日本小児循環器学会雑誌 Pediatric Cardiology and Cardiac Surgery

Online ISSN: 2187-2988 Print ISSN: 0911-1794
特定非営利活動法人日本小児循環器学会 Japanese Society of Pediatric Cardiology and Cardiac Surgery
〒162-0801東京都新宿区山吹町358-5アカデミーセンター Japanese Society of Pediatric Cardiology and Cardiac Surgery Academy Center, 358-5 Yamabuki-cho, Shinju-ku, Tokyo 162-0801, Japan
Pediatric Cardiology and Cardiac Surgery 31(3): 80-87 (2015)
doi:10.9794/jspccs.31.80

ReviewReview

CD34陽性細胞移植による血管・組織の再生治療Vascular and Tissue Regeneration by CD34+ Cells

1公益財団法人先端医療振興財団先端医療センター病院診療部再生治療ユニットUnit of Regenerative Medicine, Institute of Biomedical Research and Innovation Hospital, Foundation for Biomedical Research and Innovation ◇ 〒650-0047 兵庫県神戸市中央区港島南町二丁目2番2-2 Minatojima-Minami-machi, Chuo-ku, Kobe-shi, Hyogo 650-0047, Japan

2公益財団法人先端医療振興財団先端医療センター研究所再生医療研究部血管再生研究グループRevascular Regeneration Research Group, Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation Laboratory, Foundation for Biomedical Research and Innovation ◇ 〒650-0047 兵庫県神戸市中央区港島南町二丁目2番2-2 Minatojima-Minami-machi, Chuo-ku, Kobe-shi, Hyogo 650-0047, Japan

受付日:2014年11月14日Received: November 14, 2014
受理日:2015年1月16日Accepted: January 16, 2015
発行日:2015年5月1日Published: May 1, 2015
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CD34は様々な体性幹細胞の表面マーカであり,骨髄由来の造血幹細胞/血管内皮前駆細胞,骨格筋衛星細胞,毛包幹細胞,脂肪組織間葉系幹細胞などに発現している.骨髄または顆粒球コロニー刺激因子(granulocyte colony stimulating factor: GCSF)動員CD34陽性細胞を用いた血管再生療法は,慢性重症下肢虚血,治療抵抗性狭心症,急性心筋梗塞,拡張型心筋症など様々な心血管疾患患者を対象に開始され,高い安全性と良好な初期成績が報告されている.当研究グループでは,慢性重症下肢虚血患者に対する第I/II相,第II相臨床試験を終え,現在第III相試験の準備中である.最近では,心血管疾患以外に,肝硬変や難治性骨折など,その病態に局所の血流障害が関与する疾病に対しても,GCSF動員CD34陽性細胞移植治療が行われ,良好な初期成績が示されている.

本総説では,骨髄由来CD34陽性細胞を用いた血管再生治療について,前臨床試験および初期臨床試験の成績を紹介し,将来の展望についても言及する.

CD34 is a cell surface marker, which is expressed in various somatic stem/progenitor cells such as bone marrow (BM)-derived hematopoietic stem cells and endothelial progenitor cells (EPCs), skeletal muscle satellite cells, epithelial hair follicle stem cells, and adipose tissue mesenchymal stem cells. CD34+ cells in BM and peripheral blood are known as a rich source of EPCs; therefore, therapeutic application of BM-derived CD34+ cells has been attempted for vascular regeneration in cardiovascular diseases. Preclinical and early clinical studies of BM or granulocyte colony-stimulating factor (GCSF)-mobilized CD34+ cell therapy revealed promising outcomes with regard to safety, feasibility, and potential efficacy in critical limb ischemia (CLI) by atherosclerosis obliterans or Buerger’s disease, acute myocardial infarction, chronic myocardial ischemia (refractory angina), and dilated cardiomyopathy. Our research group is now preparing for a phase III clinical trial of CD34+ cell therapy in CLI on the basis of previous phase I/II and phase II trials.

Recently, CD34+ cell therapy has also been applied to non-healing fractures and decompensated liver cirrhosis, in which reduced blood supply is a key factor associated with disease progression. Both preclinical and pilot clinical investigations indicated the safety, feasibility, and effectiveness of GCSF-mobilized CD34+ cell therapy in these non-cardiovascular diseases. This review provides an overview of the preclinical and clinical reports to demonstrate the usefulness, current limitations, and future prospects of cell-based therapy in various types of diseases.

Key words: CD34; cell therapy; clinical trial; ischemia; regeneration

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