BONE FRACTURE vs. THE CALIFORNIA STEM CELL PROGRAM: Disease-a-week Challenge #7
By Don C. Reed
In 1978, my brother David Reed was driving his motorcycle up a winding mountain road near Santa Cruz, California, when a truck came around the other side.
”I smashed into him head-on at 60 mph, flipped over the truck and rolled down a cliff,” he said.
David landed in a tree on the hillside, with his motorcycle on top of him, shattering his right leg. Fortunately, the truck driver was a decent sort, and did not leave. He called for help, and a stretcher rescue was carried out.
Bone protruded through the fabric of David’s jeans in two places. His tibia, femur and fibula were all horrifically fractured.
Should David’s leg be amputated? I tried to persuade him to keep it, because, “What if they found a way to cure it later on?”.
I had no idea what I was asking him to endure.
The pieces of broken bone had to be removed, cored out, stacked on metal rods, and put back in. After this “healed”, the rods had to be removed, and bone grafts from his hip put in. An experimental device called an osteo-stimulator was used to try and increase bone growth.
His calf had titanium spikes sticking out both sides, like the snout of a sawfish.
David wore shorts a lot during the months of convalescence, and honesty compels me to report that was one ugly leg. The smell was pretty powerful too. If he went to a movie and set his bare leg up on the seat in front of him, he could clear the area. People would sniff the air, take one quick look, and relocate.
When it seemed the worst was over, David completed nursing school, and worked years in that profession.
But then he fell on concrete and broke his leg again, terribly, so that part of the metal rod protruded: more surgery, more bone transplanted from his hip.
After 12 operations and much loss of bone, my brother’s right leg was three inches shorter than the other. He wears a built-up shoe on that side, for balance.
He says he is glad he kept the leg, because he can walk, so long as no one is in too big of a hurry. But the pain continues, and he is permanently disabled.
There has to be a better way: to heal complicated bone fractures quickly, completely, and with a minimum of pain.
At the Cedars-Sinai Medical Center in Southern California, stem cell scientist Dan Gazit and orthopedic surgeon Hyun Bae are trying to do just that.
Dr. Bae graduated from Yale with honors, and is a board-certified orthopedic surgeon at the Los Angeles Spine Institute; https://www.laspineinstitute.com/DrBae.htm
Dr. Gazit heads a research lab at the Department of Surgery and Board of Governors Regenerative Medicine Institute of Cedars-Sinai.
Listen to how Dr. Gazit describes the target of their research.
“Segmental bone fractures are a complex medical condition. These injuries cause great suffering to patients, long term hospitalization, repeated surgeries, loss of working days, and considerable costs to the health system.”
It sounds like he is talking about my brother!
The trouble was, like everyone else in medical research today, Gazit and Bae were helpless without a research grant. Almost everywhere, the news is grim about grant availability. About the best anyone can say is that the funding is “flat”, meaning just barely keeping up with inflation.
For instance, in 2011, osteoporosis (bone loss) received $179 million in National Institutes of Health (NIH) research grants– but only $141 million in 2014. This is worse than “flat”, a failure to keep up with inflation, but an actual cut: a loss of $38 million.
But thank the voters for the California Institute for Regenerative Medicine (CIRM) better known as the California stem cell program! Begun as the citizens’ initiative, Proposition 71, CIRM was and is going strong.
Dr. Gazit won a “translational” grant from the cell program, and Bae joined him as the clinical lead of the project. Translational is the word everybody wants to hear, because it means patients will benefit sooner. Basic science must come first, the foundation of fact on which everything depends. Basic science involves lots of microscopic studies, cells and lab rats. But translational? That “aims to improve the health of individuals and the community by “translating” findings into diagnostic tools, medicines, procedures…”
As Dr. Gazit said:
“My group has previously shown that stem cells from human bone marrow, engineered with a bone-forming gene, can lead to complete repair of segmental fractures.
“However, such an approach requires several steps, which could complicate…the pathway to clinical use. An alternative approach would be to gene-modify stem cells that already reside in the fracture site.
“We were the first to show, in a rodent model, that a segmental bone defect can be completely repaired by recruitment of stem cells to the defect site followed by direct gene delivery…we aim to…promote this project to clinical (human) studies.
Note: in a phone interview, Dr. Gazit explained that no stem cells would be injected into the body. Instead, a collagen scaffold (sponge-like material) would be inserted at the wound area. This would attract the body’s own stem cells. When enough of them had arrived on the site, (and there was a way to keep track of how many arrived) then a specific gene would be injected. In order to get the gene into the cells, Dr. Gazit would use an “ultrasound machine that almost every cardiology department has”.
“…the gene would trigger the cells to regenerate the bone that had been lost to trauma or cancer.
“…We will test the efficiency (and safety) of the method in repairing large bone defects. If successful, we will be able to proceed to FDA approval towards first-in-human trials.
“…This project could lead to the development of a simple treatment for massive bone loss. Such a treatment will benefit the citizens of California by reducing loss of workdays, duration of hospital stays, operative costs–
“–and by improving quality of life for Californians with complex segmental bone fractures.”
People like my brother.