| Background: Cerebrovascular diseases, which include cerebral ischemia and hemorrhage, represent severe clinical events of central nervous system disorder. Until today, effective therapeutic strategy is still lacking as to the neurological deficits after the occurrence of these diseases. The advancement of stem cell technology bring about prospectives in the treatment of these disorders. The candidate of stem cells includes embryonic stem cells (ESC) as well as adult stem cells, among which, mesenchymal stem cells (MSC) seem to be a more promising one regarding their advantages over ESC and other type of adult stem cells like neural stem cells (NSC). It has been proven that MSC could be beneficial in the treatment of a variety of diseases in central nervous system, though the underlying mechanisms are still unknown. Umbilical cord tissue has been recently regarded as a rich and ideal source of MSC thus umbilical cord derived MSC (UC-MSC) are deserved to be investigated in the treatment of cerebrovascular diseases.Objective: This study was designed to determine if UC-MSC intracerebarl transplantation of UC-MSC could promote the recovery of neurological functions after middle cerebral artery occlusion (MCAO) and intracerebral hemorrhage (ICH) in rats, and meantime to analyze the potential mechanisms.Methods: UC-MSC were isolated by cocktail enzyme digestion of human umbilical cords, CM-DiI labeled passage 4-6 UC-MSC were injected intracerebrally into the MCAO or ICH rats. Neurological evaluation including mNSS and Morris water maze test were conducted every week after transplantation. The injured volume of MCAO and ICH rats were calculated at 14 days and 28 days post-transplantation, respectively. In addition, vascular density and pro-angiogenic factors VEGF and bFGF were detected at 7 days after treatment in use of specific antibodies. In ICH rats, infiltration of inflammatory cells, reactive oxygen species (ROS) level and matrix metalloproteinase (MMPs) activity were detected at 3 days after transplantation. We also evaluated angiogenic and neurogenic potentials of UC-MSC in vitro. Results: UC-MSC could differentiate into both vascular cells and neural cells in vitro. Rats of MCAO and ICH received UC-MSC treatment show significant improved neurological functions as revealed by mNSS and water maze test. In addition, at 7 days after injection, the vascular density around injured region was drastically increased in UC-MSC treated rats in both MCAO and ICH model as compared to PBS groups. In ICH model, UC-MSC treatment can inhibit the leucocytes infiltration and microglial activation, ROS production and MMPs activity around ICH region.Conclusions: Human UC-MSC could effectively accelerate the recovery of neurological function after cerebrovascular diseases, and the underlying mechanisms may be associated with their ability to promote angiogenesis and inhibit inflammation. |
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