Intraarterial transplantation of human umbilical cord blood mononuclear cells in hyperacute stroke improves vascular function

• Published in: Stem cell research & therapy Vol. 8; no. 1; p. 74
• Main Authors: Huang, Lei, Liu, Yichu, Lu, Jianfei, Cerqueira, Bianca, Misra, Vivek, Duong, Timothy Q
• Format: Journal Article
• Language: English
• Published: England BioMed Central 22.03.2017
• Subjects: Angiogenesis; Animals; Biomarkers - metabolism; Blood flow; Blood Flow Velocity; Bone marrow; Brain Ischemia - metabolism; Brain Ischemia - pathology; Brain Ischemia - therapy; Carbon dioxide; Carotid arteries; Carotid artery; Carotid Artery, Internal; Cell Differentiation; Cell Separation; Cerebral blood flow; Cerebrovascular Circulation; Cerebrovascular system; Cord blood; Cytology; Disease Models, Animal; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Experiments; Feet; Fetal Blood - cytology; Fetal Blood - metabolism; Functional magnetic resonance imaging; Gene Expression; Heart rate; Humans; Injections, Intra-Arterial; Ischemia; Laboratory animals; Leukocytes (mononuclear); Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - transplantation; Male; Microvasculature; NMR; Nuclear magnetic resonance; Perfusion; Physiology; Postural Balance - physiology; Rats; Rats, Sprague-Dawley; Reperfusion; Rodents; Stem cell transplantation; Stem cells; Stroke; Stroke - metabolism; Stroke - pathology; Stroke - therapy; Transplantation; Transplantation, Heterologous; Umbilical cord; Veins & arteries; Von Willebrand factor; von Willebrand Factor - genetics; von Willebrand Factor - metabolism; Stroke; MRI; CBF; Cell transplantation; Umbilical cord blood cell; Vasoreactivity
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-017-0529-y

Human umbilical cord blood (hUCB) cell therapy is a promising treatment for ischemic stroke. The effects of hyperacute stem cell transplantation on cerebrovascular function in ischemic stroke are, however, not well understood. This study evaluated the effects of hyperacute intraarterial transplantation of hUCB mononuclear cells (MNCs) on cerebrovascular function in stroke rats using serial magnetic resonance imaging (MRI). HUCB MNCs or vehicle were administered to stroke rats via the internal carotid artery immediately after reperfusion at 60 min following ischemia onset. Lesion volumes were longitudinally evaluated by MRI on days 0, 2, 14, and 28 after stroke, accompanied by behavioral tests. Cerebral blood flow (CBF) and cerebrovascular reactivity were measured by perfusion MRI and CO functional MRI (fMRI) at 28 days post-stroke; corresponding vascular morphological changes were also detected by immunohistology in the same animals. We found that CBF to the stroke-affected region at 28 days was improved (normalized CBF value: 1.41 ± 0.30 versus 0.49 ± 0.07) by intraarterial transplantation of hUCB MNCs in the hyperacute stroke phase, compared to vehicle control. Cerebrovascular reactivity within the stroke-affected area, measured by CBF fMRI, was also increased (35.2 ± 3.5% versus 12.8 ± 4.3%), as well as the corresponding cerebrovascular density. Some engrafted cells appeared with microvascular-like morphology and stained positive for von Willebrand Factor (an endothelial cell marker), suggesting they differentiated into endothelial cells. Some engrafted cells also connected to host endothelial cells, suggesting they interacted with the host vasculature. Compared to the vehicle group, infarct volume at 28 days in the stem cell treated group was significantly smaller (160.9 ± 15.7 versus 231.2 ± 16.0 mm ); behavioral deficits were also markedly reduced by stem cell treatment at day 28 (19.5 ± 1.0% versus 30.7 ± 4.7% on the foot fault test; 68.2 ± 4.6% versus 86.6 ± 5.8% on the cylinder test). More tissue within initial perfusion-diffusion mismatch was rescued in the treatment group. Intraarterial hUCB MNC transplantation during the hyperacute phase of ischemic stroke improved cerebrovascular function and reduced behavioral deficits and infarct volume.