Bone marrow-derived CXCR4-overexpressing MSCs display increased homing to intestine and ameliorate colitis-associated tumorigenesis in mice

Zheng, Xiaobin; He, Xiaowen; Zhang, Longjuan; Qin, Huabo; Lin, Xutao; Liu, Xuanhui; Zhou, Chang; Liu, Huashan; Hu, Tuo; Cheng, Haichun; He, Xiaosheng; Wu, Xianrui; Chen, Yufeng; Ke, Jia; Wu, Xiaojian; Lan, Ping

doi:10.1093/gastro/goy017

Cited by 56 publications

(44 citation statements)

References 69 publications

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“…Likewise, in chronic kidney disease, there is low level homing and poor survival of transplanted marrow‐derived MSCs 126 . In mice, marrow‐derived CXCR4‐overexpressing MSCs homed to the intestine and improved colitis in inflammatory bowel disease states 127 . Some of this differential ability to home is target tissue‐dependent, but intrinsic MSC alterations can also explain this varied capacity.…”

Section: Msc Homingmentioning

confidence: 99%

Stem cell homing: From physiology to therapeutics

2020

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Stem cell homing is a multistep endogenous physiologic process that is also used by exogenously administered hematopoietic stem and progenitor cells (HSPCs). This multistep process involves cell migration and is essential for hematopoietic stem cell transplantation. The process can be manipulated to enhance ultimate engraftment potential, and understanding stem cell homing is also important to the understanding of stem cell mobilization. Homing is also of potential importance in the recruitment of marrow mesenchymal stem and stromal cells (MSCs) to sites of injury and regeneration. This process is less understood but assumes importance when these cells are used for repair purposes. In this review, the process of HSPC and MSC homing is examined, as are methods to enhance this process.

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Section: Msc Homingmentioning

confidence: 99%

Stem cell homing: From physiology to therapeutics

2020

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“…Later, using the same murine model of colitis, it was demonstrated that AMD3100 also enhanced epithelial barrier integrity (245). A recent report has suggested a role of CXCR4 in mesenchymal stem cells (MSCs) homing to the inflamed intestinal tissues (246). MSCs play an important role in tissue repair and regeneration but also have immunoregulatory properties that might contribute to reduce inflammation (247).…”

Section: Cxcl12/cxcr4/ackr3 In Autoimmune Diseasesmentioning

confidence: 99%

The Role of the CXCL12/CXCR4/ACKR3 Axis in Autoimmune Diseases

et al. 2019

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Chemokine receptors are members of the G protein-coupled receptor superfamily. These receptors are intimately involved in cell movement, and thus play a critical role in several physiological and pathological situations that require the precise regulation of cell positioning. CXCR4 is one of the most studied chemokine receptors and is involved in many functions beyond leukocyte recruitment. During embryogenesis, it plays essential roles in vascular development, hematopoiesis, cardiogenesis, and nervous system organization. It has been also implicated in tumor progression and autoimmune diseases and, together with CD4, is one of the co-receptors used by the HIV-1 virus to infect immune cells. In contrast to other chemokine receptors that are characterized by ligand promiscuity, CXCR4 has a unique ligand—stromal cell-derived factor-1 (SDF1, CXCL12). However, this ligand also binds ACKR3, an atypical chemokine receptor that modulates CXCR4 functions and is overexpressed in multiple cancer types. The CXCL12/CXCR4/ACKR3 axis constitutes a potential therapeutic target for a wide variety of inflammatory diseases, not only by interfering with cell migration but also by modulating immune responses. Thus far, only one antagonist directed against the ligand-binding site of CXCR4, AMD3100, has demonstrated clinical relevance. Here, we review the role of this ligand and its receptors in different autoimmune diseases.

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“…Analogously, Liu et al 61 enforced surface expression of CXCR4 by lentiviral gene transfer in BM-MSCs to protect against experimental colitis via promoting the homing of BM-MSCs to inflamed colon where these cells could reduce inflammatory responses and suppress signal transducer and activator of transcription 3 (STAT3) phosphorylation. In addition, Zheng et al 62 also found that azoxymethane (AOM) and DSS-induced colitis-associated tumorigenesis were significantly attenuated when CXCR4-upregulated BM-MSCs were administrated. Interestingly, Nan et al 63 used the same method to enhance the expression of CXCR4 and IL-35 in BM-MSCs simultaneously.…”

Section: Improves the Efficacy Of Mscsmentioning

confidence: 99%

Potential methods for improving the efficacy of mesenchymal stem cells in the treatment of inflammatory bowel diseases

et al. 2020

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Inflammatory bowel diseases (IBD) are a group of chronic recurrent gastrointestinal inflammatory diseases, including ulcerative colitis (UC), Crohn's disease (CD) and IBD unclassified. The pathogenesis may be related to the mucosal immune dysfunction in genetically susceptible hosts affected by environmental factors. Current therapeutic agents mainly include aminosalicylates, corticosteroids, immunosuppressive drugs and novel biological agents. The purpose of treatment is to suppress inflammation and prevent irreversible structural damage. However, long‐term application of these drugs may lead to multiple adverse effects and is not always effective. Mesenchymal stem cells (MSCs) are multipotent progenitors with low immunogenicity, which can be obtained and expanded easily. They play an important role in regulating immune responses and repairing damaged tissues in vivo. Therefore, MSCs are considered to be a promising option for the treatment of IBD. Nonetheless, there are many factors that can reduce the efficacy of MSCs, such as gradual deterioration of functional stem cells with age, low recruitment and persistence in vivo and different routes of administration. In recent years, researchers have been able to improve the efficacy of MSCs by pretreatment, genetic modification or co‐application with other substances, as well as using different tissue‐derived cells, administration methods or doses. This article reviews these methods to provide references for more effective application of MSCs in the treatment of IBD in the future.

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Bone marrow-derived CXCR4-overexpressing MSCs display increased homing to intestine and ameliorate colitis-associated tumorigenesis in mice

Cited by 56 publications

References 69 publications

Stem cell homing: From physiology to therapeutics

Stem cell homing: From physiology to therapeutics

The Role of the CXCL12/CXCR4/ACKR3 Axis in Autoimmune Diseases

Potential methods for improving the efficacy of mesenchymal stem cells in the treatment of inflammatory bowel diseases

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