ADIPOSE STEM CELLS TRANSPLANTATION IN A RAT TRAUMATIC BRAIN INJURY MODEL

Pluripotent mesenchymal stem cells (MSCs) are thought to participate in tissue repair through trophic support and immunomodulation when transplanted into damaged tissues. Adipose tissue is considered as an attractive source of MSCs, generating the so called adipose stem cells (ASCs). The present study examines host brain responses induced by ASCs intracerebroventricular (ICV) transplantation in an animal model of traumatic brain injury (TBI). For this, 3-month old rats received succesively localized TBI and ICV transplantation of Venus+ ASCs. Normal rats transplanted with ASCs and TBI rats transplanted with medium, were used as controls. Survival, spatial distribution and integration of ASCs in the host parenchyma were examined at one and six weeks post transplantation. Proliferative activity of both transplanted ASCs and endogenous reactive cells, focusing on hippocampal radial glia like neural stem cells (NSCs), was explored with antibodies for Ki67 and BrdU. Interactions of transplanted ASCs with innate brain inflammatory cells were assessed with the markers Iba-1 and GFAP, respectively. According to the results obtained, ASCs one week after their transplantation exhibit proliferative activity, integrate into brain parenchyma migrating mainly to the periventricular area, whereas some of them acquire morphology of mature cells with ramified processes. ASCs migration was more profound six weeks after their ICV transplantation, as they reach TBI site through white mater tracks and gather around pre- existing or newly formed blood vessels. Both presence of ASCs and TBI have a positive impact on hippocampal NSCs proliferation bilaterally. In addition, ASCs enhanced brain inflammatory responses with no existing evidence of their phagocytocis or destruction. As inflammation can participate in both beneficial and detrimental outcomes, the findings of this study suggest that ASCs transplantation may contribute to the acceleration of host brain repair mechanisms.