Stem Cell Program Aims to Cure Blinding Ailments

New CU research team collaborates to create CellSight



By Mark Couch  

(October 2018) Sight unseen, Mark Petrash, PhD, made the phone call to Valeria Canto-Soler, PhD.  

As director of research for the CU School of Medicine’s Department of Ophthalmology, his job duties include scouting talent and recruiting them to the Anschutz Medical Campus. With Naresh Mandava, MD, chair of ophthalmology, he had hatched a plan to launch an ocular stem cell research program.  

They had resources: a multimillion-dollar commitment from the philanthropic community, a campus with a new biomanufacturing facility and an established stem cell research program, and a database of 1,000 macular degeneration patients, so detailed that even the National Eye Institute wants to mine it.  

For Canto-Soler, the call from Petrash was like a dream coming true.  

“One day, totally out of the blue, I get a phone call from Mark Petrash, the director of research for this department,” she said. Petrash told her that he and Mandava had assembled pieces of a nascent program and invited her to visit.  

“They were now in the phase of looking for someone to build that program and to direct that program and they wanted to know if I would be interested in doing that,” Canto-Soler said.  

“CellSight was something I was dreaming about,” she said.  “Without a name. I was really dreaming about the possibility of creating a bigger program, a research program that would not include just my lab, but that would bring together different groups with different expertise.”  

Petrash had never met Canto-Soler, but her work had caught his and other leading ophthalmologists’attention.   

“I went out to experts in the field and Val Canto-Soler’s name kept coming up,” Petrash said. “She was at the Johns Hopkins Wilmer Eye Institute. We had never met, but I called her up. And she said, ‘Who is this?’”  

In 2014, Canto-Soler and her team figured out how to grow miniature human retinas in a Petri dish, starting from human stem cells.  

“I still remember the first time my postdoc came into my lab and said you need to come and see this,” Canto-Soler said. “When I actually saw that these mini retinas that we were developing have all of the cells and all that, I thought I was going to fall off my chair. I was sitting at the microscope and I just couldn’t believe it.”  

Collaborating with colleagues, they were able to determine that the mini retinas were responding to light. It was a breakthrough. The mini retinas had functioning photoreceptor cells capable of sensing light.  

“That was such an exciting moment,” Canto-Soler said. “That was a critical time for me. Starting from no experience, to being able to generate hundreds of mini retinas that respond to light and seeing that happening in my own lab, I started to believe that you can do almost anything, if you have the resources and the determination.”  

But you can’t do it alone. There is just too much for one investigator, one laboratory to make Canto-Soler’sdream come true. There’s science and art, business and balance, grants to write, patients to see.   

“Basically the idea was if you want to tackle something like restoring vision in blind patients, that’s something you cannot do with a small team and try to accomplish everything and understand everything,” Canto-Soler said. “The only way you can efficiently tackle that is bringing together a bigger team with expertise in complementary areas that know how to work together.”  

CellSight is the first step at building that bigger team, integrating four independent research groups to worktogether to find solutions to ocular diseases. Formed in 2017 on the Anschutz Medical Campus, CellSight has a custom-designed laboratory and four principal investigators working on independent, connected projects. 

The inspiration for CellSight dates to 2008 when Mandava had lunch with Dennis Roop, PhD, director of the Gates Center for Regenerative Medicine.  

“He and I had lunch way back then,” Mandava said. “I’m a retina specialist and I’ve always been interested in the potential for retinal cell transplantation. He’s a stem cell guru at the regenerative medicine center.”  

The Gates Center was established in 2006 by Diane Gates Wallach and John Gates in honor of their father Charles Gates to develop and promote stem cell therapies. While Charles Gates had been diagnosed with macular degeneration, the center was created to develop stem cell and regenerative medicine treatments for a variety of ailments.  

“I didn’t know this, but in the back of Diane’s mind, she had always wanted to proceed with an investment in macular degeneration,” Mandava said. “In 2014, Diane, Dennis and I talked about how she wanted to put together a $5 million matching investment. If we could raise $5 million, she would match it with $5 million for the $10 million we needed to launch a really strong stem cell initiative.  

