Note: This is the first in CREA's occasional series of interviews with workers in the field of aging.
Pam Chitamitara
UCB Undergraduate Researcher
The prospect of long-term organ storage through cryopreservation may be a step closer to reality, thanks to work in progress by graduating Cal senior Pam Chitamitara. CREA spoke with Chitamitara at the recent UCB undergraduate biology research symposium, where she presented a poster.
Currently, organs destined for transplant have a shelf life of "a
matter of hours" outside the body, says Chitamitara. One possible
method of preservation is to freeze the organs in liquid nitrogen,
preventing decay. But total freezing of tissue is not currently
feasible due to a serious side-effect: ice crystals form and penetrate
through cells, cleaving the tissue and causing irreparable
damage. Although this damage can be modulated by gradual freezing, the
organs are still nonfunctional after thawing.
Chitamitara sought to test an alternative solution: limiting the amount of damage that ice could do in the first place. Working with advisors Natalya Lyubynska and Dr. Paola S. Timiras, along with researchers at Biotime, Inc., Chitamitara collected and cultured fibroblast cells from a large number of organs in Syrian hamster. She then added several protective chemicals, including dimethylsulfoxide (DMSO), to the cells and froze them. Once thawed, the chemically treated cells showed significantly greater viability versus untreated controls, with the best results obtained from fibroblasts of the lung, kidney, and spleen.
How does DMSO prevent damage normally caused by freezing? The answer, as Chitamitara explains it, is quite simple: "Water molecules are drawn to the molecules of DMSO, and away from tissue. That limits the amount of damage water can do to the tissue."
Limiting that damage may be the key to eventual long-term organ preservation and reduction of the currently-sizeable transplant waiting lists in the U.S. According to the annual report of the Scientific Registry of Transplant Recipients, 46% of all organs donated in 2002 were not recovered for transplantation. A significant cause of non-recovery (12% of cases, accounting for 2,537 organs) is that no suitable recipient could be found. Longer preservation of these donor organs would improve recovery rates and help the thousands of Americans, particularly elderly Americans, in need of transplants.
Chitamitara believes that Cal was the right place for her to do her undergraduate research. "I was satisfied with the level of support I received from the University and from Biotime. There were always enough animals on hand." At the same time, however, one gets the impression from speaking with her that this project might benefit from a more integrated approach. "There are so many different things that could be done based on this work, and we just can't do them all," she said. For example, work at the molecular level, such as an assay of the extent of the intracellular damage still caused by freezing DMSO-treated cells, could yield results to improve the efficacy of treatment.
What we do know about organ cryopreservation indicates that many biological challenges remain. For one thing, some of the chemicals used in this study are toxic to cells in concentrations only a bit larger than the ones Chitamitara used. For another, she says, "I don't think anyone's tried this with human cells yet."
But Chitamitara remains optimistic. After submitting this work for publication, she plans a career in medicine. "I am interested in doing research part-time, but my primary goal is to practice pediatrics," she told us. Should organ cryopreservation become a reality, it will certainly give hope to her future patients in need of transplants.