field?

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√ Australia Takes Big Step To Curtail Dangerous Stem Cell Clinics

The ability of for-profit stem cell clinics to pitch unproven, risky stem cell offerings to patients may soon get much tougher in Australia.

The country’s Therapeutic Goods Administration (TGA), which has some similar responsibilities there as the FDA does here in the U.S., announced planned new reforms that’ll put stem cell clinics under more scrutiny and more thorough oversight. Hopefully it’ll in many ways provide patients with more protections.

While details remain to be determined, there are four major components to the TGA policy change, which should be implemented in early 2018:

1. “Not permit direct advertising to consumers of autologous cell and tissue products, similar to the prohibition in Australia in the advertising of prescription medicines, but noting that services (that do not mention specific products) will still be permitted to be advertised.


2. Exclude from regulation by the TGA only those autologous cell and tissue products that are manufactured and used in a hospital by a medical or dental practitioner, for a patient in the care of the same practitioner.


3. Introduce regulation by the TGA, with exemptions from some requirements, for autologous cell and tissue products that are:
   
   
   
   • minimally manipulated, and
   
   
   • for homologous use only, and
   
   
   • manufactured and used outside a hospital by a medical or dental practitioner,
   
   
   • for a patient in the same practitioner’s care.
   
   
   
   


4. Regulate under the Biologicals Regulatory Framework those autologous human cell and tissue products that are:
   
   
   
   • manufactured and used outside an accredited hospital, and
   
   
   • more than minimally manipulated, or
   
   
   • for non-homologous use.”
   
   
   
   

In a helpful piece Professors Megan Munsie, Cameron Steward, and Ian Kerridge, detail this legal development, which is largely viewed as good news. Early in their piece, Munsie (who is also Deputy Director of the Centre for Stem Cell Systems and Head of Education, Ethics, Law & Community Awareness Unit, Stem Cells Australia, at University of Melbourne) and colleagues outline the potential impact:

“Regulation of stem cell treatments being offered outside hospitals will be increased. It will acknowledge the risks of these treatments, and advertising of certain treatments will be prohibited.

While more specific details are not yet available, it seems at last possible the most egregious practices of suburban stem cell clinics will be severely curtailed.”

With more than 60 stem cell clinics now, Australia has a growing masalah in this area much like the U.S. and other countries where such clinics are mushrooming. Hopefully this new policy will have strong, positive impact in Australia. It’s unclear why dentists should be added into the mix of stem cell providers, although here in the US there are rumblings about other practitioners besides physicians more often getting into selling stem cells including chiropractors and less often dentists. Also, hopefully hospitals will not jump into offering unproven stem cells in Australia as apparently they’d be exempt from the new policy’s oversight.

In the U.S. the situation is mixed as the FDA under new Commissioner Scott Gottlieb has taken some strong, if preliminary action and California has a new state law mandating that clinics put up postings and inform patients about what they are getting into, but Texas has a new state law that, while not nearly as risky as it could have been prior to last-minute legislative changes, still is decidedly pro-clinic in some ways. A push for a national right-to-try law in the U.S. may also make things more complicated on the stem cell front.

Munsie and her coauthors see the new TGA policy as a positive step but more details are still needed and vigilance is required in this arena:

“The dangers here are clear. While regulatory reform is welcome, they will remain ineffective unless the TGA and other regulatory bodies have the will, power and resources to enforce them. And unless this happens – patients will continue to be harmed.

Selling stem cells has been a big business in Australia for too long. After two public consultations and much deliberation, we have some action. Researchers, health practitioners, patients and regulators have an interest in making sure the proposed changes to the regulations work.”

With potential positive steps such as the California law, the newly emboldened FDA, and this development with the TGA in Australia, much of the simpulan outcome will depend on practical issues and enforcement on the ground of stem cell clinics. Actions need to back up the words from governmental agencies. In each case, there also remain potential loopholes through which stem cell clinics can try to operate and continue to siphon money from vulnerable patients even as they put these folks at risk by experimenting on them without governmental permission.

