Lindoso Rafael S, Araujo Dayana S, Adão-Novaes Juliana, Mariante Rafael M, Verdoorn Karine S, Fragel-Madeira Lucianne, Caruso-Neves Celso, Linden Rafael, Vieyra Adalberto, Einicker-Lamas Marcelo
Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Cell Physiol Biochem. 2011;28(2):267-78. doi: 10.1159/000331739. Epub 2011 Aug 16.
BACKGROUND/AIMS: Renal tubular cells are the main target of ischemic insult associated with acute renal injury. Low oxygen and nutrient supplies result in ATP depletion, leading to cell death and loss of renal function. A possible mechanism by which bone marrow-derived cells support renal tissue regeneration relies on the capacity of mononuclear cells (BMMC), particularly mesenchymal stem cells (MSC), to secrete paracrine factors that mediate support for kidney regeneration.
BMMC/MSC and renal cells (LLC-PK(1) from pig and IRPTC from rat) were co-cultured under stressful conditions (ATP depletion and/or serum free starvation), physically separated by a microporous membrane (0.4 μm), was used to determine whether bone marrow-derived cells can interact with renal cells in a paracrine manner.
This interaction resulted in stimulation of renal cell proliferation and the arrest of cell death. MSC elicit effective responses in renal cells in terms of stimulating proliferation and protection. Such effects are observed in renal cells co-cultured with rat BMMC/MSC, an indication that paracrine mechanisms are not entirely species-specific.
The paracrine action of BMMC/MSC was influenced by a renal cell stimulus released during stress, indicating that cross-talk with injured cells is required for renal regeneration supported by bone marrow-derived cells.
背景/目的:肾小管细胞是与急性肾损伤相关的缺血性损伤的主要靶点。低氧和营养供应导致三磷酸腺苷(ATP)耗竭,进而导致细胞死亡和肾功能丧失。骨髓来源的细胞支持肾组织再生的一种可能机制依赖于单核细胞(BMMC),特别是间充质干细胞(MSC)分泌旁分泌因子的能力,这些因子介导对肾脏再生的支持。
将BMMC/MSC与肾细胞(猪的LLC-PK(1)和大鼠的IRPTC)在应激条件下(ATP耗竭和/或无血清饥饿)共培养,通过微孔膜(0.4μm)进行物理分离,以确定骨髓来源的细胞是否能以旁分泌方式与肾细胞相互作用。
这种相互作用导致肾细胞增殖受到刺激,细胞死亡停止。MSC在刺激增殖和保护方面能在肾细胞中引发有效反应。在与大鼠BMMC/MSC共培养的肾细胞中观察到了这种效应,这表明旁分泌机制并非完全具有物种特异性。
BMMC/MSC的旁分泌作用受到应激期间释放的肾细胞刺激的影响,这表明骨髓来源的细胞支持的肾脏再生需要与受损细胞进行相互作用。