There is now hope for girls afflicted with a rare genetic condition called Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome which causes underdeveloped or absent vaginas. In a revolutionary application of regenerative medicine, four teenage girls have received vaginal organs that were engineered in the laboratory with the girls’ own cells then successfully implanted. The research team at Wake Forest Baptist Medical Center, led by Anthony Atala, M.D., director of the Institute for Regenerative Medicine, published the results of their pilot study in today’s issue of The Lancet. The study demonstrates that functional vaginal organs can be constructed in a laboratory, and successfully implanted in humans. The applications of the technology extend to patients who need vaginal reconstructive surgery, such as in cancer, injury, or congenital abnormalities.
So how was it done?
Because previous attempts at reconstruction using non-vaginal tissue met with complications, the researchers used a small biopsy of muscle and epithelial cells from the patients’ own external genitalia. The cells were grown in the lab, and then placed on a scaffold (think: topiary) made of a biodegradable material. The scaffolds were shaped into vaginas and tailored to fit each patient, then allowed to grow for a while in an incubator. Previous experimentation has established that once scaffolds bearing cells are placed in the body, blood vessels and nerves will grow around the implant and the implanted cells will form tissue. The biodegradable scaffold is eventually absorbed by the recipient as the cells develop into a new organ. Laboratory analysis conducted after the engineered vaginas were successfully implanted showed the organ had developed three layers of vaginal tissue, with no visible distinction between the original tissue and the engineered implant. The team found no long-term postoperative complications from the surgery.
The girls who received the vaginal implants between 2005 and 2008 were followed for several years. Yearly vaginoscopys showed no abnormalities: as much as eight years later, the vaginas were functioning normally, as assessed by internal exam, tissue biopsy, and MRI scans. The tissue was examined immunohistochemically, using fluorescently-tagged antibodies that binds to specific tissue markers; this assay showed normal smooth muscle and epithelial cells. Even better, the girls showed normal sexual function as assessed by a Female Sexual Function Index: parameters measured included desire, lubrication, arousal, satisfaction, orgasm, and no pain during intercourse.
Before developing the capacity to grow organs in the lab from the patient’s own cells, people in need of tissues or organs were forced to rely on transplants from autologous (other) donors. Unfortunately, this presented difficulties in the form of tissue rejection or immune reactions; also, patients often had to wait for years for donated organs. The successful implantation of vaginas engineered in the laboratory has built upon a considerable amount of previous research. Preceding this pilot study, the research team built vaginas in the lab for mice and rabbits while developing the idea of growing cells on scaffolds. Beginning in 1998, the team pioneered the world of regenerative medicine by implanting the first laboratory-grown organs into humans, starting with the successful implantation of replacement bladders in nine children. The team also implanted laboratory-grown urethras into boys. Research teams around the world are experimenting with the regeneration and implantation of other organs: in 2011, a synthetic trachea grown from a patient’s own stem cells in London was implanted in the patient in Stockholm. More recently, UK scientists have been growing blood vessels, noses, and ears in the laboratory. Future directions for the Atala’s researchers at Wake Forest Baptist Medical Center will involve expanding their clinical experience with more implant recipients, and comparing their results with surgical procedures already established. Besides vaginas, Atala’s team is also going to try growing as many as 20 other organs and tissues, including hearts and blood vessels in the laboratory.
By Laura Prendergast