Control of the HSC Niche Signaling for the Efficient Long-Term Engraftment of Hematopoietic Stem Cells without Irradiation or High-Dose Chemotherapy

控制 HSC 生态位信号传导，实现造血干细胞的有效长期植入，无需辐射或高剂量化疗

• 批准号: 21791003
• 负责人: YOSHIHARA Hiroki
• 金额: $ 2.75万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791003/
• 关键词: 移植・再生医療; プロテオーム

Irradiation and high-dose chemotherapy followed by bone marrow transplantation (BMT) have been a routine treatment for hematological malignancies and solid tumors. These conditioning, however, should be minimized since the toxicity extends to all organs generating serious side effects. In the adult BM, HSCs interact with its microenvironment which supports the activity of HSCs to maintain quiescence or self-renew to provide blood cells throughout the lifetime of an individual. This particular microenvironment, called stem cell niche, is critical for the maintenance of HSCs. In this study, we manipulated the niche for efficient engraftment avoiding redundant side effects of conditionings. We found that AMM2 or interferon-alpha is a promising niche regulator for transplantation without irradiation or high dose chemotherapy. Achievement of non-irradiated BMT method will provide advancement in stem cell therapy overcoming serious side effects.

放疗和大剂量化疗后进行骨髓移植（BMT）已成为恶性血液病和实体瘤的常规治疗方法。然而，这些条件应尽量减少，因为毒性扩展到所有器官，产生严重的副作用。在成年BM中，HSC与其微环境相互作用，微环境支持HSC的活性以维持静止或自我更新，从而在个体的整个生命周期中提供血细胞。这种特殊的微环境，称为干细胞生态位，对于维持HSC至关重要。在这项研究中，我们操纵的利基有效的植入避免多余的副作用的条件。我们发现，AMM 2或干扰素-α是一个有前途的小生境调节移植没有辐射或高剂量化疗。非辐射骨髓移植方法的实现将为克服严重的副作用提供干细胞治疗的进展。

项目成果

Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells

• DOI: 10.1182/blood-2009-05-224857
• 发表时间: 2010-07-29
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Hosokawa, Kentaro;Arai, Fumio;Suda, Toshio
• 通讯作者: Suda, Toshio

Niche regulation of hematopoietic stem cells in the endosteum.

内膜造血干细胞的生态位调节。

• 发表时间: 2009
• 期刊: Ann N Y Acad Sci 1176
• 作者: Arai F;Yoshihara H;Hosokawa K;Nakamura Y;Gomei Y;Iwasaki H;Suda T.
• 通讯作者: Suda T.

Cadherin-Based Adhesion Is a Potential Target for Niche Manipulation to Protect Hematopoietic Stem Cells in Adult Bone Marrow

• DOI: 10.1016/j.stem.2009.04.013
• 发表时间: 2010-03-05
• 期刊: CELL STEM CELL
• 影响因子: 23.9
• 作者: Hosokawa, Kentaro;Arai, Fumio;Suda, Toshio
• 通讯作者: Suda, Toshio

リン酸化タンパク質の網羅的解析

磷酸化蛋白质的综合分析

• 发表时间: 2010
• 期刊: 病理と臨床 28(5)
• 作者: 吉原宏樹;石濱泰
• 通讯作者: 石濱泰

Phosphoproteomic Profiling of Leukemia Cells

白血病细胞的磷酸化蛋白质组学分析

• 发表时间: 2010
• 作者: Sato T;Onai N;Yoshihara H;Arai F;Suda T;Ohteki T.;吉原宏樹
• 通讯作者: 吉原宏樹