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The Cure to Cancer, Blindness, and Stroke

Dr. Molly Shoichet is all about attacking old problems with new solutions — and she’s on the verge of revolutionizing the way medicine treats illness, disease, and injury.

What can regenerative medicine do for you?

I’ll start with some context for what it could do for me.

After enduring a near-catastrophic aortic dissection, it was discovered that my mother-in-law had recently suffered a series of mini-strokes that predated her recent emergency.

This was just over two weeks ago, and though her progress since this major trauma has been encouraging, she faces a long journey of rehabilitation.

My father-in-law has been blind since his late youth, and he’s long since resigned to never seeing the faces of his wife, children, grandchildren, or great-grandchildren.

One of the great anxieties growing from my mother-in-law’s hospitalization is that she, my father-in-law’s eyes, may no longer be able to translate the world for him.

My mother died of ovarian cancer a decade and a half ago, at just 53. My older daughter enjoys flashes of sweet memories with her grandmother, but her younger sister must rely on photos.

She only had a few years to do it, but being a grandmother was the role of a lifetime for my mother.

Stroke. Blindness. Cancer.

These are a few of the things regenerative medicine can solve.

In an hourlong presentation for the Perimeter Institute for Theoretical Physics’ Public Lecture Series, Dr. Molly Shoichet, who holds the Tier 1 Canada Research Chair in Tissue Engineering at the University of Toronto, explains how her team is changing the way we look at treating cancer, blindness, and stroke.

Members of Shoichet’s team have been able — using these biomimetic hydrogels — to better understand the role of extracellular migration in metastasis.

“It turns out that most of what we know about the cells in our body is based on growing cells in hard plastic dishes… petri dishes,” Shoichet said. “But we don’t have any hard plastic in us. And we’re 3-D. Our cells are not growing on a flat surface.”

Cells taken via humans via biopsies do not grow well in petri dishes.

Shoichet’s team wanted to find a way to replicate in the laboratory the way cells actually grow in human bodies. That meant soft material in a 3-D environment.

Creating such an environment would allow researchers to test the efficacy of drugs and therapies in a lab before administering them to human patients.

Among the materials tested were hydrogels, or materials swollen with water, such as Jell-O. But Shoichet insists, “We’re not using Jell-O.”

She turned to hyaluronan, or hyaluronic acid, a material that’s present “natively” within the cancer tissue. Hyaluronan is used by doctors to smooth our wrinkles, and it’s also used to treat osteoarthritis.

“It mimics the environment in which cancer cells grow in our bodies.” But researchers couldn’t simply put it in the refrigerator to create a hydrogel.

Shoichet’s innovation was to introduce polyethylene glycol to hyaluronan to create a “biomimetic hydrogel” that would allow researchers to control its mechanical, chemical, and architectural properties and grow laboratory cells in an environment much like the human body.

It took about a decade to find the right balance.

Members of Shoichet’s team have been able — using these biomimetic hydrogels — to better understand the role of extracellular migration in metastasis.

“We have great control in creating an environment that mimics the way cells grow natively.”

And now her team is ready to start taking cancer cells from patients and drug-screening them.

Shoichet’s biomimetic hydrogel system will also facilitate personalized medicine, where laboratory environments are built specifically around a particular individual’s cells.

The strategy of regenerative medicine in this context is to “stop the disease and actually reverse it.” The ultimate goal is to restore a patient’s vision after they’ve lost it.

Right now regenerative medicine research is focused on “cell transplantation,” a strategy based on replacing actual cells that are lost after a major injury or as the result of a serious disease.

That means injecting cells into the back of the eye (or the retina) for cases of blindness, into the brain for cases of cancer, or the spinal cord for injuries that disrupt signals between brain and body.

The cause of most blindness is retina degeneration, whether due to age (macular degeneration), hereditary disease (retinitis pigmentosa), or other conditions (diabetic retinopathy).

Current treatments only slow the progression of these causes. But progress they will, even with these drugs.

The strategy of regenerative medicine in this context is to “stop the disease and actually reverse it.” The ultimate goal is to restore a patient’s vision after they’ve lost it.

Targeting the retina’s seven layers of cells is a complicated process.

