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心力衰竭的细胞治疗——肌肉、骨髓、血液及心脏来源的干细胞

Cell therapy for heart failure--muscle, bone marrow, blood, and cardiac-derived stem cells.

作者信息

Ott Harald C, Davis Bryce H, Taylor Doris A

机构信息

Center for Cardiovascular Repair, University of Minnesota, Minneapolis, Minnesota 55455, USA.

出版信息

Semin Thorac Cardiovasc Surg. 2005 Winter;17(4):348-60. doi: 10.1053/j.semtcvs.2005.09.004.

Abstract

Heart failure (HF) affects a rapidly growing population of patients. Despite improvements in the understanding and therapy of many stages of cardiovascular disease, there has been little progress in treating HF. In the late-stage disease, current options are cardiac transplantation and mechanical support--options that are limited to a small patient collective. The ischemically injured failing heart lacks contractile myocardium, functional vasculature, and electrical integrity, which has made treatment of the underlying injury untenable in the past. Restoring all of these components seems an overwhelming challenge. Yet, the concept of cell therapy--tissue repair by transplantation of stem and progenitor cells--has opened new potential options for patients with heart failure. Skeletal myoblasts, bone marrow, and blood-derived stem cells have all shown considerable myogenic and angiogenic potential in vitro and have rapidly moved from bench to bedside. A number of nonrandomized, non-placebo-controlled safety and feasibility studies have been reported and now double-blinded randomized controlled trials are underway. Despite this rapid clinical pace, the exact mechanisms underlying the functional benefits of different cell types are not well understood. Instead, multiple similar mechanism have been ascribed to virtually every cell type. Thus, while the field is exciting and offers unheralded promise to treat patients with CVD, we must proceed with due diligence and caution. Only a deep understanding of the benefits versus the risks, and the mechanisms involved in cell-mediated cardiac repair, will allow us to design clinically valuable tools and fulfill the potential of this exciting 21st century approach to treating cardiovascular disease.

摘要

心力衰竭(HF)影响着数量迅速增长的患者群体。尽管在心血管疾病多个阶段的认识和治疗方面有所改善,但在治疗HF方面进展甚微。在疾病晚期,目前的选择是心脏移植和机械支持——这些选择仅限于一小部分患者群体。缺血性损伤的衰竭心脏缺乏收缩性心肌、功能性脉管系统和电完整性,这使得过去对潜在损伤的治疗难以实现。恢复所有这些成分似乎是一项艰巨的挑战。然而,细胞治疗的概念——通过移植干细胞和祖细胞进行组织修复——为心力衰竭患者开辟了新的潜在选择。骨骼肌成肌细胞、骨髓和血液来源的干细胞在体外均显示出相当大的成肌和血管生成潜力,并迅速从实验室走向临床。已经报道了一些非随机、非安慰剂对照的安全性和可行性研究,现在双盲随机对照试验正在进行。尽管临床进展迅速,但不同细胞类型功能益处背后的确切机制尚未完全了解。相反,几乎每种细胞类型都被归因于多种相似的机制。因此,虽然这个领域令人兴奋,并为治疗心血管疾病患者带来了前所未有的希望,但我们必须谨慎行事。只有深入了解益处与风险以及细胞介导的心脏修复所涉及的机制,才能使我们设计出具有临床价值的工具,并实现这种令人兴奋的21世纪心血管疾病治疗方法的潜力。

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