Humphreys B D, Duffield J D, Bonventre J V
Renal Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Minerva Urol Nefrol. 2006 Mar;58(1):13-21.
The kidney has a dramatic capacity to regenerate after injury. Whether stem cells are the source of the epithelial progenitors replacing injured and dying tubular epithelium is currently an area of intense investigation. Studies from our laboratory and others have supported a model whereby many surviving renal epithelial cells after injury become dedifferentiated and take on mesenchymal characteristics. These cells proliferate to restore the integrity of the denuded basement membrane, and subsequently redifferentiate into a functional epithelium. An alternative possibility is that a minority of surviving intratubular cells possess stem cell properties and selectively proliferate after damage to neighboring cells. Some evidence exists to support this hypothesis but it has not yet been rigorously evaluated. A third hypothesis is that extratubular cells contribute to repair of damaged epithelium. Bone marrow-derived stem cells have been proposed to contribute to this process but our work and work of others indicates that the vast majority of tubular cells derive from an intrarenal source. Recent evidence suggests that interstitial cells may represent another extratubular stem cell niche. The fundamental unanswered questions in this field include whether renal stem cells exist in the adult, and if they do where are they located (interstitium, tubule, cortex, medulla) and what markers can be relied upon for the isolation and purification of these putative renal stem cells. In this review we focus on our current understanding of the potential role of renal and extrarenal stem cells in repair of the adult kidney and highlight some of the controversies in this field.
肾脏在损伤后具有显著的再生能力。干细胞是否是替代受损和即将死亡的肾小管上皮的上皮祖细胞来源，目前是一个深入研究的领域。我们实验室和其他机构的研究支持了一种模型，即损伤后许多存活的肾上皮细胞去分化并呈现间充质特征。这些细胞增殖以恢复裸露基底膜的完整性，随后再分化为功能性上皮。另一种可能性是，少数存活的肾小管内细胞具有干细胞特性，并在邻近细胞受损后选择性增殖。有一些证据支持这一假说，但尚未得到严格评估。第三个假说是，肾外细胞有助于受损上皮的修复。有人提出骨髓来源的干细胞参与这一过程，但我们和其他人的研究表明，绝大多数肾小管细胞来源于肾内。最近的证据表明，间质细胞可能代表另一个肾外干细胞龛。该领域尚未解决的基本问题包括成体中是否存在肾干细胞，如果存在，它们位于何处（间质、肾小管、皮质、髓质），以及可以依靠哪些标志物来分离和纯化这些假定的肾干细胞。在这篇综述中，我们重点阐述了目前对肾内和肾外干细胞在成体肾脏修复中潜在作用的理解，并突出了该领域的一些争议。