But we have a very good idea of where to focus with regard to the three major causes of blindness. Photoreceptor cells and retinal pigment epithelium cells, at the back of the eye, are the ones that die. Those are the ones to replace.

Good news: One of Shoichet’s collaborators, Derek van der Kooy, “discovered that we all have retinal stem cells in our bodies.”

As Shoichet explains, “A stem cell has the capacity to become itself, and it has the capacity to become all other cell types in that tissue.”

The critical factors here are transplanting cells “right where they’re lost” and “in an environment that will promote their survival and integration.”

The nervous system, as Shoichet explains by analogy, is much like an electrical cable. If you sever it, you have to take care to put it back together in a way that will allow signal conductivity.

You can’t just throw a bunch of wires — or a bunch of cells — at the problem.

The hydrogel Shoichet’s team invented facilitates the survival of injected cells.

The introduction of a separate molecule — alpha aminoadipic acid — before cell transplantation would help the new cells integrate with existing, functioning cells.

So there’s success from a tissue perspective, though, as Shoichet concedes, “We’re not sure what’s actually happening here.”

“This is the great thing about science,” notes Shoichet. “You get a great result, and then you go, ‘Wait, maybe we should re-examine that.”

The outstanding question is whether the cells are actually integrating or just transferring genetic information to the existing structure.

More good news: Laboratory mice have shown “functional recovery of pupillary light response” following cell replacement.

The survival and integration of more cells are the present goals for Shoichet’s team.

And neural stem cells are able to become any and all the cells in our brains. That means your brain can repair itself.

As Shoichet explains, “When I went to high school, I learned that we were born with a certain number of nerve cells in our brains. Some of you may have learned that as well.”

But in the 1990s, Brent Reynolds and Sam Weiss discovered that “we actually have stem cells in our brains.”

And neural stem cells are able to become any and all types of cells in our brains. This indicates that the brain can repair itself.

It’s also the case that when a person suffers a stroke, their neural stem cells are stimulated, “but not enough to promote functional repair.”

We’ve seen more than 1,000 failed clinical trials for therapies designed to treat damage suffered by victims of stroke. So the task may seem Sisyphean.

But Shoichet’s guiding principle is to come up with “very different” strategies to promote repair.

“The holy grail of regenerative medicine is trying to get those stem cells that are already resident in us to regenerate that lost tissue.” And that’s her team’s focus.

Based on laboratory research into the use of an invasive catheter-and-pump system designed to promote repair and recovery, Shoichet’s team hypothesizes a Band-Aid-like mechanism applied directly to the brain that would deliver therapeutic hydrogel to stimulate regenerative stem cell growth.

Why not just a pill or intravenous delivery?

Well, the short answer is that Shoichet’s solution overcomes the blood-brain barrier where simpler deliveries simply cannot — by going around it.

Regenerative medicine addresses the root causes of diseases, injuries, and congenital conditions.

Right now, in many medical situations, managing symptoms is not the best but the only treatment available to doctors.

But researchers like Shoichet are finding new ways to solve age-old problems.

Old Things New

Anyone who’s ever worked sales leads over the phone can appreciate David Mamet’s Glengarry Glen Ross, an extraordinary play that explores the brutal competition of the human race.

The film is very nearly the stage version’s equal. And it includes a monologue that doesn’t appear in the source material.

As Kevin Lincoln details for Vulture, “Alec Baldwin’s Role in the Movie Glengarry Glen Ross Was a Repaid Favor.” How Baldwin ended up in Mamet’s movie is a funny story of genius springing from the banal.

It doesn’t take “brass balls” to make it through the ad in the video featured in the link above. “Have I got your attention now?”

Because the 90-seconed mini-feature on the provenance of “F%#k you!” (how he identifies himself) and/or “Blake” (how the credits identify him) is time well spent this weekend.

While you’re at it, watch the movie (it’s now available on the Starz network) and witness Alec Baldwin, in only seven minutes of screen time, steal a picture also featuring Jack Lemmon, Al Pacino, Ed Harris, and Kevin Spacey.

“A… B… C. A, ‘always,’ B, ‘be,’ C, ‘closing.’ Always be closing…”

Smart Investing,

David Dittman
Editorial Director, Wall Street Daily

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