Neurovascular Cell Sheet Transplantation in a Canine Model of Intracranial Hemorrhage

Cell Medicine

Hyo Yeol Kim¹  Dong-Kyu Park²  So-Yun Kim²  Daejong Jeon²  Jung-Suk Yu²  Manho Kim³  Jong Young Lee⁴  Kon Chu⁵  Sang Kun Lee⁵  Woo-Jin Lee⁵  Soon-Tae Lee⁵  Keun-Hwa Jung⁵  Jae-Kyu Roh⁶ 

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

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

DOI  :  10.3727/215517916X693384

学科分类：生物科学（综合）

来源: Cognizant Communication Corporation

【 摘 要 】

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.

【 授权许可】

CC BY