Burt Richard K, Loh Yvonne, Pearce William, Beohar Nirat, Barr Walter G, Craig Robert, Wen Yanting, Rapp Jonathan A, Kessler John
Division of Immunotherapy, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
JAMA. 2008 Feb 27;299(8):925-36. doi: 10.1001/jama.299.8.925.
Stem cell therapy is rapidly developing and has generated excitement and promise as well as confusion and at times contradictory results in the lay and scientific literature. Many types of stem cells show great promise, but clinical application has lagged due to ethical concerns or difficulties in harvesting or safely and efficiently expanding sufficient quantities. In contrast, clinical indications for blood-derived (from peripheral or umbilical cord blood) and bone marrow-derived stem cells, which can be easily and safely harvested, are rapidly increasing.
To summarize new, nonmalignant, nonhematologic clinical indications for use of blood- and bone marrow-derived stem cells.
Search of multiple electronic databases (MEDLINE, EMBASE, Science Citation Index), US Food and Drug Administration [FDA] Drug Site, and National Institutes of Health Web site to identify studies published from January 1997 to December 2007 on use of hematopoietic stem cells (HSCs) in autoimmune, cardiac, or vascular diseases. The search was augmented by hand searching of reference lists in clinical trials, review articles, proceedings booklets, FDA reports, and contact with study authors and device and pharmaceutical companies.
Of 926 reports identified, 323 were examined for feasibility and toxicity, including those with small numbers of patients, interim or substudy reports, and reports on multiple diseases, treatment of relapse, toxicity, mechanism of action, or stem cell mobilization. Another 69 were evaluated for outcomes. For autoimmune diseases, 26 reports representing 854 patients reported treatment-related mortality of less than 1% (2/220 patients) for nonmyeloablative, less than 2% (3/197) for dose-reduced myeloablative, and 13% (13/100) for intense myeloablative regimens, ie, those including total body irradiation or high-dose busulfan. While all trials performed during the inflammatory stage of autoimmune disease suggested that transplantation of HSCs may have a potent disease-remitting effect, remission duration remains unclear, and no randomized trials have been published. For reports involving cardiovascular diseases, including 17 reports involving 1002 patients with acute myocardial infarction, 16 involving 493 patients with chronic coronary artery disease, and 3 meta-analyses, the evidence suggests that stem cell transplantation performed in patients with coronary artery disease may contribute to modest improvement in cardiac function.
Stem cells harvested from blood or marrow, whether administered as purified HSCs or mesenchymal stem cells or as an unmanipulated or unpurified product can, under appropriate conditions in select patients, provide disease-ameliorating effects in some autoimmune diseases and cardiovascular disorders. Clinical trials are needed to determine the most appropriate cell type, dose, method, timing of delivery, and adverse effects of adult HSCs for these and other nonmalignant disorders.
干细胞疗法正在迅速发展，在大众和科学文献中引发了兴奋与希望，同时也带来了困惑，有时还出现相互矛盾的结果。许多类型的干细胞显示出巨大的前景，但由于伦理问题、采集困难或难以安全有效地扩增足够数量的细胞，其临床应用一直滞后。相比之下，血液来源（外周血或脐带血）和骨髓来源的干细胞，因其可轻松、安全地采集，其临床应用指征正在迅速增加。
总结血液和骨髓来源干细胞用于非恶性、非血液学疾病的新的临床指征。
检索多个电子数据库（MEDLINE、EMBASE、科学引文索引）、美国食品药品监督管理局（FDA）药品网站以及国立卫生研究院网站，以识别1997年1月至2007年12月期间发表的关于造血干细胞（HSCs）用于自身免疫性疾病、心脏疾病或血管疾病的研究。通过手工检索临床试验、综述文章、会议论文集、FDA报告中的参考文献列表，并与研究作者以及器械和制药公司联系，对检索结果进行补充。
在识别出的926篇报告中，对323篇报告进行了可行性和毒性检查，包括患者数量较少的报告、中期或子研究报告，以及关于多种疾病、复发治疗、毒性、作用机制或干细胞动员的报告。另外69篇报告进行了结果评估。对于自身免疫性疾病，26篇报告涉及854例患者，结果显示非清髓性方案的治疗相关死亡率低于1%（220例患者中有2例），剂量降低的清髓性方案低于2%（197例患者中有3例），强化清髓性方案（即包括全身照射或高剂量白消安的方案）为13%（100例患者中有13例）。虽然在自身免疫性疾病炎症阶段进行的所有试验都表明，造血干细胞移植可能具有强大的疾病缓解作用，但缓解持续时间尚不清楚，且尚未发表随机试验报告。对于涉及心血管疾病的报告，包括17篇涉及1002例急性心肌梗死患者的报告、16篇涉及493例慢性冠状动脉疾病患者的报告以及3篇荟萃分析，证据表明在冠状动脉疾病患者中进行干细胞移植可能有助于适度改善心脏功能。
从血液或骨髓中采集的干细胞，无论是作为纯化的造血干细胞或间充质干细胞给药，还是作为未处理或未纯化的产品给药，在特定患者的适当条件下，都可以在某些自身免疫性疾病和心血管疾病中产生改善疾病的效果。需要进行临床试验，以确定用于这些及其他非恶性疾病的最合适的细胞类型、剂量、方法、给药时间以及成人造血干细胞的不良反应。
