W2W Part 2: Personalized Stem Cells

Posted by Sam Maddox in Research News on November 09, 2016 # Research

More from W2W 2016. Previously, we saw how Matthew Rodreick and his advocacy efforts got Minnesota to set aside $500,000 for SCI and TBI research. One project funded by the new money involves a type of stem cell that might push personalized medicine toward chronic SCI, combined perhaps with a novel scar removal strategy to encourage better nerve regeneration. The principal investigator is Ann Parr, a neurosurgeon/scientist at the University of Minnesota; she presented her work at the W2W meeting.

Before getting to the science, here’s some background on Parr. She began her clinical neurosurgical career at the University of Manitoba, then in 2003 moved to the University of Toronto to study stem cells in spinal cord injury in the laboratory of Dr. Charles Tator, the eminent doctor/scientist who began studying spinal cord injury almost 50 years ago, and at age 80, is as busy as ever. He’s well-known in Canada for his work with brain injury prevention and ice hockey; he has long been involved with the Reeve Foundation as an advisor and co-principal investigator for its North American Clinical Trials Network.

One other sidebar: The 15th Tator-Turnbull Symposium is set for November 18 in Toronto. This annual gathering of top SCI researchers is named for Dr. T and for Barbara Turnbull, the late Toronto Star journalist and advocate who lived with spinal cord injury. This year’s main lecture will be given by Claes Hultling, M.D., Ph.D., a neurobiology professor at the Karolinska Institute; Claes was himself spinal cord injured in 1984. One of the key organizers for the symposium is Michael Fehlings, the prominent neurosurgeon/researcher who trained with Tator in the 1980s, and who continues many collaborations with his mentor.

Back to W2W and Parr. One thing she learned at the Tator lab is that stem cells can be therapeutic for spinal cord trauma, but not all cells are effective. She’s worked with fetal cells, embryonic stem cells and various adult stem cells. Tator’s group has come to appreciate a cell called an oligodendrocyte progenitor, or OPC. It’s a stem cell that started out with no identity. It was nurtured toward being an oligodendrocyte, a nervous system support cell related to the formation of myelin. Myelin is the necessary lining on axons that allows chemical-electric signals to move up and down nerve fibers. SCI knocks out a lot of myelin, so this is a good cell to study.

You may recall that the first embryonic stem cell trial, the one from Geron now being carried forward by Asterias, uses an OPC, derived from a donated embryo source. Asterias has reported lately that the higher doses in the most recent patients are showing improvement beyond what would normally be expected in cervically injured people. Too early to tell what will come of those studies. Parr pointed out that OPCs from someone else – allografts, as in Geron/Asterias – come with two bits of baggage (ethical, e.g., embryo = person) and technical (OPC + rejection drug). Immunosuppression may come with side effects, she noted.

Parr and her team like OPCs but they have chosen to avoid the carry-ons. They plan to cultivate and transplant a patient’s own oligodendrocyte progenitor cells. No embryo, no drug. They start with a skin cell (fibroblast) and use little bioengineering trick to turn it into an OPC. This is called an induced pluripotent stem cell, iPSC.

Basically, iPSC rewinds the skin cell to a more primitive form, like an embryonic cell that has the potential to be any cell in the body. They then push the iPSC forward again toward becoming an oligodendrocyte. These programmed cells are reproducible, and as the label indicates, pluripotent. They behave almost exactly like embryonic cells, which makes this technology a landmark discovery, one that changed the course of the stem cell science; a Nobel Prize was given to cell pioneer Shinya Yamanaka for the work, published exactly 10 years ago.

Parr hopes to get a clinical trial going to transplant patient-derived OPCs. They have used human OPCs in animal models with success. What’s cool about her lab’s efforts lies in the production side. Up to now, working with pluripotent stem cells was unpredictable and relied too much on the experience of the operator. Now, the UM group has figured out how to eliminate variability; they are very close to having a cell manufacturing capability compliant with Good Manufacturing Practice (GMP), which would assure quality control, important for FDA commercial approval across clinical applications.

Parr said the lab has also figured out how to manufacture motor neurons.

One other issue that comes up with personalized iPSCs is that it takes 40 to 50 days to make a culture of OPC for a patient’s use. That has to be shortened for clinical utility and to hold back the cost of the process.

Now, regarding the spinal cord scar. It blocks the effect of cell transplants. Can it be removed? That would involve very difficult surgery inside the spinal cord, and of course the scar does not have distinct boundaries. Can it be degraded, as we have often heard with regard to chase, an enzyme that eats scar? That’s being studied, as we have reported, but issues remain regarding delivery of the enzyme that haven’t been worked out.

Parr suggested another way they’re going to try to ablate the scar: using a phototoxic drug called rose bengal. You squirt some rose bengal in the area of the scar, shine some light on it. It becomes like napalm, destroying everything it comes in contact with. Obviously this requires some exact placement and dosage.

Parr says there are reasons to consider this approach, citing the research of Eric Holmberg, now at the University of Alaska. He’s been using rose bengal in animal studies of spinal cord injury for a number of years, with some success, he reports. Holmberg is funded by the Spinal Cord Society (SCS), the nation’s first consumer-based research funding organization, started in 1978 by the late Chuck Carson, who lived north of Minneapolis in Fergus Falls. SCS hasn’t been in the news in a long time, so kudos to whoever is keeping Chuck’s Cure-Not-Care mantra going.

Next: the W2W buzz on spinal cord stimulation.

PS: all W2W sessions were taped. See @u2fpw2w for details.

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