“Regenerative medicine news under the microscope” is a new monthly feature highlighting big stories in stem cell research. I will sample the latest and greatest findings in recent press and package them into a single post.
This month was packed with interesting headlines. In this edition, I cover some big news from the team at CCRM, the arrival of “super livers” in Toronto, a newly-identified Neural G0 state, the latest on COVID-19 cell therapies, and more!
More ISSCR guideline controversy: Heritable genome edits
It wasn’t just their relaxation of the 14-day rule that’s raising eyebrows.
This month in Nature, decorated bioethicist Dr. Françoise Baylis is ringing the alarm bell. She’s drawing attention to another potential ethical issue with the revised stem cell research guidelines published by the International Society for Stem Cell Research (ISSCR) in May. The correspondence piece warns of a future where genome edits that are heritable may be permitted in the mainstream.
Read about the inconsistencies she picked up on here.
The “super liver”
You might not expect me to start an item about a “super liver” by telling you about the pancreas, but that’s what’s about to happen.
Our pancreas, which is just behind the stomach, produces critical enzymes that aid in digestion, plus hormones for sugar processing, aka insulin. A condition called pancreatitis will strike some of us, resulting in pathological inflammation of the organ. It can present and resolve quickly, or it can become a chronic condition, causing cellular damage, reduced pancreatic function, and severe pain. Some cases can even be life-threatening. In extreme cases the pancreas may be completely removed, relieving the patient of pain; however, this will render the patient diabetic and in need of insulin from external sources. If a patient doesn’t want to go down this route, they may end up on heavy narcotics to manage the pain.
Enter a relatively new treatment: total pancreatectomy and islet autotransplantation. This involves the complete removal of the pancreas followed by extraction of the insulin-producing cells from the inflamed organ, and injection of these cells into the liver. There, they will take root and thrive. This regenerative medicine solution both relieves the painful condition and satisfies the patient’s need for insulin using their own cells.
This month, CTV reported on one of the first two patients to undergo this procedure at Toronto General Hospital. Seeing as the incidence of pancreatitis seems to be increasing worldwide for unknown reasons, this treatment option is an invaluable asset to our city. By the way, the islet cells were isolated, purified and concentrated at CCRM’s Centre for Cell and Vector Production, a Good Manufacturing Practices-compliant facility. The cells were then returned to the hospital to be implanted into the patient’s liver.
CCRM signs new alliance agreements to advance regenerative medicine in Canada and abroad
This story broke on May 31st, so it just escaped last month’s blog.
As you may know, CCRM provides a trifecta of financial, business and scientific support to institutions looking to commercialize regenerative medicine inventions.
The list of new partners in CCRM’s announcement is star-studded, and includes major leaders in the field:
CANADA:
- McGill University
- McMaster University
- University of Calgary
- Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital
AUSTRALIA
- Monash University
NETHERLANDS
- Starfish Innovations, a subsidiary of Leiden University Medical Center
This is good news for CCRM and the field. I’m very much looking forward to following these partnerships and can’t wait to hear about the work that’s accomplished.
Lulling brain cancer to sleep: Neural G0
The cell cycle is one of the first things we learn in elementary biology, and yet we’re still digging up new cell states with each passing year.
After conducting scRNA-seq on expanding human neural stem cells, O’Connor et al. identified a quiescent-like state called Neural G0 in cell types derived from neuroepithelial-type cells. Specifically, this state was present during both mammalian neurogenesis and, critically, in gliomas. What’s more is that gliomas with cell populations and gene expression associated with the Neural G0 state were less aggressive and were associated with extended patient survival. The authors go on to identify specific molecular modulators associated with release from the Neural G0 state through knockout experiments.
Why is this great news? While current cancer treatments largely work by killing cancer cells, this process can release cellular debris into the microenvironment that may potentially render remaining cancer cells resistant to the drug.
This study opens up the possibility of putting the cancer to sleep. A specific example offered by the researchers was the administration of a Neural G0-inducing drug following a tumour resection to prevent relapse. Now it’s just a matter of identifying a druggable gene target that would be able to do this, specifically by determining which genes keep the cells in quiescence (as opposed to the genes which they’ve already identified, which release the cells from quiescence).
A pro-take on stem cell therapies and COVID-19
If you’re reading this blog, odds are you’re familiar with Dr. Paul Knoepfler. He wrote an in-depth, highly insightful piece for STAT this month on the realities of stem cell-based COVID-19 treatments. Here’s a quote that really sets the tone:
“The sobering reality is that the FDA has approved relatively few cell and gene therapies, and only a tiny subset of these use bona fide stem cells. Yet the more harmful or lethal the disease, the greater the odds that ‘stem cells’ are being pitched to fix it. It’s an equation for false hope and other problems like wasted research dollars.”
