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Application of bone marrow stem cell biology in the treatment of acute renal failure.

机译：骨髓干细胞生物学在急性肾衰竭治疗中的应用。

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摘要

The physiology of an organ is critically affected in disease states and return to normal function can be accomplished only through restitution of the underlying organ physiology. While many organs possess remarkable capacities of restitution, some injuries are too severe and make this mechanism inefficient. Pharmacological approaches target only a certain aspect of the pathophysiology of a disease and many diseases are multifactorial so that these pharmacological approaches appear insufficient. These insufficiencies of pharmacotherapy can possibly be overcome by using cell therapeutic approaches that all enable targeting multiple causes of one particular complex disease, e.g., inflammatory and ischemic injuries with the same therapeutic agent.; Stem cells are ideal vehicles for cell therapy because of their undifferentiated state and thereby resulting versatility to react to different pathophysiological conditions. Bone marrow (BM) derived stem cells are easily accessible in the autologous and allogeneic setting and their biology has been studied for more than 50 years, making them the most well-characterized adult stem cell population so far.; Acute renal failure (ARF) is a multifactorial syndrome associated with high clinical mortality and disease-specific therapeutic concepts beyond supportive therapy are currently not available. There are several important pathophysiological components of ARF: endothelial damage with subsequently impaired blood flow, inflammation and tubular cell death by apoptosis and necrosis, all contributing to a fall in the glomerular filtration fraction (GFR).; Due to this complex pattern of dysfunction during ARF we hypothesized that bone marrow derived stem cells might be a promising new treatment approach for ARF.; We found that hematopoietic stem cell mobilization by currently applied clinical protocols did not improve but actually worsened ischemia/reperfusion injury by concomitant granulocytosis. Signals involved in mobilization and homing of bone marrow derived cells include the chemokine Stromal cell-derived factor-1 (SDF-1), a so far unrecognized mediator of homing and migration of CXCR4 expressing cells in the injured kidney.; Mesenchymal stem cells from the bone marrow, when administered after ischemic injury, have robust renoprotective potential and enhance recovery from injury by differentiation independent mechanisms including growth factor secretion, vascular support and immunomodulation.; Our studies demonstrate the promising potential of BM derived stem cells for cell therapeutic approaches in ARF.
机译：在疾病状态下，器官的生理受到严重影响，只有通过恢复潜在的器官生理才能恢复正常功能。尽管许多器官具有非凡的赔偿能力，但某些伤害太重，使该机制效率低下。药理学方法仅针对疾病的病理生理学的某个方面，并且许多疾病是多因素的，因此这些药理学方法似乎不足。可以通过使用细胞治疗方法来克服药物治疗的这些不足，这些方法都能够针对一种特定的复杂疾病的多种原因，例如使用相同的治疗剂引起炎性和缺血性损伤。干细胞由于其未分化状态，因此具有对多种病理生理条件做出反应的多功能性，因此是用于细胞治疗的理想载体。骨髓（BM）衍生的干细胞在自体和同种异体环境中很容易获得，其生物学已经研究了50多年，使它们成为迄今最具特征的成年干细胞群体。急性肾衰竭（ARF）是一种与高临床死亡率相关的多因素综合征，目前尚无支持疗法以外的疾病特异性治疗概念。 ARF有几个重要的病理生理组成部分：内皮损伤，随后受损的血流，炎症和由凋亡和坏死引起的肾小管细胞死亡，所有这些都导致肾小球滤过率（GFR）下降。由于ARF期间功能障碍的这种复杂模式，我们假设骨髓衍生干细胞可能是ARF的一种有前途的新治疗方法。我们发现，当前应用的临床方案对造血干细胞的动员并没有改善，但实际上伴随着粒细胞增多而使局部缺血/再灌注损伤加重。涉及动员和归巢骨髓衍生细胞的信号包括趋化因子基质细胞衍生因子1（SDF-1），这是迄今为止尚无法识别的CXCR4表达细胞在受损肾脏中归巢和迁移的介质。缺血损伤后给予的骨髓间充质干细胞具有强大的肾脏保护潜力，并通过包括生长因子分泌，血管支持和免疫调节在内的分化独立机制增强了从损伤中恢复的能力。我们的研究证明了BM衍生干细胞在ARF中用于细胞治疗的潜力。

著录项

  • 作者

    Togel, Florian Erhard.;

  • 作者单位

    The University of Utah.;

  • 授予单位 The University of Utah.;
  • 学科 Health Sciences Medicine and Surgery.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 67 p.
  • 总页数 67
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 R501;R601;
  • 关键词

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