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√ Stem Cell Good News For The Holidays: Biotechs, Fda, Organoids

I can see many reasons to be jolly on the regenerative medicine front as we get deeper into the holiday season as there is quite a lot of stem cell good news even if there is also some not so good news.

In today’s post the focus is on the good news of late.

Atsuhiro Taguchi and Ryuichi Nishinakamura, part of Figure 4, Cell Stem Cell 2017, kidney organoids in development.

Semma Therapeutics, a stem cell diabetes biotech, raised more than $110 million. I’m eager to see how the next few years play out with the healthy competition between them, ViaCyte, & others in this area. The end result of this good news now will hopefully be at least one safe, effective new diabetes treatment in the future within less than a decade. You can read my recent interview with ViaCyte leadership here.

More on the biotech front, as Amgen invests big bucks into direct reprogramming firm Fortuna, which focuses in part on the development of autologous neural stem cells for a variety of conditions.

The promise of cell-gene therapy combos is exemplified by the recent effort that restored basically the entire epidermis of a young boy with epidermolysis bullosa, who would have otherwise died. You can read about my take on the Nature paper reporting this finding here. It’s one study, but I see it as good news. You have to start somewhere with a new, transformative approach.

Recent FDA actions and words on stem cells are good news on a number of levels in terms of clarity and strength, which I will optimistically say are likely only the beginning of a different phase in our field. See more of my thoughts and information on this here. I believe that new Commissioner Scott Gottlieb is serious about differentiating between good citizens in this arena, whose path we should facilitate, and those on the other end of the spectrum who are after patient’s money and willing to risk their customers’ health and even lives. You can see text of Gottlieb’s broader testimony last week before Congress on 21st Century Cures here.

There are unfortunately usually too many steps from discoveries to the bedside to help patients, but each step is something to be happy about as long as we have a balanced view and don’t succumb to hype. New work on the organoid front suggests the idea of “kidneys in a dish” is a step closer to a future reality. The scope of kidney disease is so profound that more effort is needed in this area. You can see the beautiful data above (part of Figure 4 from their Cell Stem Cell paper) from the work by Atsuhiro Taguchi and Ryuichi Nishinakamura mentioned in the overview article.

What’s your stem cell good news for the holidays?

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√ Stem Cell Good News: Novel Cancer Work, New Ca Bills, Alzheimer’S, More Pubs

Graphical abstract of van der Kant, et al. Cell Stem Cell 2019. Article mentioned at the bottom of this blog post.

There’s nothing like stem cell good news and interesting publications to perk one up on a Monday. Enjoy.

What recent papers have struck you as exciting?

Novel stem cell-based cancer approaches (Part 1)

It was exciting when Fate Therapeutics got the first induced pluripotent stem cell (IPSC) IND in the U.S. for their IPSC-derived natural killer cell (NK) product. Now in another milestone the first patient has received the investigational NK therapy at UC San Diego. From UCSD, “After 10 years in remission, Derek Ruff’s cancer returned, this time as stage IV colon cancer. Despite aggressive rounds of chemotherapy, palliative radiotherapy and immunotherapy, his disease progressed. In February 2019, as part of a phase I clinical trial at Moores Cancer Center at UC San Diego Health, Ruff became the first patient in the world to be treated for cancer with a human-induced pluripotent stem cell (iPSC)-derived cell therapy called FT500.” This is very good news!

Novel stem cell-based cancer approach (Part 2)

On another IPSC front, a big biotech development also is encouraging on the cancer fight. From the PR, “Leaps by Bayer, the investment arm of the global life sciences company Bayer, and Khloris Biosciences, a biotechnology company, announced today that they have joined forces to develop novel, first-in-class anti-cancer vaccines based on human induced pluripotent stem cells (iPSCs). This technology has the potential to address one of today’s biggest issues in human health: to prevent and cure cancer.”

