TOP 75 - Posthemorrhagic Vascular injury and recovery after Stem Cell administration for Germinal Matrix (GM) Intraventricular Hemorrhage (IVH)

Publication Number: 3807.TOP 75

Adila Chamavaliyathil, Westchester Medical Center, New York, NY, United States; Shahajahan M. Kadage, Westchester Medical Center, Valhalla, NY, United States; Furong Hu, Boston Children's Hospital, Valhalla, NY, United States; Sulaymankhil Davud, New York Medical College, NYC, NY, United States; Mitchell S. Cairo, New York Medical College, Valhalla, NY, United States; Yanling Liao, New York Medical College, Valhalla, NY, United States; Govindaiah Vinukonda, New York Medical College, Valhalla, NY, United States; Edmund F.. La Gamma, Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, NY, United States

Background: Germinal matrix–intraventricular hemorrhage is a common problem of premature infants associated with white matter & diffuse brain injury plus neurodevelopmental disabilities. IVH is primarily a vascular disease resulting from rupture of fragile immature capillaries with injury to an underdeveloped blood-brain barrier resulting in inflammation & interruption of brain development. Clinically there are no effective neuroprotective strategies that enhance brain recovery. The concept of the ‘neurovascular unit’ has emerged as a paradigm for understanding the complex pathology of IVH; there is insufficient knowledge informing postnatal vascular pathology or recovery.

Objective: To determine whether human umbilical cord blood derived unrestricted somatic stem cells (hUSSC) can help recovery from CNS injury due to their capacity to adapt to a changing microenvironment as “living cell therapy” for IVH.

Design/Methods: We used a glycerol-induced preterm rabbit model of IVH (Vinukonda, Brain,133 (8): 2264, 2010) and injected a single dose of USSC (Dose:1X106, ICV 15uL each side; at post-injury d1 for 3d end points & 2 treatments on post-injury d1 & d3 for 7d endpoint studies. We assessed GM volume (mean surface area) & number of total blood vessel counted/10X image field using image-J software after IHC staining using CD31 antibody.We compared 4 study groups:full term, preterm, preterm+IVH,& preterm+IVH+USSC injected pups (data: ẍ ± SD).

Results: We found a significant decrease in the total number of blood vessel density in the sub-ependymal GM in preterm pups compared with full term (118±16 vs 168±19 per 10X field; P< 0.005, n=7&5), and in preterm IVH vs preterm controls (63±20 vs 118±16; p< 0.005, n= 6&7). USSC treated pups showed a significant recovery of vascularity compared with IVH (88±9 vs 63±20; p< 0.05, n=4&6). Morphologically, we observed longer blood vessels in control and USSC treated pups compared with few in IVH pups.The IVH pups also showed a reduction in GM volume when compared with controls (6.5±1.5 vs 9.4±1.3 p< 0.005, n= 6&7).After a single dose of USSCs in IVH pups, there was some recovery of volume & this effect was no longer significant vs control volume at 3d; USSC Rx did not achieve significance vs IVH alone (9.1± 2.7 vs 6.5±1.5, p=0.08, n=6&4). Evaluation of neuroglial changes in the neurovascular unit for its gene and protein expression assessments are in progress.

Conclusion: USSCs recover vascular growth in the GM after IVH. We speculate that this will help recover low tissue oxygen delivery and nutrient supply to further enable return of normal brain maturation.