Dataset Information

Bone marrow-derived cells can acquire renal stem cells properties and ameliorate ischemia-reperfusion induced acute renal injury.

ABSTRACT:

Background

Bone marrow (BM) stem cells have been reported to contribute to tissue repair after kidney injury model. However, there is no direct evidence so far that BM cells can trans-differentiate into renal stem cells.

Methods

To investigate whether BM stem cells contribute to repopulate the renal stem cell pool, we transplanted BM cells from transgenic mice, expressing enhanced green fluorescent protein (EGFP) into wild-type irradiated recipients. Following hematological reconstitution and ischemia-reperfusion (I/R), Sca-1 and c-Kit positive renal stem cells in kidney were evaluated by immunostaining and flow cytometry analysis. Moreover, granulocyte colony stimulating factor (G-CSF) was administrated to further explore if G-CSF can mobilize BM cells and enhance trans-differentiation efficiency of BM cells into renal stem cells.

Results

BM-derived cells can contribute to the Sca-1(+) or c-Kit(+) renal progenitor cells population, although most renal stem cells came from indigenous cells. Furthermore, G-CSF administration nearly doubled the frequency of Sca-1+ BM-derived renal stem cells and increased capillary density of I/R injured kidneys.

Conclusions

These findings indicate that BM derived stem cells can give rise to cells that share properties of renal resident stem cell. Moreover, G-CSF mobilization can enhance this effect.

SUBMITTER: Jia X

PROVIDER: S-EPMC3505151 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Publications

Bone marrow-derived cells can acquire renal stem cells properties and ameliorate ischemia-reperfusion induced acute renal injury.

Jia Xiaohua X Xie Xiaoqiang X Feng Guowei G Lű He H Zhao Qinjun Q Che Yongzhe Y Zheng Yizhou Y Han Zhongchao Z Xu Yong Y Li Zongjin Z Kong Deling D

BMC nephrology 20120910

<h4>Background</h4>Bone marrow (BM) stem cells have been reported to contribute to tissue repair after kidney injury model. However, there is no direct evidence so far that BM cells can trans-differentiate into renal stem cells.<h4>Methods</h4>To investigate whether BM stem cells contribute to repopulate the renal stem cell pool, we transplanted BM cells from transgenic mice, expressing enhanced green fluorescent protein (EGFP) into wild-type irradiated recipients. Following hematological recons ...[more]

PMID: 22963129

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Project description:BackgroundAcute kidney injury (AKI) is an emerging global healthcare issue without effective therapy yet. Autophagy recycles damaged organelles and helps maintain tissue homeostasis in acute renal ischemia-reperfusion (I/R) injury. Hypoxic mesenchymal stem cells (HMSCs) represent an innovative cell-based therapy in AKI. Moreover, the conditioned medium of HMSCs (HMSC-CM) rich in beneficial trophic factors may serve as a cell-free alternative therapy. Nonetheless, whether HMSCs or HMSC-CM mitigate renal I/R injury via modulating tubular autophagy remains unclear.MethodsRenal I/R injury was induced by clamping of the left renal artery with right nephrectomy in male Sprague-Dawley rats. The rats were injected with either PBS, HMSCs, or HMSC-CM immediately after the surgery and sacrificed 48 h later. Renal tubular NRK-52E cells subjected to hypoxia-reoxygenation (H/R) injury were co-cultured with HMSCs or treated with HMSC-CM to assess the regulatory effects of HSMCs on tubular autophagy and apoptosis. The association of tubular autophagy gene expression and renal recovery was also investigated in patients with ischemic AKI.ResultHMSCs had a superior anti-oxidative effect in I/R-injured rat kidneys as compared to normoxia-cultured mesenchymal stem cells. HMSCs further attenuated renal macrophage infiltration and inflammation, reduced tubular apoptosis, enhanced tubular proliferation, and improved kidney function decline in rats with renal I/R injury. Moreover, HMSCs suppressed superoxide formation, reduced DNA damage and lipid peroxidation, and increased anti-oxidants expression in renal tubular epithelial cells during I/R injury. Co-culture of HMSCs with H/R-injured NRK-52E cells also lessened tubular cell death. Mechanistically, HMSCs downregulated the expression of pro-inflammatory interleukin-1β, proapoptotic Bax, and caspase 3. Notably, HMSCs also upregulated the expression of autophagy-related LC3B, Atg5 and Beclin 1 in renal tubular cells both in vivo and in vitro. Addition of 3-methyladenine suppressed the activity of autophagy and abrogated the renoprotective effects of HMSCs. The renoprotective effect of tubular autophagy was further validated in patients with ischemic AKI. AKI patients with higher renal LC3B expression were associated with better renal recovery.ConclusionThe present study describes that the enhancing effect of MSCs, and especially of HMCSs, on tissue autophagy can be applied to suppress renal tubular apoptosis and attenuate renal impairment during renal I/R injury in the rat. Our findings provide further mechanistic support to HMSCs therapy and its investigation in clinical trials of ischemic AKI.

Project description:BackgroundHypoxia preconditioning has been proven to be an effective method to enhance the therapeutic action of mesenchymal stem cells (MSCs). However, the beneficial effects of hypoxic MSCs in ischemia/reperfusion (I/R) lung injury have yet to be investigated. In this study, we hypothesized that the administration of hypoxic MSCs would have a positive therapeutic impact on I/R lung injury at molecular, cellular, and functional levels.MethodsI/R lung injury was induced in isolated and perfused rat lungs. Hypoxic MSCs were administered in perfusate at a low (2.5×105 cells) and high (1×106 cells) dose. Rats ventilated with a low tidal volume of 6 ml/kg served as controls. Hemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined.ResultsI/R induced permeability pulmonary edema with capillary leakage and increased levels of reactive oxygen species (ROS), pro-inflammatory cytokines, adhesion molecules, cytosolic cytochrome C, and activated MAPK, NF-κB, and apoptotic pathways. The administration of a low dose of hypoxic MSCs effectively attenuated I/R pathologic lung injury score by inhibiting inflammatory responses associated with the generation of ROS and anti-apoptosis effect, however this effect was not observed with a high dose of hypoxic MSCs. Mechanistically, a low dose of hypoxic MSCs down-regulated P38 MAPK and NF-κB signaling but upregulated glutathione, prostaglandin E2, IL-10, mitochondrial cytochrome C and Bcl-2. MSCs infused at a low dose migrated into interstitial and alveolar spaces and bronchial trees, while MSCs infused at a high dose aggregated in the microcirculation and induced pulmonary embolism.ConclusionsHypoxic MSCs can quickly migrate into extravascular lung tissue and adhere to other inflammatory or structure cells and attenuate I/R lung injury through anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms. However, the dose of MSCs needs to be optimized to prevent pulmonary embolism and thrombosis.

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Dataset Information

Bone marrow-derived cells can acquire renal stem cells properties and ameliorate ischemia-reperfusion induced acute renal injury.

Background

Methods

Results

Conclusions

Publications

Bone marrow-derived cells can acquire renal stem cells properties and ameliorate ischemia-reperfusion induced acute renal injury.

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