Flesh and Bone
Leukemia survivor creates artificial bone marrow, brain tumor in the hunt for cures.
A “high-stakes situation” is how Brendan Harley describes the perilous position he found himself in 19 years ago. When he was only a junior in high school, he was diagnosed with a particularly virulent form of leukemia, and he faced the harrowing ordeal of a bone marrow transplant.
This experience was pivotal and formative, inspiring his life’s work. Today, Harley is an LAS professor of chemical and biomolecular engineering, and he and his team develop “biomimetic” engineered tissues. This work includes an artificial bone marrow that might someday help improve the odds for leukemia patients. He is also working on implantable biomaterials to regenerate the connections between bone and tendons or cartilage, as well as an artificial brain tumor biomaterial to screen for effective therapies to treat virulent forms of glioma—a type of brain tumor.
While being treated for leukemia, Harley was in and out of the hospital throughout his junior and senior years of high school. He says he underwent myeloablative therapy, with high doses of chemotherapy and full-body radiation. While this therapy effectively treated his leukemia, it also destroyed his entire blood and immune (hematopoietic) system, so he had to follow up the radiation and chemotherapy with a risky bone marrow transplant.
Even today, almost two decades since his treatment, the survival rate after bone marrow transplants is about 50 percent. But Harley found a good match in a bone marrow donor—his own brother.
“I was incredibly lucky,” he says, “because there are so many things that can go wrong when you’re treated for any kind of cancer.”
After going through the rounds of chemotherapy leading up to his transplant and then the transplant itself, Harley was kept in isolation throughout his entire senior year of high school as his immune system recovered. Growing up outside of Boston, he was treated at a teaching hospital affiliated with Harvard Medical School; this put him into contact with many young medical students and interns who were training to perform procedures such as taking his blood pressure and bone marrow biopsy. As they did, he found that many of them had similar interests in engineering and biology like him, and were applying those interests in the hospital.
This experience in the hospital pushed him in the direction of biomedical engineering work. But he was also inspired by a photograph in the Boston Globe of the infamous “ear mouse.” Medical researchers had developed a way to integrate a biomaterial scaffold shaped like a human ear, and they seeded it with cow cells onto the back of a mouse to grow an artificial ear. The Vacanti mouse, as it was technically called, left Harley imagining how he might be able to grow organs and tissues in the future for a wider range of human diseases.
Therefore, it was only fitting that when Harley came to Illinois in 2008, one of the first projects he embarked upon was an effort to develop artificial bone marrow.
The bone marrow transplant relies on getting a rare population of donor cells—hematopoietic stem cells—to successfully produce a new blood and immune system within the recipient. As he knew from experience, one of the great risks in a bone marrow transplant is whether the donor cells successfully “home” and “engraft” into a patient’s bone marrow.
The donor’s stem cells are injected into the recipient’s bloodstream and must “home” back to the marrow—moving into the bone marrow cavity. They then must “engraft,” continuously producing functional hematopoietic cells for the remainder of the recipient’s life. However, only a small fraction of these hematopoietic stem cells will successfully home and engraft—one reason for the high mortality rates associated with bone marrow transplants. That’s also why it is important to have large numbers of donor stem cells with which to work.
One of the goals of the artificial bone marrow is to develop a system able to significantly expand the number of available stem cells. To do this, Harley’s team has created a 3-D artificial culture that mimics the environmental conditions of bone marrow. Using this environment to nurture hematopoietic stem cells, they hope to be able to generate larger numbers of donor cells as well as explore the use of specialized helper cells, also found in the marrow, to improve engraftment. They believe their artificial bone marrow can even be used as a platform for studying the process of homing and engrafting—events too rare to observe directly.
Another significant biomaterial project in the Harley laboratory is studying non-uniform tissue between tendons and bone. Tendons are connected to bone by an intermediary zone, in which the tissue progressively changes from tendon to bone. The problem, he says, is that after an injury, in which the tendon tears away from the bone, this intermediary zone is lost during current treatments and the risk of re-injury is great.
“Our goal is to create a material that can be inserted between the tendon and the bone, where the tendon is torn off, to facilitate biological healing,” he says.
Harley’s team also hopes to apply the biomaterial fabrication techniques they have developed for this project to reconstruct craniofacial defects. For example, by working with Matthew Wheeler in animal sciences, they hope to create an approach to regenerate tissue lost to soldiers from blast injuries. The types of injuries suffered by military personnel have changed substantially, he says, with today’s soldiers experiencing—and surviving— traumatic blast injuries to the face at higher rates than ever before.
The biomaterial they develop may even be used someday to treat civilian populations, such as to replace jaw tissue removed during cancer treatments. This biomaterial has “come along quite a bit due to the strength of our collaborative team,” he says, and they are about to begin preclinical trials to demonstrate its efficacy.
The third major project coming from Harley’s lab is an artificial brain tumor. Cancer cells isolated from the patient may one day be cultured in an artificial brain tumor so that doctors can test and refine treatment protocols in real time. That way, the treatments can be targeted to a person’s specific cancer cells.
Right now, Harley is working with Mayo Clinic in studying glioblastoma, one of the most deadly forms of brain cancer, but this system could eventually be adapted to test treatments on a wider range of cancers.
With such a unique combination of personal and professional experiences, Harley has become a regular speaker at Relay for Life events and other programs organized by the American Cancer Society (ACS).
“I have seen both sides,” he says. “I talk as someone who had been a patient and is now a researcher. I can also speak to the fact that progress in cancer research cannot be measured in days or months, but rather requires sustained commitment to research excellence. Some cancers that were almost ubiquitously fatal a generation ago are now regularly treated.”
Harley says he is a committed supporter of ACS because he has benefited from their work firsthand. Some of the earliest funding for bone marrow transplant research came from the ACS in the 1950s and ’60s. The ACS also focuses on supporting the research of young investigators, and the organization is proud to have funded the early work of more than 40 Nobel Prize winners.
“My dual experience as survivor and bioengineer is something I reflect on a lot,” he says. “I don’t necessarily attack research problems any harder because of the treatment processes I went through. But it was an important part of my life; it shaped my life, and everything I do is impacted by it.
“It’s a part of me,” he says.
By Doug Peterson