未成熟牙髓干细胞在大鼠急性肾衰竭中表现出嗜肾性和周细胞样特性。

M. A. Barros, J. P. F. Martins, D. Maria, Crisitiane Valverde Wenceslau, Dener Madeiro de Souza, A. Kerkis, N. Câmara, J. Balieiro, I. Kerkis
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引用次数: 19

摘要

急性肾功能衰竭(ARF)是一种常见的肾脏疾病,可导致高死亡率。ARF的恢复伴随着坏死小管细胞被功能性小管上皮细胞所取代,以及小管周围毛细血管微血管内皮细胞功能的正常化。传统的治疗技术往往对ARF无效。因此,通过多种营养和再生机制发挥作用的干细胞疗法是令人鼓舞的。我们研究了肌内注射甘油诱导ARF的免疫活性Wistar大鼠,在不使用免疫抑制的情况下,静脉(EV)或腹腔(IP)注射人未成熟牙髓干细胞(IDPSCs)的归巢情况。冷冻保存6年的细胞为CD105(+)、CD73(+)、CD44(+),部分为STRO-1(+)和CD146(+),具有不变的中胚层分化潜能。这些细胞存在于肾小管区和小管周围毛细血管中。这些细胞通过显著增加ki -67免疫反应细胞促进肾小管上皮细胞再生。流式细胞术分析证实IDPSCs归巢于肾脏(EV为34.10%,IP为33.25%);肝脏(19.05%,IP 9.10%)、肌肉(6.30%,IP 1.35%)和肺部(2.0%,IP 1.85%)的细胞比例较低。注入大鼠后,这些细胞表达周细胞标记物,如CD146(+)、STRO-1(+)和血管内皮生长因子(VEGF(+))。在实验大鼠ARF模型中,我们发现IDPSCs具有嗜肾性和周细胞样特性,并有助于恢复肾小管结构。
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Immature Dental Pulp Stem Cells Showed Renotropic and Pericyte-Like Properties in Acute Renal Failure in Rats.
Acute renal failure (ARF) is a common renal disease that can lead to high mortality. Recovery from ARF occurs with the replacement of necrotic tubular cells by functional tubular epithelial cells and the normalization of microvascular endothelial cell function in the peritubular capillaries. Conventional therapeutic techniques are often ineffective against ARF. Hence, stem cell therapies, which act through multiple trophic and regenerative mechanisms, are encouraging. We investigated the homing of human immature dental pulp stem cells (IDPSCs) after endovenous (EV) or intraperitoneal (IP) injection, in immunocompetent Wistar rats with ARF induced by intramuscular injection of glycerol, without the use of immunosuppression. The cells, which had been cryopreserved for 6 years, were CD105(+), CD73(+), CD44(+), and partly, STRO-1(+) and CD146(+), and presented unaltered mesoderm differentiation potential. The presence of these cells in the tubular region of the kidney and in the peritubular capillaries was demonstrated. These cells accelerate tubular epithelial cell regeneration through significant increase of Ki-67-immunoreactive cells in damaged kidney. Flow cytometry analysis confirmed that IDPSCs home to the kidneys (EV 34.10% and IP 33.25%); a lower percentage of cells was found in the liver (EV 19.05% and IP 9.10%), in the muscles (EV 6.30% and IP 1.35%), and in the lungs (EV 2.0% and IP 1.85%). After infusion into rat, these cells express pericyte markers, such as CD146(+), STRO-1(+), and vascular endothelial growth factor (VEGF(+)). We found that IDPSCs demonstrate renotropic and pericyte-like properties and contributed to restore renal tubule structure in an experimental rat ARF model.
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Cell medicine
Cell medicine MEDICINE, RESEARCH & EXPERIMENTAL-
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