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Rewriting Life

Healing Bone with Stem Cells

New techniques to boost survival of adult stem cells could improve surgeries for severe fractures.

Implantable materials that grab stem cells and spur their growth and survival could improve bone-healing surgeries. Linda Griffith and her colleagues at MIT have created a new tissue-engineering material that could help cells survive the harsh transplant environment–a key step in cell-transplant therapies. Scientists are now testing the material in animals to see how well it can help heal fractures.

Broken bones: New methods to boost cell survival after transplant could help heal severe fractures.

“Creating instructional biomaterials like this is an entirely new way of thinking about what could be put in the human body,” says Richard Lee, a cardiologist and scientist at Harvard Medical School and Brigham and Women’s Hospital, in Boston. “It could become an important component of regenerative medicine.”

Patients with severe fractures that can’t heal on their own typically undergo a painful bone biopsy in which a bone fragment is removed from the hip and then transplanted onto the site of the wound. But improvements to an alternative procedure developed in the past few years could soon make this process obsolete. In the procedure, orthopedic surgeons withdraw bone marrow (which contains bone-forming stem cells) from the patient and then process and transplant those cells onto the fracture without the need for bone biopsy.

Some 40,000 people have already undergone the procedure, but scientists say the technique could be improved by increasing the survival and proliferation of the transplanted cells. “Cells experience a very harsh environment when first transplanted,” says George Muschler, an orthopedic surgeon at the Cleveland Clinic, in Ohio, who pioneered development of the bone-marrow transplant technique. “There is little oxygen, it’s very acidic, and there are inflammatory factors that might trigger cell death.” In addition, only about one in every 20,000 bone-marrow cells is a bone-producing stem cell, making survival of those cells particularly critical.

A new material that stops cell-death signals in their tracks could help. Over the past decade, Griffith and her colleagues have developed materials called comb scaffolds that have been employed for a variety of tissue-engineering uses, such as growing new blood vessels. The comb consists of a Plexiglas backbone studded with molecular tethers that can hold different protein growth factors at their tips. In their latest round of experiments, the researchers modified the scaffold to hold epidermal growth factor (EGF) molecules, a protein that plays a role in growth and differentiation of many cells, including stem cells. According to research published earlier this year in the journal Stem Cells, adult stem cells grown on the EGF scaffolds were better able to survive. And preliminary evidence suggests that the scaffold also boosts cell proliferation, potentially increasing the number of cells available to make new bone after transplantation.

Muschler, an orthopedic surgeon and Griffith’s collaborator, is now testing the scaffold in animal models to see how well it heals fractures. And Griffith is planning additional experiments with human stem cells to explore how different proteins on the scaffold might encourage these cells to differentiate into bone. “We want to figure out step by step how to use marrow more effectively in the clinic,” she says. Their ultimate goal is to be able to extract bone marrow from a patient and, while still in the operating room, filter the extract through a specially designed scaffold that preferentially grabs bone-forming stem cells and boosts their growth and survival. The cells can then be directly implanted into the patient.

“The field is just beginning,” says Lee. “It will be exciting to see how much ability this gives us to change materials, and how they react with the body.”

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