Systemic treatment with human amnion epithelial cells after experimental traumatic brain injury

Abstract

Systemic administration of human amnion epithelial cells (hAECs) was recently shown to reduce neuropathology and improve functional recovery following ischemic stroke in both mice and marmosets. Given the significant neuropathological overlap between ischemic stroke and traumatic brain injury (TBI), we hypothesized that a similar hAEC treatment regime would also improve TBI outcomes. Male mice (12 weeks old, n ​= ​40) were given a sham injury or moderate severity TBI by controlled cortical impact. At 60 ​min post-injury, mice were given a single tail vein injection of either saline (vehicle) or 1 ​× ​106 hAECs suspended in saline. At 24 ​h post-injury, mice were assessed for locomotion and anxiety using an open field, and sensorimotor ability using a rotarod. At 48 ​h post-injury, brains were collected for analysis of immune cells via flow cytometry, or histological evaluation of lesion volume and hAEC penetration. To assess the impact of TBI and hAECs on lymphoid organs, spleen and thymus weights were determined. Treatment with hAECs did not prevent TBI-induced sensorimotor deficits at 24 ​h post-injury. hAECs were detected in the injured brain parenchyma; however, lesion volume was not altered by hAEC treatment. Robust increases in several leukocyte populations in the ipsilateral hemisphere of TBI mice were found when compared to sham mice at 48 ​h post-injury; however, hAEC treatment did not alter brain immune cell numbers. Both TBI and hAEC treatment were found to increase spleen weight. Taken together, these findings indicate that—unlike in ischemic stroke—treatment with hAEC was unable to prevent immune cell infiltration and sensorimotor deficits in the acute stages following controlled cortical impact in mice. Although further investigations are required, our data suggests that the lack of hAEC-induced neuroprotection in the current study may be explained by the differential splenic contributions to neuropathology between these brain injury models.