EXPERIMENTAL STUDY ON THE EFFECT OF BONE MARROW MESENCHYMAL STEM CELL-DERIVED EXOSOMES ON NEUROVASCULAR REGENERATION AND REPAIR AFTER BRAIN INJURY

Jiehua Ma¹, Lihong Tang², Min Cao³, Wenyue Bu¹, Yu Zhao^1*

¹Department of Anatomy, HeBei North University, Zhangjiakou 075000, Hebei Province, China - ²Department of Obstetrics and Gynecology, Beijing Liangxiang Hospital, Beijing 102401, China - ³Department of Pathology, Beijing Liangxiang Hospital, Beijing 102401, China

Objective: To investigate the effect of exosomes (EXO) derived from bone marrow mesenchymal stem cells (MSCs) on neurovascular regeneration and repair after brain injury.

Methods: Forty-five male SD rats were randomly divided into three groups (sham-operated, traumatic brain injury (TBI) and EXO) with 15 rats in each group. Animals from the sham-operated and TBI groups were injected with 5 μL PBS into the left ventricle after modelling, and those from the EXO group were injected with 5 μL EXO into the left ventricle after modelling (day 0). The  modified neurological function score (MNSs), microvessel density (MVD) and vascular endothelial growth factor (VEGF) optical density (IOD) values around the brain injury focus were compared on days 1, 3 and 7 following injection. The protein expression levels of VEGF, vascular endothelial growth factor receptor-1 (VEGFR-1) and VEGFR-2, as well as the occurrence of apoptosis, were compared on day 7.

Results: The MNSs of the TBI and EXO groups were significantly higher than those of the sham-operated group on days 1, 3 and 7 (P<0.05). The MNSs of the EXO group was significantly lower than that of the TBI group (P<0.05) on day 7. The MVD of the TBI group was significantly lower than that of the sham-operated group (P < 0.05) on days 1, 3 and 7; the MVD of the EXO group was significantly higher than that of the TBI group (P<0.05). The VEGF IOD of the TBI group was significantly higher than that of the sham-operated group on days 1, 3 and 7 (P<0.05); the VEGF IOD of the EXO group was significantly higher than that of the TBI group on days 1 and 3 (P<0.05). The number of apoptotic cells in the TBI group was significantly higher than that in the sham-operated group (P<0.05). The expression levels of vegr, VEGFR-1 and VEGFR-2 in the TBI group were significantly higher than those in the sham-operated group. The expression levels of vegr, VEGFR-1 and VEGFR-2 in the EXO group were significantly higher than those in the TBI group (P<0.05). The number of apoptotic cells in the EXO group was significantly lower than that in the TBI group (P < 0.05).

Conclusion: Bone marrow MSC-derived exosomes can effectively improve the neurologic impairment of TBI rats, as well as promote the regeneration and repair of nerve vessels, which may be related to the increase of MVD and VEGF expression around the brain injury.