Tissue engineered vagina’s function normally over eight years

Researchers from Wake Forest University in Winston-Salem and the Metropolitan Autonomous University in Mexico City biopsied cells from the women and were able to use a biodegradable scaffolds to then build the vagina in the lab. The organs were then implanted in each patient.

A woman with MRKH will often not develop a uterus or a full vagina, though external genitalia is unaffected by the disorder, which often means the syndrome is not diagnosed until the patient is in her late teens. Before the study, patients were limited to surgical options to recreate that vaginal canal. The disorder affects approximately one in 4,500 female births, according to the National Institutes of Health. Therefore the condition effects over 500,000 women. There were about 131 million births in 2013. Therefore about 14400 births had this condition.

A research team led by Anthony Atala, M.D., director of Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine, describes in the Lancet long-term success in four teenage girls who received vaginal organs that were engineered with their own cells.

“This pilot study is the first to demonstrate that vaginal organs can be constructed in the lab and used successfully in humans,” said Atala. “This may represent a new option for patients who require vaginal reconstructive surgeries. In addition, this study is one more example of how regenerative medicine strategies can be applied to a variety of tissues and organs.”

New Technology Generates Lab-Grown Organs

In the eight years after the original operation, researchers found that the subjects reported normal sexual function and that the engineered organs remained structurally and functionally normal.

The Lancet – Tissue-engineered autologous vaginal organs in patients: a pilot cohort study

“Tissue biopsies, MRI scans and internal exams using magnification all showed that the engineered vaginas were similar in makeup and function to native tissue, said Atlantida-Raya Rivera, lead author and director of the HIMFG Tissue Engineering Laboratory at the MRKH in Mexico City, where the surgeries were performed.

In addition, the patients’ responses to a Female Sexual Function Index questionnaire showed they had normal sexual function after the treatment, including desire and pain-free intercourse.

The organ structures were engineered using muscle and epithelial cells (the cells that line the body’s cavities) from a small biopsy of each patient’s external genitals. In a Good Manufacturing Practices facility, the cells were extracted from the tissues, expanded and then placed on a biodegradable material that was hand-sewn into a vagina-like shape. These scaffolds were tailor-made to fit each patient.

About five to six weeks after the biopsy, surgeons created a canal in the patient’s pelvis and sutured the scaffold to reproductive structures. Previous laboratory and clinical research in Atala’s lab has shown that once cell-seeded scaffolds are implanted in the body, nerves and blood vessels form and the cells expand and form tissue. At the same time the scaffolding material is being absorbed by the body, the cells lay down materials to form a permanent support structure – gradually replacing the engineered scaffold with a new organ.

Followup testing on the lab-engineered vaginas showed the margin between native tissue and the engineered segments was indistinguishable and that the scaffold had developed into tri-layer vaginal tissue.

Current treatments for MRHK syndrome include dilation of existing tissue or reconstructive surgery to create new vaginal tissue. A variety of materials can be used to surgically construct a new vagina – from skin grafts to tissue that lines the abdominal cavity. However, these substitutes often lack a normal muscle layer and some patients can develop a narrowing or contracting of the vagina.

The researchers say that with conventional treatments, the overall complication rate is as high as 75 percent in pediatric patients, with the need for vaginal dilation due to narrowing being the most common complication.

Before beginning the pilot clinical study, Atala’s team evaluated lab-built vaginas in mice and rabbits beginning in the early 1990s. In these studies, scientists discovered the importance of using cells on the scaffolds. Atala’s team used a similar approach to engineer replacement bladders that were implanted in nine children beginning in 1998, becoming the first in the world to implant laboratory-grown organs in humans. The team has also successfully implanted lab-engineered urine tubes (urethras) into young boys.

Summary

Background
Several disorders might require vaginal reconstruction, such as congenital abnormalities, injury, or cancer. Reconstructive techniques for which non-vaginal tissue is used can be associated with complications. We assessed the use of engineered vaginal organs in four patients with vaginal aplasia caused by Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS).

Methods
We invited to participate four consecutive patients who presented over a 3-year period with congenital vaginal aplasia due to MRKHS. Patients were aged 13—18 years. We obtained a vulvar biopsy of autologous tissue from every patient. We cultured, expanded, and seeded epithelial and muscle cells onto biodegradable scaffolds. The organs were constructed and allowed to mature in an incubator in a facility approved for human-tissue manufacturing. We used a perineal approach to surgically implant these organs. We recorded history, physical examination, vaginoscopy, serial tissue biopsies, MRIs, and self-administered Female Sexual Function Index questionnaire results for all patients, with a follow-up of up to 8 years.

Findings
We noted no long-term postoperative surgical complications. Yearly serial biopsies showed a tri-layered structure, consisting of an epithelial cell-lined lumen surrounded by matrix and muscle, with expected components of vaginal tissue present. Immunohistochemical analysis confirmed the presence of phenotypically normal smooth muscle and epithelia. The MRIs, which showed the extent of the vaginal aplasia before surgery, showed the engineered organs and the absence of abnormalities after surgery, which was confirmed with yearly vaginoscopy. A validated self-administered Female Sexual Function Index questionnaire showed variables in the normal range in all areas tested, such as desire, arousal, lubrication, orgasm, satisfaction, and painless intercourse.

Interpretation

Vaginal organs, engineered from the patient’s own cells and implanted, showed normal structural and functional variables with a follow-up of up to 8 years. These technologies could be useful in patients requiring vaginal reconstruction.

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