Hypoxia Preconditioning Promotes the Proliferation and Migration of Human Urine-Derived Stem Cells in Chronically Injured Liver of Mice by Upregulating <i>CXCR4</i>

Hu, Chaoqun; Liu, Daijiang; Zhao, Li; Fang, Shuyu; Tan, Bin; Dong, Shi-Fang; Wang, Yi; He, Tong‐Chuan; Bi, Yang

doi:10.1089/scd.2021.0008

Cited by 14 publications

(8 citation statements)

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“…Although naïve MSCs are still the most common approach used to treat ICH, researches are being conducted to discover several methods to culture more functional MSCs, including pharmacologic pre-conditioning [ 54 ], alternative cell delivery approaches [ 55 – 57 ], genetic modification [ 58 , 59 ], physical methods [ 60 ], and modification of culture conditions [ 14 , 17 ]. Hypoxic preconditioning is a modification of culture conditions that have been shown to improve the therapeutic efficacy of stem cells in a model of atherosclerotic renal artery stenosis [ 61 ], spinal cord injury [ 62 ], ischemic stroke [ 18 , 63 , 64 ], acute lung injury [ 65 ], myocardial infarction [ 15 ], chronic liver injury [ 66 ], urethral injury [ 67 ], and ICH [ 14 , 17 ]. The oxygen concentrations evaluated in most of these studies include 0.1–0.3% O 2 , 1% O 2 , 3% O 2 , and 5% O 2 , and the treatment durations range from 24 to 48 h. In a general setting, MSCs are cultured under normoxia niche (~21%) [ 68 ].…”

Section: Resultsmentioning

confidence: 99%

Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy

Liu

et al. 2021

Stem Cell Res Ther

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Background Intracerebral hemorrhage (ICH) is a major public health concern, and mesenchymal stem cells (MSCs) hold great potential for treating ICH. However, the quantity and quality of MSCs decline in the cerebral niche, limiting the potential efficacy of MSCs. Hypoxic preconditioning is suggested to enhance the survival of MSCs and augment the therapeutic efficacy of MSCs in ICH. MicroRNAs (miRNAs) are known to mediate cellular senescence. However, the precise mechanism by which miRNAs regulate the senescence of hypoxic MSCs remains to be further studied. In the present study, we evaluated whether hypoxic preconditioning enhances the survival and therapeutic effects of olfactory mucosa MSC (OM-MSC) survival and therapeutic effects in ICH and investigated the mechanisms by which miRNA ameliorates hypoxic OM-MSC senescence. Methods In the in vivo model, ICH was induced in mice by administration of collagenase IV. At 24 h post-ICH, 5 × 105 normoxia or hypoxia OM-MSCs or saline was administered intracerebrally. The behavioral outcome, neuronal apoptosis, and OM-MSC survival were evaluated. In the in vitro model, OM-MSCs were exposed to hemin. Cellular senescence was examined by evaluating the expressions of P16INK4A, P21, P53, and by β-galactosidase staining. Microarray and bioinformatic analyses were performed to investigate the differences in the miRNA expression profiles between the normoxia and hypoxia OM-MSCs. Autophagy was confirmed using the protein expression levels of LC3, P62, and Beclin-1. Results In the in vivo model, transplanted OM-MSCs with hypoxic preconditioning exhibited increased survival and tissue-protective capability. In the in vitro model, hypoxia preconditioning decreased the senescence of OM-MSCs exposed to hemin. Bioinformatic analysis identified that microRNA-326 (miR-326) expression was significantly increased in the hypoxia OM-MSCs compared with that of normoxia OM-MSCs. Upregulation of miR-326 alleviated normoxia OM-MSC senescence, whereas miR-326 downregulation increased hypoxia OM-MSC senescence. Furthermore, we showed that miR-326 alleviated cellular senescence by upregulating autophagy. Mechanistically, miR-326 promoted the autophagy of OM-MSCs via the PI3K signaling pathway by targeting polypyrimidine tract-binding protein 1 (PTBP1). Conclusions Our study shows that hypoxic preconditioning delays OM-MSC senescence and augments the therapeutic efficacy of OM-MSCs in ICH by upregulating the miR-326/PTBP1/PI3K-mediated autophagy.

