Intraarterial transplantation of human umbilical cord blood mononuclear cells is more efficacious and safer compared with umbilical cord mesenchymal stromal cells in a rodent stroke model

被引:50
作者
Karlupia, Neha [1 ,2 ,3 ]
Manley, Nathan C. [1 ,2 ]
Prasad, Kameshwar [3 ]
Schaefer, Richard [1 ]
Steinberg, Gary K. [1 ,2 ]
机构
[1] Stanford Univ, Stanford Sch Med, Dept Neurosurg, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Stanford Stroke Ctr, Stanford, CA 94305 USA
[3] All India Inst Med Sci, Dept Neurol, New Delhi 110029, India
关键词
CEREBRAL-ARTERY OCCLUSION; MULTIPOTENT STEM-CELLS; NITRIC-OXIDE SYNTHASE; REGULATORY T-CELLS; BONE-MARROW; NEUROTROPHIC FACTOR; FLOW-CYTOMETRY; PROGENITOR CELLS; RAT MODEL; STEM/PROGENITOR CELLS;
D O I
10.1186/scrt434
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Introduction: Stroke is the second leading cause of death worldwide, claims six lives every 60 seconds, and is a leading cause of adult disability across the globe. Tissue plasminogen activator, the only United States Food and Drug Administration (FDA)-approved drug currently available, has a narrow therapeutic time window of less than 5 hours. In the past decade, cells derived from the human umbilical cord (HUC) have emerged as a potential therapeutic alternative for stroke; however, the most effective HUC-derived cell population remains unknown. Methods: We compared three cell populations derived from the human umbilical cord: cord blood mononuclear cells (cbMNCs); cord blood mesenchymal stromal cells (cbMSCs), a subpopulation of cbMNCs; and cord matrix MSCs (cmMSCs). We characterized these cells in vitro with flow cytometry and assessed the cells' in vivo efficacy in a 2-hour transient middle cerebral artery occlusion (MCAo) rat model of stroke. cbMNCs, cbMSCs, and cmMSCs were each transplanted intraarterially at 24 hours after stroke. Results: A reduction in neurologic deficit and infarct area was observed in all three cell groups; however, this reduction was significantly enhanced in the cbMNC group compared with the cmMSC group. At 2 weeks after stroke, human nuclei-positive cells were present in the ischemic hemispheres of immunocompetent stroke rats in all three cell groups. Significantly decreased expression of rat brain-derived neurotrophic factor mRNA was observed in the ischemic hemispheres of all three cell-treated and phosphate-buffered saline (PBS) group animals compared with sham animals, although the decrease was least in cbMNC-treated animals. Significantly decreased expression of rat interleukin (IL)-2 mRNA and IL-6 mRNA was seen only in the cbMSC group. Notably, more severe complications (death, eye inflammation) were observed in the cmMSC group compared with the cbMNC and cbMSC groups. Conclusions: All three tested cell types promoted recovery after stroke, but cbMNCs showed enhanced recovery and fewer complications compared with cmMSCs.
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页数:19
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