THERAPEUTIC USE OF STEM CELLS

干细胞的治疗用途

• 批准号: 6579391
• 负责人: RICHARD J JONES
• 金额: $ 22.86万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-24 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6579391
• 关键词: CD34 molecule; aplastic anemia; artificial immunosuppression; autoimmune disorder; autologous transplantation; bone marrow purging; bone marrow transplantation; clinical research; cyclophosphamide; dyserythropoietic anemia; fluorescent in situ hybridization; genetic disorder; hematopoiesis; hematopoietic stem cells; homologous transplantation; human pregnant subject; human subject; human therapy evaluation; immunosuppressive; in utero transplantation; paroxysmal nocturnal hemoglobinuria; pediatric neoplasm /cancer; systemic lupus erythematosus

The ability to isolate and expand lymphohematopoietic stem cells (HSC) should improve both the availability and outcome of clinical bone marrow transplantation (BMT). Moreover, clinical transplants with HSC are currently the only way to definitively prove that human HSC have been isolated. Although BMT is curative therapy for most hematologic malignancies and for a variety of fatal non-malignant disorders that effect the lymphohematopoietic system, the majority of patients with these diseases are still not cured. This is, in large part, because patients with these diseases either are not eligible for, or fail, BMT. A graft containing HSC should also be an important method of eliminating (purging) tumor from autologous marrow grafts, especially in those diseases like CML and MDS where it has been difficult to eradicate tumor and simultaneously generate normal hematopoiesis. Transplantation of purified allogeneic HSC should be an important strategy for avoiding histocompatibility problems, graft-versus-host disease (GVHD) and graft rejection, associated with allogeneic BMT. Purified HSC may also be necessary for effective gene transfer therapy for lymphohematopoietic cells, as the rarity of these cells may make them inaccessible to present gene transfer techniques and these techniques may preferentially affect the more rapidly proliferating committed progenitors. The overall objective of this project is to study the use of HSC as treatment for a variety of disease. We will study the use of autologous HSC as treatment of stem failure disorders like MDS, severe aplastic anemia (SAA), and paroxysmal nocturnal hemoglobinuria (PNH). Our preliminary data suggest that the defect in most patients with aplastic anemia and MDS is at the level of a myeloid stem cell rather than the earliest HSC; further, many patients with aplastic anemia and MDS have relatively normal numbers of the earliest HSC. We will also study autologous HSC in the treatment for refractory, life-threatening autoimmune diseases like lupus. Finally, we will utilize isolated allogeneic HSC as a means to overcome histocompatibility problems associated with allogeneic BMT; specifically we will investigate in utero transplantation with allogeneic HSC to treat genetic diseases.

分离和膨胀淋巴瘤干细胞的能力（HSC） 应该改善临床骨髓的可用性和结果 移植（BMT）。此外，使用HSC的临床移植是 目前，明确证明人类HSC的唯一方法已经 孤立。尽管BMT是大多数血液学的治疗疗法 恶性肿瘤和各种​​致命的非恶性疾病 影响淋巴瘤系统，大多数患者 疾病仍未治愈。这在很大程度上是因为患者 对于这些疾病，要么不符合BMT的资格或失败。嫁接 含有HSC也应该是消除（清除）的重要方法 自体骨髓移植物的肿瘤，尤其是在CML等疾病中 和MD难以消除肿瘤并同时消除肿瘤 产生正常的造血。纯化的同种异体HSC的移植 应该是避免组织相容性问题的重要策略， 移植物与宿主病（GVHD）和移植物排斥相关 同种异体BMT。有效基因也可能需要纯化的HSC 淋巴瘤细胞的转移疗法，因为这些细胞的稀有性 细胞可能使它们无法访问基因转移技术，并且 这些技术可能优先影响更快的增殖 坚定的祖细胞。该项目的总体目的是研究 将HSC用作多种疾病的治疗方法。我们将研究 使用自体HSC作为MD等茎衰竭障碍的治疗， 严重的相位贫血（SAA）和阵发性夜间血红蛋白尿症 （PNH）。我们的初步数据表明，大多数患者的缺陷 性贫血和MD处于髓样干细胞的水平，而不是 最早的HSC；此外，许多患有性贫血和MD的患者患有 最早的HSC的相对正常数。我们还将学习 自体HSC治疗难治性，威胁生命 狼疮等自身免疫性疾病。最后，我们将利用孤立的 同种异体HSC作为克服组织相容性问题的一种手段 与同种异体BMT相关；具体而言，我们将在子宫里进行调查 用同种异体HSC移植以治疗遗传疾病。