Exp Neurobiol.  2017 Feb;26(1):55-65. 10.5607/en.2017.26.1.55.

Effect of Single and Double Administration of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Following Focal Cerebral Ischemia in Rats

Affiliations
  • 1Department of Neurosurgery, Seoul National University College of Medicine, Seoul 03080, Korea. paeksh@snu.ac.kr
  • 2Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
  • 3Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
  • 4Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 13494, Korea.
  • 5Stem Cell & Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea.
  • 6Department of Neurosurgery, Soonchunhyang University Hospital, Seoul 31151, Korea.

Abstract

Stem cell therapies are administered during the acute phase of stroke to preserve the penumbral tissues from ischemic injury. However, the effect of repeated cell therapy during the acute phase remains unclear. In this study, we investigated and compared the functional outcome of single (two days post-injury) and repeated (two and nine days post-injury) treatment with human umbilical cord derived mesenchymal stem cells (hUCB-MSCs) after middle cerebral artery occlusion (MCAO). The rotarod and limb placement tests were utilized to investigate functional outcomes, while infarct volume and tissue damage were measured by immunofluorescent staining for neovascularization, neurogenesis, apoptosis, and inflammation in the penumbral zones. We observed notable motor dysfunction and a significant decrease in infarcted brain volume, as well as increases in neurons and vessels in both single and repeated hUCB-MSC treatments compared to the control group. Interestingly, repeated administration of hUCB-MSCs was not found to elicit additional or synergistic improvements over monotherapy. This study suggests that a clearer understanding of the therapeutic window after stroke will facilitate the development of more efficient treatment protocols in the clinical application of stem cell therapy.

Keyword

Human umbilical cord blood mesenchymal stem cell; Ischemia; repeat therapy; Angiogenesis; Neurogenesis

MeSH Terms

Animals
Apoptosis
Brain
Brain Ischemia*
Cell- and Tissue-Based Therapy
Clinical Protocols
Extremities
Humans*
Infarction, Middle Cerebral Artery
Inflammation
Ischemia
Mesenchymal Stromal Cells*
Neurogenesis
Neurons
Rats*
Stem Cells
Stroke
Umbilical Cord*
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