Intracerebral and Intravenous Transplantation Represents a Favorable Approach for Application of Human Umbilical Cord Mesenchymal Stromal Cells in Intracerebral Hemorrhage Rats
Jiang Xie, Bin Wang, Lian Wang, Fang Dong, Gang Bai, Yongjun Liu
Alliancells Key Institute of Stem Cells and Translational Regenerative Medicine, Tianjin AllianStemcell Biotech Co., Ltd., Post-Doctoral Research Station, Tianjin, China (mainland)
Med Sci Monit 2016; 22:3552-3561
Available online: 2016-10-05
Intracerebral hemorrhage (ICH) is one severe subtype of stroke, with a very complex pathology. Stem cell-based therapy holds promising potential in the treatment of neurological disorders. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have a therapeutic effect in recovery from brain damage following ICH. The aim of this study was to identify an effective and convenient way of using UC-MSCs in the ICH rat model.
MATERIAL AND METHODS: CM-DiI-labeled human UC-MSCs were transplanted intracerebrally or intravenously into collagenase VII-induced ICH rat models. Neurological function was evaluated before ICH and at 0, 7, 14, 21, and 28 days after treatment. ICH rats were sacrificed to evaluate the injury volume. Neurogenesis and angiogenesis and vascular areas were investigated using microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and 4’,6-diamidino-2-phenylindole (DAPI) immunohistochemistry at two weeks after transplantation.
RESULTS: The intracerebral and intravenous administration of UC-MSCs both resulted in significant improvement in neurological function and decrease in injury volume of ICH rats. Transplanted UC-MSCs were chemotactic in vivo and showed a predominant distribution around the ICH region. In addition, UC-MSCs could integrate into the cerebral vasculature in both groups.
CONCLUSIONS: Both intracerebral and intravenous administration of UC-MSCs could have a favorable effect on recovery of neurological function in ICH rats, although the fundamental mechanisms may be different between the two groups. Our data suggest that intravenous implantation of UC-MSCs could serve as a favorable approach for cell-based therapy in central nervous system (CNS) diseases according to clinical needs.
Keywords: Angiogenesis Inducing Agents, Human Umbilical Vein Endothelial Cells, Intracranial Hemorrhage, Hypertensive, mesenchymal stromal cells