Aimee G Kim

Tissue Engineering Strategies for Fetal Myelomeningocele Repair in Animal Models

Myelomeningocele (MMC), the most severe form of spina bifida, is a common and devastating malformation. Over two decades of experimental work in animal models have led to the development and clinical application of open fetal surgery for the repair of the MMC defect. This approach offers improved neurofunctional outcomes and is now a clinical option for the management of prenatally diagnosed MMC in selected patients. However, there are still opportunities for further improvement in the prenatal treatment of MMC. A less invasive approach would allow for an application earlier in gestation, with a reduction in maternal and fetal risks and the potential for reduced neurological injury. Tissue engineering offers a realistic and appealing alternative approach for the prenatal treatment of MMC. This review discusses the rationale for tissue engineering in MMC, addresses recent experimental progress and describes potential future directions.

The Intravenous Route of Injection Optimizes Engraftment and Survival in the Murine Model of In Utero Hematopoietic Cell Transplantation

In utero hematopoietic cell transplantation (IUHCT) has the potential to treat a number of congenital hematologic disorders. Clinical application is limited by low levels of donor engraftment. Techniques that optimize donor cell delivery to the fetal liver (FL), the hematopoietic organ at the time of IUHCT, have the potential to enhance engraftment and the clinical success of IUHCT. We compared the 3 clinically applicable routes of injection (intravenous [i.v.], intraperitoneal [i.p.], and intrahepatic [i.h.]) and assessed short- and long-term donor cell engraftment and fetal survival in the murine model of IUHCT. We hypothesized that the i.v. route would promote direct donor cell homing to the FL, resulting in increased engraftment and allowing for larger injectate volumes without increased fetal mortality. We demonstrate that the i.v. route results in (1) rapid diffuse donor cell population of the FL compared with delayed diffuse engraftment after the i.p. and i.h. routes; (2) higher FL and spleen engraftment at early prenatal time points; (3) enhanced stable long-term peripheral blood donor cell engraftment; and (4) improved survival at higher injectate volumes, allowing for higher donor cell doses and increased long-term engraftment. These findings support the use of an i.v. route for clinical protocols of IUHCT.

Amniotic Fluid Concentrations of Glial Fibrillary Acidic Protein Do Not Correlate with Prenatal Metrics in Fetuses with Myelomeningocele

Introduction: We investigated the correlation of amniotic fluid (AF) concentrations of glial fibrillary acidic protein (GFAP) with prenatal features of myelomeningocele (MMC) and neurodevelopmental outcome after fetal MMC (fMMC) surgery. Materials and Methods: AF was collected during fMMC surgery between December 2012 and November 2015. AF-GFAP concentration was determined by ELISA. Retrospective chart review identified the characteristics of the defect. Data regarding delivery and 1-year neurodevelopmental outcome was collected from The Childrens Hospital of Philadelphia fMMC Registry. Results: Eighty-two AF samples were collected from fMMC surgeries. Perinatal data were obtained from 77 subjects, and 1-year follow-up data from 65 subjects. GFAP concentrations were significantly elevated in MMC compared to myeloschisis (24.1 ± 2.9 and 10.3 ± 1.5 ng/mL; p < 0.0001). A larger percentage of subjects with myeloschisis defects delivered before their scheduled due date (myeloschisis 88.5%; MMC 55.0%; p = 0.003) and delivered at an earlier mean gestational age (34.6 ± 0.4 weeks, n = 26) compared to those with MMC defects (35.2 ± 0.4 weeks, n = 51) (p = 0.04). Discussion: AF-GFAP levels differentiate between MMC and myeloschisis, and raise interesting questions regarding the clinical significance between the 2 types of defects.