Ray Ramirez is the first patient in California to participate in a Phase III Clinical Trial of a new kind of dialysis shunt -- one that's made of human tissue. (David Gorn/KQED)
There’s new hope of a better and longer life for many patients with failing kidneys.
When someone’s kidneys stop working effectively to cleanse wastes from the blood, patients must have it done mechanically, using a dialysis machine to remove the blood, clean it, and send it back into the body. That process is hard on the veins because it requires such a large opening to do it.
Currently, patients get a plastic tube, or shunt, surgically inserted in a vein to hold it open for dialysis. But those shunts can get infected over time, or rejected by a patient’s immune system, and in any case, they need to be replaced about every year.
Now researchers are testing a new kind of shunt—one made out of human tissue. It combines with a patient’s stem cells to make the device part of the patient’s body; theoretically, it could last a lifetime.
‘I Just Accept It’
The first patient in California to participate in the Phase III clinical trial for the new shunt is dialysis patient Raymond Ramirez. (A Phase III clinical trial is the stage of research required before submitting a treatment for FDA approval.)
The 67-year-old resident of Whittier, Calif., just east of Los Angeles, says he’s a bit of a train wreck. He’s in a wheelchair because of an above-the-knee amputation on his right leg, and he stops rolling around his TV room for a minute to list some of his maladies.
“Omigod, it’s never-ending,” he says with a laugh. “In Vietnam, when I got wounded, they took out my ribs. So, on my left side, my ribs they’re just gone.” He has to think a minute for more.
“I’ve had intestinal problems, I’ve had bladder cancer, a tumor in my bladder,” he says, “I have a blind eye in my right eye. Blood clot in my retina."
Ramirez says he’s not one of those guys who likes to dwell on his problems.
“I’ve always been a happy guy,” he says. “I don’t like it, no, hell no, it hurts. I’ve hurt like crazy since I was a youngster. I just accept it.”
Right now, the big challenge for Ramirez is dialysis, because his veins are failing. And that's how he ended up in the Veterans Affairs Hospital in Long Beach on a recent day for an appointment with vascular surgeon Ian Gordon. Since the Phase III study is randomized, Ramirez has a 50-50 of getting the experimental human tissue shunt or the traditional plastic one.
How Does the Shunt Work?
Imagine one of those long foam noodles kids play with in the pool—hollow and kind of like cellulose—only it’s the diameter of your little finger. That’s what the shunts look like. But it’s an intricate process to get them to that stage.
First, you take human muscle cells from organ donors, and grow them into a tubular shape, says Jeff Lawson, chief medical officer at Humacyte, the North Carolina company that makes these things. As they grow, the cells secrete a sticky form of cellulose that holds them in the shape.
“So what’s left then is a scaffold of human tissue,” Lawson says. “We call it human extracellular matrix.”
Then you use a chemical wash to slough off the original donor cells, leaving the sticky cellulose structure behind—the foam noodle the diameter of your pinky finger.
The stem cell part of the equation, Lawson says, happens inside the patient.
“This scaffold, once implanted, uniquely becomes repopulated with their own stem cells," he says. "That then turns back into something that looks like a vascular cell. And it now transitions over the period of a few months into something that’s indistinguishable from your own tissue.”
If it works, applications of this technology are endless, says Dr. Gordon, from vein replacement to heart surgery.
“One of the holy grails, if you can use that phrase, in vascular surgery is to come up with a prosthetic artificial graft,” he says, “that has the same properties as the patient’s own blood vessels.”
So far, this one seems to do that.
A Voter Mandate to Get Results
This is the kind of success the state stem cell agency was aiming for, when California voters created it in 2004 by approving Proposition 71. The California Institute for Regenerative Medicine (CIRM), based in Oakland, now has just four years of funding left, and is putting more money into mature clinical trials.
While many people think of stem cell therapy as an a treatment that injects the cells into a patient’s body, there are other types of treatments that rely on stem cells.
“At CIRM we’re interested in anything that involves or uses stem cells in the correction of a disease process,” says CIRM CEO Randall Mills. “About a quarter of our portfolio product itself isn’t a stem cell.”
There are a couple of important reasons for CIRM’s move to fund more clinical studies, says UC-San Diego’s director of stem cell research, Larry Goldstein
“Ten years ago I don’t think there were that many projects that were really ready for clinical trials,” Goldstein said. “The field itself has developed projects that are at clinical stage.”
And, Goldstein says, the voters who created the agency wanted it to produce results.
“The voter mandate was more than just basic research," he says, "it was basic plus clinical.”
If the agency keeps pumping out these types of clinical results, Goldstein says, California voters may soon see another ballot measure to keep it going.
Humacyte officials say 118 patients around the world have received the new type of human tissue shunt – in both Phase II and Phase III of the clinical trial. About that many have participated in the trials and received the plastic shunt—neither the patient nor the doctor knows which shunt is to be installed until the moment in the surgery when a computer tells the doctor which one to use.
In the case of Ray Ramirez, he found out after he woke up from surgery, he got the plastic one.