THERAPEUTIC USE OF STEM CELLS

干细胞的治疗用途

• 批准号: 6269758
• 负责人: RICHARD J JONES
• 金额: $ 21.9万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-30 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6269758
• 关键词: CD34 molecule; aplastic anemia; artificial immunosuppression; autoimmune disorder; autologous transplantation; bone marrow purging; bone marrow transplantation; clinical research; cyclophosphamide; dyserythropoietic anemia; embryo /fetus surgery; fluorescent in situ hybridization; genetic disorder; hematopoiesis; hematopoietic stem cells; homologous transplantation; human pregnant subject; human subject; human therapy evaluation; immunosuppressive; 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.

分离和扩增淋巴造血干细胞 (HSC) 的能力 应提高临床骨髓的可用性和结果 移植（BMT）。此外，HSC 的临床移植 目前唯一能明确证明人类 HSC 的方法 孤立。尽管 BMT 是大多数血液病的治疗方法 恶性肿瘤和各种​​致命的非恶性疾病 影响淋巴造血系统，大多数患者患有这些 疾病仍未治愈。这在很大程度上是因为患者 患有这些疾病的人要么不符合 BMT 条件，要么无法接受 BMT。移植物 含有HSC也应该是消除（清除）的重要方法 来自自体骨髓移植的肿瘤，尤其是慢性粒细胞白血病等疾病 和骨髓增生异常综合征（MDS），难以根除肿瘤，同时 产生正常的造血作用。纯化同种异体 HSC 移植 应该是避免组织相容性问题的重要策略， 移植物抗宿主病（GVHD）和移植排斥，与 同种异体骨髓移植。纯化的 HSC 也可能是有效基因所必需的 淋巴造血细胞的转移疗法，因为这些细胞很稀有 细胞可能使它们无法使用目前的基因转移技术 这些技术可能会优先影响增殖更快的 承诺的祖先。该项目的总体目标是研究 使用 HSC 治疗多种疾病。我们将研究 使用自体 HSC 治疗 MDS 等干细胞衰竭疾病， 严重再生障碍性贫血 (SAA) 和阵发性睡眠性血红蛋白尿 (PNH)。我们的初步数据表明，大多数患者的缺陷 再生障碍性贫血和MDS是在骨髓干细胞水平而不是 最早的HSC；此外，许多患有再生障碍性贫血和MDS的患者 最早的 HSC 数量相对正常。我们也会学习 自体 HSC 用于治疗难治性、危及生命的患者 自身免疫性疾病，如狼疮。最后，我们将利用隔离 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；具体来说，我们将在子宫内进行调查 同种异体造血干细胞移植治疗遗传性疾病。