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Section: Resultsmentioning

confidence: 99%

Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy

Liu

et al. 2021

Stem Cell Res Ther

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“…It has been reported that after hypoxic pretreatment, the liver recovery efficiency of USCs is slightly enhanced by the induction of autophagy in a chronic liver fibrosis mouse model ( Hu et al, 2020 ). In addition, C-X-C motif chemokine (CXC) receptor 4 (CXCR4) was significantly upregulated in USCs after hypoxic preconditioning and then interacted with the (CXC) ligand 12 (CXCL12) (an important chemokine for cell transport and homing) expressed at high levels in damaged liver tissues, thus promoting the proliferation, colony formation and migration of USCs ( Hu et al, 2021 ). Moreover, the cell fusion rate between USCs and hepatocytes was increased after hypoxic preconditioning, and these polyploid stem cells may be involved in liver regeneration ( Hu et al, 2021 ).…”

Section: Applications Of Uscsmentioning

confidence: 99%

“…In addition, C-X-C motif chemokine (CXC) receptor 4 (CXCR4) was significantly upregulated in USCs after hypoxic preconditioning and then interacted with the (CXC) ligand 12 (CXCL12) (an important chemokine for cell transport and homing) expressed at high levels in damaged liver tissues, thus promoting the proliferation, colony formation and migration of USCs ( Hu et al, 2021 ). Moreover, the cell fusion rate between USCs and hepatocytes was increased after hypoxic preconditioning, and these polyploid stem cells may be involved in liver regeneration ( Hu et al, 2021 ). All of these findings confirm the value of hypoxic preconditioning in improving the therapeutic efficacy of USCs in patients with end-stage liver disease.…”

Section: Applications Of Uscsmentioning

confidence: 99%

A Comprehensive Review of the Therapeutic Value of Urine-Derived Stem Cells

et al. 2022

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Stem cells possess regenerative powers and multidirectional differentiation potential and play an important role in disease treatment and basic medical research. Urine-derived stem cells (USCs) represent a newly discovered type of stem cell with biological characteristics similar to those of mesenchymal stromal cells (MSCs), including their doubling time and immunophenotype. USCs are noninvasive and can be readily obtained from voided urine and steadily cultured. Based on advances in this field, USCs and their secretions have increasingly emerged as ideal sources. USCs may play regulatory roles in the cellular immune system, oxidative stress, revascularization, apoptosis and autophagy. This review summarizes the applications of USCs in tissue regeneration and various disease treatments. Furthermore, by analysing their limitations, we anticipate the development of more feasible therapeutic strategies to promote USC-based individualized treatment.

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“…Urine-derived stem cells (USCs) have strong self-renewal capacity and multi-directional differentiation potential. Hypoxia preconditioning promotes the proliferation, migration and cell fusion of USCs by inducing CXCR4 signaling, leading to liver tissue recovery following injury ( Hu et al, 2021 ). Based on the mechanism of the CXCL12/CXCR4 axis, the systemically transplanted adipose-derived stem cells (ADSCs) home to the injured liver after transplantation can stimulate liver regeneration in hepatectomy and I/R injured model mice ( Saito et al, 2014 ).…”

Section: The Protective Effect Of Cxcr4 Signaling Pathway In Acute Liver Injury and Regenerationmentioning

confidence: 99%

Emerging Importance of Chemokine Receptor CXCR4 and Its Ligand in Liver Disease

Wang

Gao

et al. 2021

Front. Cell Dev. Biol.

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Chemokine receptors are members of the G protein-coupled receptor superfamily, which together with chemokine ligands form chemokine networks to regulate various cellular functions, immune and physiological processes. These receptors are closely related to cell movement and thus play a vital role in several physiological and pathological processes that require regulation of cell migration. CXCR4, one of the most intensively studied chemokine receptors, is involved in many functions in addition to immune cells recruitment and plays a pivotal role in the pathogenesis of liver disease. Aberrant CXCR4 expression pattern is related to the migration and movement of liver specific cells in liver disease through its cross-talk with a variety of significant cell signaling pathways. An in-depth understanding of CXCR4-mediated signaling pathway and its role in liver disease is critical to identifying potential therapeutic strategies. Current therapeutic strategies for liver disease mainly focus on regulating the key functions of specific cells in the liver, in which the CXCR4 pathway plays a crucial role. Multiple challenges remain to be overcome in order to more effectively target CXCR4 pathway and identify novel combination therapies with existing strategies. This review emphasizes the role of CXCR4 and its important cell signaling pathways in the pathogenesis of liver disease and summarizes the targeted therapeutic studies conducted to date.

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Hypoxia Preconditioning Promotes the Proliferation and Migration of Human Urine-Derived Stem Cells in Chronically Injured Liver of Mice by Upregulating CXCR4

Cited by 14 publications

References 38 publications

Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy

Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy

A Comprehensive Review of the Therapeutic Value of Urine-Derived Stem Cells

Emerging Importance of Chemokine Receptor CXCR4 and Its Ligand in Liver Disease

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