Mayo Clinic, Division of Nephrology and Hypertension, Rochester, MN 55905, USA.
Department of Medicine University of Missouri, Kansas, MO 64108, USA.
Cells. 2021 Mar 31;10(4):765. doi: 10.3390/cells10040765.
Ischemic nephropathy reflects progressive loss of kidney function due to large vessel atherosclerotic occlusive disease. Recent studies indicate that this process is characterized by microvascular rarefaction, increased tissue hypoxia and activation of inflammatory processes of tissue injury. This review summarizes the rationale and application of functional MR imaging to evaluate tissue oxygenation in human subjects that defines the limits of renal adaptation to reduction in blood flow, development of increasingly severe tissue hypoxia and recruitment of inflammatory injury pathways in ischemic nephropathy. Human mesenchymal stromal/stem cells (MSC) are capable of modifying angiogenic pathways and immune responses, but the potency of these effects vary between individuals and various clinical characteristics including age and chronic kidney disease and levels of hypoxia. We summarize recently completed first-in-human studies applying intrarenal infusion of autologous adipose-derived MSC in human subjects with ischemic nephropathy that demonstrate a rise in blood flow and reduction in tissue hypoxia consistent with partial repair of microvascular injury, even without restoring main renal arterial blood flow. Inflammatory biomarkers in the renal vein of post-stenotic kidneys fell after MSC infusion. These changes were associated with modest but significant dose-related increments in kidney function. These data provide support a role for autologous MSC in repair of microvascular injury associated with tissue hypoxia.
缺血性肾病反映了由于大血管动脉粥样硬化闭塞性疾病导致的肾功能进行性丧失。最近的研究表明，这个过程的特征是微血管稀疏、组织缺氧增加和组织损伤的炎症过程激活。这篇综述总结了功能磁共振成像在评估人类组织氧合方面的原理和应用，该方法定义了肾脏对血流减少的适应极限、组织缺氧程度的逐渐加重以及缺血性肾病中炎症损伤途径的招募。人骨髓间充质基质/干细胞（MSC）能够调节血管生成途径和免疫反应，但这些作用的效力在个体之间以及各种临床特征（包括年龄、慢性肾脏病和缺氧水平）之间存在差异。我们总结了最近完成的首例人体研究，这些研究将自体脂肪来源的 MSC 肾内输注应用于缺血性肾病患者，结果显示血流增加，组织缺氧减少，与微血管损伤的部分修复一致，即使没有恢复主要肾动脉血流也是如此。MSC 输注后狭窄后肾静脉中的炎症生物标志物下降。这些变化与肾功能的适度但显著的剂量相关增加相关。这些数据支持自体 MSC 在修复与组织缺氧相关的微血管损伤中的作用。
