Transplantation of human neural stem/progenitor cells overexpressing galectin-1 improves functional recovery from focal brain ischemia in the mongolian gerbil

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作者
Junichi Yamane
Satoru Ishibashi
Masanori Sakaguchi
Toshihiko Kuroiwa
Yonehiro Kanemura
Masaya Nakamura
Hiroyuki Miyoshi
Kazunobu Sawamoto
Yoshiaki Toyama
Hidehiro Mizusawa
Hideyuki Okano
机构
[1] Keio University School of Medicine,Department of Physiology
[2] Keio University School of Medicine,Department of Orthopaedic Surgery
[3] Tokyo Dental College Ichikawa General Hospital,Department of Orthopaedic Surgery
[4] Graduate School of Medicine,Department of Neurology and Neurological Science
[5] Tokyo Medical and Dental University,Department of Clinical Laboratory
[6] Namegata District General Hospital,Division of Regenerative Medicine
[7] Institute for Clinical Research,Department of Neurosurgery
[8] Osaka National Hospital,Subteam for Manipulation of Cell Fate
[9] National Hospital Organization,Bridgestone Laboratory of Developmental and Regenerative Neurobiology
[10] Osaka National Hospital,Department of Developmental and Regenerative Biology
[11] National Hospital Organization,undefined
[12] RIKEN BioResource Center,undefined
[13] Keio University School of Medicine,undefined
[14] Nagoya City University Graduate School of Medical Sciences,undefined
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关键词
Neurite Outgrowth; Brain Ischemia; Reactive Astrocyte; Mongolian Gerbil; Ischemic Region;
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摘要
Transplantation of human neural stem/progenitor cells (hNSPCs) is a promising method to regenerate tissue from damage and recover function in various neurological diseases including brain ischemia. Galectin-1(Gal1) is a lectin that is expressed in damaged brain areas after ischemia. Here, we characterized the detailed Gal1 expression pattern in an animal model of brain ischemia. After brain ischemia, Gal1 was expressed in reactive astrocytes within and around the infarcted region, and its expression diminished over time. Previously, we showed that infusion of human Gal1 protein (hGal1) resulted in functional recovery after brain ischemia but failed to reduce the volume of the ischemic region. This prompted us to examine whether the combination of hNSPCs-transplantation and stable delivery of hGal1 around the ischemic region could reduce the ischemic volume and promote better functional recovery after brain ischemia. In this study, we transplanted hNSPCs that stably overexpressed hGal1 (hGal1-hNSPCs) in a model of unilateral focal brain ischemia using Mongolian gerbils. Indeed, we found that transplantation of hGal1-hNSPCs both reduced the ischemic volume and improved deficits in motor function after brain ischemia to a greater extent than the transplantation of hNSPCs alone. This study provides evidence for a potential application of hGal1 with hNSPCs-transplantation in the treatment of brain ischemia.
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