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Cell Med. 2016 Dec 21;9(3):73-85. doi: 10.3727/215517916X693384. eCollection 2017.

Neurovascular Cell Sheet Transplantation in a Canine Model of Intracranial Hemorrhage.

Lee WJ1,2, Lee JY3, Jung KH1,2, Lee ST1,2, Kim HY4, Park DK2, Yu JS2, Kim SY2, Jeon D2, Kim M2,3, Lee SK1,2, Roh JK1,2,5, Chu K1,2.

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Department of Neurology, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, South Korea.
†Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
‡Department of Neurosurgery, Kangdong Sacred Heart Hospital, Seoul, South Korea.
§Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
¶Department of Neurology, The Armed Forces Capital Hospital, Gyeunggido, South Korea.


Cell-based therapy for intracerebral hemorrhage (ICH) has a great therapeutic potential. However, methods to effectively induce direct regeneration of the damaged neural tissue after cell transplantation have not been established, which, if done, would improve the efficacy of cell-based therapy. In this study, we aimed to develop a cell sheet with neurovasculogenic potential and evaluate its usefulness in a canine ICH model. We designed a composite cell sheet made of neural progenitors derived from human olfactory neuroepithelium and vascular progenitors from human adipose tissue-derived stromal cells. We also generated a physiologic canine ICH model by manually injecting and then infusing autologous blood under arterial pressure. We transplanted the sheet cells (cell sheet group) or saline (control group) at the cortex over the hematoma at subacute stages (2 weeks from ICH induction). At 4 weeks from the cell transplantation, cell survival, migration, and differentiation were evaluated. Hemispheric atrophy and neurobehavioral recovery were also compared between the groups. As a result, the cell sheet was rich in extracellular matrices and expressed neurotrophic factors as well as the markers for neuronal development. After transplantation, the cells successfully survived for 4 weeks, and a large portion of those migrated to the perihematomal site and differentiated into neurons and pericytes (20% and 30% of migrated stem cells, respectively). Transplantation of cell sheets alleviated hemorrhage-related hemispheric atrophy (p = 0.042) and showed tendency for improving functional recovery (p = 0.062). Therefore, we concluded that the cell sheet transplantation technique might induce direct regeneration of neural tissue and might improve outcomes of intracerebral hemorrhage.


Cell sheet; Cell therapy; Intracerebral hemorrhage (ICH); Neurovascular progenitor; Transplantation

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