How did you become interested in making tissues?
GRAYSON: I used to play a lot of soccer and I had a lot of sports injuries. In one of my visits to the orthopedic surgeon, I began to take an interest in orthopedics. At that time I was getting an engineering degree, so the engineering and the medicine kind of melded together in this scenario.
Besides fixing your own sports injuries, why are you engineering bone and cartilage?
GRAYSON: One of the visions of tissue engineering is to use biological replacements rather than synthetic replacements for surgeries like hip and knee replacements. The ultimate goal would to be able to put into a person a biological graft rather than metal or plastic, since these synthetic materials cannot fully ‘regenerate’ the affected tissues. Also, with people living longer, more active lives, these synthetic grafts may need to be revised one or two times within the person’s lifetime. For biological grafts, preferably we would use a patient’s own cells to regenerate tissue for that repair. The risks associated with using transplanted cells from other donors are disease transmission and immune rejection. The tissue engineering approach which uses the patient’s own cells helps to circumvents all these issues.
Your lab uses stem cells to make these tissues. How is that done?
GRAYSON: We use adult stem cells; typically they are fat or bone marrow derived cells, which are able to give rise to bone, cartilage and vascular cells. We put these stem cells in three-dimensional scaffolds (made from naturally occurring biomaterials)–not in Petri dishes, because cells in the body do not grow on flat surfaces. We incubate these cells in bioreactors to provide the environment for guiding these cells to form functional tissue. The bioreactor is essentially a small incubator that controls temperature, pH, adds growth factors and can give physiological signals by controlling all the mechanical and biophysical forces to help guide cell development. We try to mimic what happens in the body that will result in tissue growth. The idea is to have these tissues grown for several weeks outside the body to give rise to a “functional tissue.”
Why did you choose to use adult stem cells?
GRAYSON: They are more readily available. They have an advantage over embryonic stem cells in having fewer ethical concerns, which seem to hinder the potential applications of embryonic stem cells. But, also from a scientific perspective, they are easier to control. Embryonic stem cells can form any tissue type but they continue to grow and form tumors if implanted in the body. We don’t have this problem if we use adult derived stem cells. They also provide us with the ability to use a patient’s own cells for therapeutic purposes.
How far are we towards being able to have our own tissues repair our injuries?
GRAYSON: Most of the work we’ve done so far has been performed outside of living organisms, but we are starting to work on animal models. We are erring on the side of caution and taking a scientifically rigorous approach. Lots of work has been done where stem cells have been used for a number of different ’therapies’. And in some cases people are just injecting cells inside of patients to see what happens. It’s great if you see an improvement, but you don’t know why these improvements occur. While we have this huge vision about what we can accomplish with stem cells, we try to take a step-by-step approach and be fairly rigorous as to understand the mechanistic approach before we apply this in the clinic.
Warren Grayson on creating bone grafts from a patient's own stem cells: