TMC PULSE

t m c » p u l s e | o c t o b e r 2 0 1 6 26 Originally, Papanna, the principal investigator and an assistant profes- sor in the Department of Obstetrics, Gynecology and Reproductive Sciences at McGovern Medical School at The University of Texas Health Science Center at Houston and a maternal-fetal medicine specialist at The Fetal Center at Children's Memorial Hermann Hospital, was interested in using amni- otic membrane from the placenta to seal fetal membranes—the layers of the amniotic sac—after surgeries in utero. He and Mann flew to Miami to meet with expert ophthalmologist Scheffer C.G. Tseng, M.D., Ph.D., who was using a human amniotic membrane patch to repair corneas. After spending a week in his center, the two were even more impressed at its regenerative properties. What makes the material so "magi- cal," as Papanna puts it, is a compound called heavy chain hyaluronic acid/pen- traxin3, which initiates natural regen- eration of the tissues at the repair site, rather than healing by scar formation. The distinction is important in spina bifida repair since one creates a healthy, biologically compatible environment while the other often leads to scarring of the spinal cord to the repair site. This can lead to loss of bladder and motor function later in life. If scarring occurs, further surgeries are required to remove the scar tissue and protect the spine. "The molecule is the same one that is present around the egg of every woman who ovulates every month, in the lining of the womb and the placenta. This is essential to maintain normal reproductive function," Papanna said. "Nature has created a solution, and we have harnessed it to our benefit." But this wasn't the fairytale ending Papanna and Mann had hoped for. Despite its phenomenal healing prop- erties, the amniotic membrane patch was paper-thin and flimsy, making it difficult to work with. "If the site gets infected, the baby dies," explained Kenneth Moise, M.D., director of the Fetal Intervention Fellowship Program at McGovern Medical School and co-director of The Fetal Center at Children's Memorial Hermann Hospital. "It's covering the spinal cord, so it has to be a watertight seal—CSF [cerebrospinal fluid] can't leak out and infections can't come in." Unfortunately, every time Papanna practiced his stitches on the delicate material, it tore. So he looked to the umbilical cord, which contains the same "magical" molecules as the amni- otic membrane, but is thicker and far more pliable. "It was so obvious," Papanna said. "The umbilical cord has the same regenerative properties." Success stories Mann and Papanna contacted Tseng, who created a new patch and sent it back to them for testing. After suturing multiple chicken breasts and inject- ing blue dye as a proxy for cerebral spinal fluid, Papanna and Mann were satisfied that it could provide the watertight seal necessary for spina bifida repair. Papanna's lab studied its performance in animal models and he was granted approval from the FDA for clinical use in three cases. He and a team of surgeons including Moise, Kuojen Tsao, M.D., co-director of the Fetal Center at Children's Memorial Hermann Hospital and an associate From left to right, Ramesha Papanna, M.D., M.P.H.; Lovepreet K. Mann, M.B.B.S.; Stephen Fletcher, D.O., associate professor in McGovern Medical School's Department of Pediatric Surgery and pediatric neurosurgeon affiliated with Memorial Hermann Mischer Neuroscience Institute at the Texas Medical Center and Children's Memorial Hermann Hospital; and Kenneth Moise, M.D., director of the Fetal Intervention Fellowship Program at McGovern Medical School and co-director of The Fetal Center at Children's Memorial Hermann Hospital. professor at McGovern Medical School's Department of Pediatric Surgery, and pediatric neurosurgeon Stephen Fletcher, D.O., an associ- ate professor in McGovern Medical School's Department of Pediatric Surgery, performed the first surgery in July 2015. A second case was performed a few months later, and the results of the two surgeries were published in Obstetrics and Gynecology in July of this year. So far, they have been success stories. In both cases, the surgeries went well and the babies were born at 37 and a half weeks, just three weeks shy of full term. At birth, the patch was still in place and there were no signs of leakage or fluid inside. Moreover, both babies retained lower limb function as well as normal bowel movements. The one peculiarity was that, at birth, the site had not yet regenerated—it was semi-translucent, and when Papanna tapped the baby's head, he could see the cerebrospinal fluid underneath the patch. Within a few weeks, however, the skin grew into the patch exactly as expected. "Every day you could watch the blood vessels and the tissues grow closer together," Papanna said. "It was incredible." A third case was completed and as the months pass, all three babies con- tinue to exhibit normal leg movement and bladder control and no need for fur- ther repair. The true test will come with time, but already the patch is showing promise as the next big advancement in fetal surgery: whereas the MOMS Trial demonstrated that fetal surgery could vastly improve outcomes in mobility and neurological development, this patch could take the procedure a step further, resulting in an even more improved outcome for children with spina bifida. Perhaps, in the future, there will be no more need for surgical revisions, no additional repairs, few if any symptoms. An entirely normal childhood. "People are trying stem cells and different 'off the shelf' patches, but this patch is doing more than any of the others," Mann said. "It's helping with regeneration of existing skin. It's cre- ating organized growth of tissues, and the body doesn't reject it. Even more, its source is abundant since the umbilical cord from every pregnancy could pro- duce a new patch."

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