A tale of two new positive California stem cell bills.

Our state passed Roman Reed Spinal Cord Injury Research Act of 1999, which pioneered stem cell research for spinal cord injury. A new bill, AB214, would give this unique research jadwal $5 million in additional funding. I predict it will pass. Roman is one of the top stem cell advocates in the world and was the first recipient of The Niche’s Stem Cell Person of the Year Award.

California is a leader in a stem cell research in the U.S. and the world, but it is also leading the way on stem cell-related legislation. We were the first state to pass a law aiming to help patients better understand what they are getting into with stem cell clinics. Now a new bill, AB617, would more rigorously oversee stem cell clinics in our state. Hopefully, this legislation will become law and California can continue to lead the way amongst states trying to deal with stem cell clinics.

Some notable pubs and news:

Cool exosome one led by Johnathon Anderson from right here at UC Davis by some friends and colleagues. Primed mesenchymal stem cells package exosomes with metabolites associated with immunomodulation.

IPSC modeling Alzheimer’s. Inhibiting the accumulation of cholesterol in iPSC-derived neurons prevents the accumulation of both β-amyloid and tau. See the original Cell Stem Cell article here from Larry Goldstein’s lab at UCSD and graphical abstract image above from that van der Kant, et al. paper.

Towards universal stem cells. Targeted Disruption of HLA Genes via CRISPR-Cas9 Generates iPSCs with Enhanced Immune Compatibility. See also this recent relevant post on other efforts in this area.

Japan Significantly Relaxes Its Human-Animal Chimeric Embryo Research Regulations

Concise Review: Human‐Animal Neurological Chimeras: Humanized Animals or Human Cells in an Animal?

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√ Stem Cell Good News Pubs In Late May 2019

The exciting and sometimes downright crazy giant stem cell ecosystem of legit research and unproven stem cell clinics could use a dose of good news now and then. In today post, I highlight some upbeat news and some interesting recent pubs.

Enjoy!

Sangeetha Vadakke-Madathil, et al. screenshot of video, PNAS 2019.

From a team led by Hina Chaudhry, MD, Director of Cardiovascular Regenerative Medicine at the Icahn School of Medicine at Mt. Sinai, a new PNAS pub, “Multipotent fetal-derived Cdx2 cells from placenta regenerate the heart.” Congrats to first author Sangeetha Vadakke-MadathilThis is a mouse study, but it has some translational potential for human patients. It also includes cool videos (you can see a screenshot of one at right.)

I need to read the paper before I can say how fully convinced I am of the central idea, but it’s on my reading list. For instance, I saw that in one figure they say they ruled out cell fusion in at least one context, but fusion is always a potential complicating factor with stem cell transplantation studies. For instance, in a hESC and hIPSC transplantation study my lab did with our colleague Veronica Martinez-Cerdeno, we found extension fusion of these stem cells with mouse brain cells. Again I need to dig into the pub in the coming week or two. Looks cool.

Single-cell proteomics! Wow from Cell Stem Cell. Single-Cell Proteomics Reveal that Quantitative Changes in Co-expressed Lineage-Specific Transcription Factors Determine Cell Fate.

Highly Efficient and Marker-free Genome Editing of Human Pluripotent Stem Cells by CRISPR-Cas9 RNP and AAV6 Donor-Mediated Homologous Recombination. Another Cell Stem Cell piece, this one from a Matthew Porteus-led team.

Pluripotency or differentiation? That is the question. Here’s the original Molecular Cell paper from a team led by Micha Drukker, which has some insights into paraspeckles. You can learn more about paraspeckles here. In part, this paper (Modic, et al.), shows that NEAT1_2 Recruits TDP-43 into Paraspeckles. Congrats to first author Miha Modic.

Stem cell differences could explain why women are more likely to develop adrenal cancer.

New Progress in Stem-Cell-Free Regenerative Medicine

Highly Purified Extracellular Vesicles Derived From Induced Pluripotent Stem Cells

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