“So we did it,” he said. “I think we were done in six to eight months.”  

The $5 million challenge grant from the Gates Frontier Fund inspired 19 additional donors, including a $2 million gift from the Solich Fund and a $1 million gift from Sue Anschutz-Rodgers. That funding, combined with an investment in the macular-degeneration patient registry by the late Frederic Hamilton, offered a sturdy base on which to build a program.  

CellSight aims to develop novel stem cell-based therapeutics to save and restore sight in patients with diseasescausing blindness, and Canto-Soler said CellSight will spare no effort to bring these therapies to the clinic as fast as possible.   

The most immediate goal is to address the need of therapy for patients affected by age-related macular degeneration, the leading cause of irreversible blindness in people over 50 years old. The team will start testing its new stem cell-based retinal transplant in preclinical animal studies within the next few months, with the hope of reaching clinical trials within the next four years.  

Canto-Soler went to work on assembling a founding team with state-of-the-art laboratory facilities.  

“The key to success for a program like Cellsight is that you have independent groups that are working together as a bigger team,” Canto-Soler said. “Each of them brings skills and insights in complementary areas of expertise, so the net effect is a great team able to move the science further and faster because of the collective effort.”  

Each lab in CellSight brings a unique perspective to the challenge.  

Canto-Soler is the director of the 3DRet Laboratory, which generates human mini retinas from human induced pluripotent stem (iPS) cells. The mini retinas, which take months to grow because they develop at the same pace as a developing human, are like a canvas for the others to explore.   

Natalia Vergara, PhD, a developmental biologist who, as a young scientist was fascinated by how newts are able to regrow retinas that are as functional as those it loses, leads the Ocular Development and Translational Technologies Laboratory.  

“She has developed a very innovative screening platform that you use for screening the effect of small molecules or other kind of drugs on retinal cells,” Canto-Soler said.   

Joseph Brzezinski, PhD, studies the genetic cascades that lead to particular types of cells.  

“We know how to make this retinal tissue,” Canto-Soler said. “We make a lot of rods, very few cones, so Joe brings in expertise in genetic manipulation. He has the expertise in understanding how to drive a stem cell to become a rod or a cone.”  

Omid Masihzadeh, PhD, builds better microscopes in the Laboratory of Advanced Ophthalmic Imaging.  

“He has very valuable expertise on noninvasive imaging technology,” Canto-Soler said. “That’s another very important gap in the field. Today, there are very limited noninvasive imaging techniques or tools in the clinic that you can use to diagnose and to follow the progression of retinal degeneration in a patient.”   

With a team assembled, the CellSight faculty also needed a great place to work.  

In addition to the Gates Biomanufacturing Facility, which opened in 2015 as the only site in an 800-mile radius meeting the high standards needed to produce cell therapies and biologics, the CellSight team also needed top labs.  

“When we were trying to recruit her here, I didn’t think we were going to build new facilities,” Brzezinski said. “I just thought we were going to make it work and she was like, ‘Yeah, I don’t think so. If I’m coming, we’re doing this the right way. We’re doing it up front. We’re going to make the investment and make it right.’ It was very smart of her to do that.”  

Because of the extreme sensitivity and the lengthy gestation of the mini retinas that Canto-Soler’s lab cultivates, she needed a space with strict environmental controls, including a training area and a quarantine chamber.  

With the support from donors and the University, the workspace was designed to meet exacting standards. 

“There is a moment that you realize that you are not alone, and that really empowers you” Canto-Soler said.“This is the huge challenge that we are trying to accomplish. You are basically facing one of the fourteeners and you know that you have to make it all the way up there for the first time, with no training, on your own.   

“And then you realize that you have a whole team backing you up, giving to you, coaching you, and making sure you have the resources that you need and that you are going to make it to the top. You get to the point where you say I just have to be part of this.” 

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