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別タイトル
微少重力環境は脊髄損傷における骨髄間質細胞移植において細胞の遊走と神経保護を促進する
著者
光原 崇文
キーワード
Bone marrow stromal cell
Migration
Simulated microgravity
Spinal cord injury
Survival
Trophic factor
NDC
医学
抄録(英)
Introduction: Recently, cell-based therapy has gained significant attention for the treatment of central nervous system diseases. Although bone marrow stromal cells (BMSCs) are considered to have good engraftment potential, challenges due to in vitro culturing, such as a decline in their functional potency, have been reported. Here, we investigated the efficacy of rat BMSCs (rBMSCs) cultured under simulated microgravity conditions, for transplantation into a rat model of spinal cord injury (SCI).

Methods: rBMSCs were cultured under two different conditions: standard gravity (1G) and simulated microgravity attained by using the 3D-clinostat. After 7 days of culture, the rBMSCs were analyzed morphologically, with RT-PCR and immunostaining, and were used for grafting. Adult rats were used for constructing SCI models by using a weight-dropping method and were grouped into three experimental groups for comparison. rBMSCs cultured under 1 g and simulated microgravity were transplanted intravenously immediately after SCI. We evaluated the hindlimb functional improvement for 3 weeks. Tissue repair after SCI was examined by calculating the cavity area ratio and immunohistochemistry.

Results: rBMSCs cultured under simulated microgravity expressed Oct-4 and CXCR4, in contrast to those cultured under 1 g conditions. Therefore, rBMSCs cultured under simulated microgravity were considered to be in an undifferentiated state and thus to possess high migration ability. After transplantation, grafted rBMSCs cultured under microgravity exhibited greater survival at the periphery of the lesion, and the motor functions of the rats that received these grafts improved significantly compared with the rats that received rBMSCs cultured in 1 g. In addition, rBMSCs cultured under microgravity were thought to have greater trophic effects on reestablishment and survival of host spinal neural tissues because cavity formations were reduced, and apoptosis-inhibiting factor expression was high at the periphery of the SCI lesion.

Conclusions: Here we show that transplantation of rBMSCs cultured under simulated microgravity facilitates functional recovery from SCI rather than those cultured under 1 g conditions.
作成年月日
2014-11-21
言語
英語
NII資源タイプ
学位論文
広大資料タイプ
学位論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
ETD
権利情報
Copyright(c) by Author
関連情報(references)
Takafumi Mitsuhara, Masaaki Takeda, Satoshi Yamaguchi, Tomotaka Manabe, Masaya Matsumoto, Yumi Kawahara, Louis Yuge and Kaoru Kurisu; Simulated microgravity facilitates cell migration and neuroprotection after bone marrow stromal cell transplantation in spinal cord injury; Stem Cell Research & Therapy 2013, Volume 4 Issue 2 (doi: 10.1186/scrt184)
関連情報URL(references)
http://stemcellres.com/content/4/2/35
学位記番号
甲第6200号
授与大学
広島大学(Hiroshima University)
学位名
博士(医学)
学位名の英名
Philosophy in Medical Science
学位の種類の英名
doctoral
学位授与年月日
2013-05-23
部局名
医歯薬学総合研究科