Effect of Stem Cell Factor and Granulocyte-Macrophage Colony-Stimulating Factor-Induced Bone Marrow Stem Cell Mobilization on Recovery from Acute Tubular Necrosis in Rats

Abstract

Background: Acute tubular necrosis (ATN) is the most common reason for acute kidney injury (AKI), and there is still an absence of effective therapies. Objective: To assess the value of bone marrow cell mobilization by stem cell factor (SCF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy in rats with gentamicin-induced ATN. Methods: ATN was induced in male Sprague-Dawley (SD) rats with five daily high-dose intraperitoneal injections of gentamicin. Subcutaneous injections of SCF and GM-CSF were administered simultaneously and these cytokines were observed on days 2, 5, 10, 17, 24, and 31. Peripheral blood and renal tissue CD34+ cell count, mortality rate, blood urea nitrogen (BUN), serum creatinine (SCr), creatinine clearance rate (CCr), and histopathologic lesion scores were determined. Twelve hours after bone marrow ablation (BMA) by lethal X-ray radiation, specific pathogen-free (SPF) ATN rats were given five daily injections of SCF and GM-CSF. BUN, SCr, and histopathologic lesion scores were evaluated on days 2, 5, and 10. Results: Peripheral blood CD34+ cell count increased significantly in ATN rats between 2 and 10 days after SCF and GM-CSF injection. Mortality was reduced from 34.7% in the ATN group to 18.6% in the ATN+CSF. In addition, cytokines administration significantly decreased SCr and BUN. Moreover, cytokines rapidly ameliorated tubular injury. There was no significant effect on ATN rats after BMA. Conclusions: This study demonstrated that SCF and GM-CSF effectively mobilized bone marrow cells in ATN rats, and cytokines administration partially prevented gentamicin-induced ATN. These results suggest that bone marrow stem cell (BMSC) mobilization may be an effective therapy for ATN.

Effects of autologous bone marrow-derived stem cell mobilization on acute tubular necrosis and cell apoptosis in rats

“…At least three types of BMSCs are known to exist in the bone marrow: Hematopoietic stem cells, endothelial progenitor cells (EPCs) and mesenchymal stem cells (18). The majority of studies have considered CD34 + cells as BMSCs; therefore, CD34 + cells have been treated as the source cell marker of the biological activities and clinical applications of BMSC mobilization (12,19,20). The differentiation of BMSCs exhibits a certain plasticity (21,22); BMSCs can be horizontally differentiated into other types of tissue cells, including renal tubular epithelial cells.…”

“…Normal rats in the treatment control group were injected with SCF and G-CSF at the same time-points and with the same doses. The SCF and G-SCF doses injected into the rats were based on those described in the literature (12). Since BMSC mobilization causes a peak in the peripheral CD34 + cell population 3-5 days after treatment (13), the fifth day post-intervention day was selected as the starting time-point of detection.…”

Mobilisation of haemopoietic stem cells in teriparatide‐treated patients

“…Furthermore, patients with PHPT show a constant PTH stimulation, which might lead to a more pronounced cytokine response. VEGF, SCF and SDF‐1 are known to stimulate mobilisation of bone marrow‐derived stem cells . Therefore, enhanced endogenous secretion of these factors might represent a mechanism of action of teriparatide induced mobilisation of HSC.…”

“…VEGF, SCF and SDF-1 are known to stimulate mobilisation of bone marrow-derived stem cells. [24][25][26] Therefore, enhanced endogenous secretion of these factors might represent a mechanism of action of teriparatide induced mobilisation of HSC. Nevertheless, VEGF has been shown to correlate with bone marrow density in mini pigs with glucocorticoid-induced osteoporosis.…”

Effect of bone marrow stem cell mobilisation on the expression levels of cellular growth factors in a rat model of acute tubular necrosis

“…The model and treatment groups were established using the unilateral renal ischaemia-reperfusion injury model, based on the method outlined by Supavekin et al (12). After 24 h of modelling, the treatment group was subcutaneously injected once a day with 200 µg/kg SCF (Chengdu Di'ao Jiuhong Pharmaceutical Co., Chengdu, China) and 50 µg/kg G-CSF (North China Pharmaceutical Jintan Biotechnology Co. Ltd, Shijiazhuang, China) for five consecutive days (13). In the treatment control group, the normal rats were injected with SCF and G-CSF at the same time points and with the same doses.…”