Dr. Knoepfler also co-authored a study published this month in Regenerative Medicine with his student at UC Davis, Mina Kim, comprehensively analyzing approved clinical trials involving cell therapies for COVID-19 to try and predict their impact and ascertain their rigor. Interestingly, they predicted low potential for quick, concrete impact, but found that these clinical trials may be more rigorous than non-COVID clinical trials.
An in vitro lung model: COVID-19 and beyond
I think most of us would agree that science has risen to meet the challenge of the pandemic, time and time again. In previous blogs, I’ve highlighted in vitro systems currently being used to study the virus, a collection which grew this month to include a model of airway epithelial cells.
The authors use an induced pluripotent stem cell-based protocol which they say simplifies the process by which human upper airways can be manufactured for model systems. They achieved the differentiation of a pseudostratified epithelium containing pertinent cell types of the upper airway and, as would be expected, they observed the production of both mucus and functional cilia.
The next step was, of course, to try and introduce SARS-CoV-2 into the system. They were able to do so successfully, demonstrating both infection and replication. This places their model in a strong position to be of service in the pursuit of therapies for respiratory infections, in addition to drug toxicity screens.
Eyes on dangerous and unproven stem cell therapies: Growing concerns
This month, concerns were voiced from multiple sectors calling out stem cell clinics administering “treatments” directly to consumers, based on little to no scientific or clinical evidence, often resulting in injury or death.
In this paper, the authors call on the World Health Organization to establish an Expert Advisory Committee on Regenerative Medicine, both to confront the issue and to provide guidance.
An article by Pew appealed to the American Food and Drug Administration specifically, citing the magnitude of the problem in the United States. Shockingly, over 700 clinics there offer “stem cell regenerative medicine interventions” that are unproven and thus dangerous to the public.
Resolving “chemobrain” using stem cell-derived exosomes
Chemobrain is a type of cognitive impairment experienced by some cancer patients following certain treatments, including but not limited to chemotherapeutic agents such as doxorubicin (dox). Symptoms can vary: decreased short-term memory, difficulty finding words, attention and concentration issues, and a reduced ability to multi-task may be experienced. As one might imagine, this condition causes considerable distress in patients, as it can last for months to years following treatment cessation.
Dox, specifically, has been found to induce some degree of neurodegeneration in the brain. The study in question, which was a joint exploration by Ain Shams University in Cairo and the American University of Beirut, had a look at exosomes derived from bone marrow mesenchymal stem cells (MSCs) to see if these could be used to improve chemobrain in rat models of dox treatments. Why this cell type, specifically? MSCs have been found to promote brain repair in other neurodegenerative conditions, including Alzheimer’s, Parkinson’s, and even following strokes. MSCs, which themselves do not activate strong immune responses when administered, secrete pro-repair molecular components in exosomes (extracellular vesicles). This made MSCs an attractive cell type to explore further.
The authors found that following administration of the exosomes (specifically containing repair-promoting micro-RNA payloads, amongst other healing factors), cognitive and behavioural deficits associated with chemobrain in rats were successfully eliminated.
Although the researchers suggest that more work will be required before moving this treatment to the clinic, this is a promising step in the field’s efforts to improve cancer patients’ quality of life.
Additional recommendations
Here are some papers/headlines that I didn’t have room for above:
Cells or drugs? The race to regenerate the heart. Benjamin Plackett in Nature.
Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brain – implications for brain plasticity and repair. Delgado et al. in Science.
Adipose-derived stem cells protect motor neurons and reduce glial activation in both in vitro and in vivo models of ALS. Ciervo et al. in Molecular Therapy – Methods & Clinical Development.
Cedars-Sinai Medical Center awarded $12 million for ALS clinical trial. Howard Fine, Los Angeles Business Journal.
FDA approves StrataGraft, a regenerative medicine solution, for the treatment of adults with thermal burns. FDA News Release.
Pride month TikTok drive encourages stem cell donations from gay, bi men. Jeremiah Rodriguez for CTV News.
State of the art review on regenerative medicine for neurological diseases. Terry C Burns in The British Medical Journal.
Development of next-generation tumor-homing induced neural stem cells to enhance treatment of metastatic cancers. Jiang et al. in Science Advances.
Metabolically engineered stem cell-derived exosomes to regulate macrophage heterogeneity n rheumatoid arthritis. You et al. in Science Advances.
In vitro characterization of human bone marrow mesenchymal stem cell-derived motor neurons induced by epigenetic modifiers. Sanooghi et al. in Egyptian Journal of Medical Human Genetics.
Stay tuned for my next post, coming up in July!
Lyla El-Fayomi
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