CXCL12/CXCR4 axis promotes mesenchymal stem cell mobilization to burn wounds and contributes to wound repair

Hu, C.; Xin, Yong; Li, Changzhu; Lü, Muhan; Liu, Dengqun; Chen, Lin; Hu, Jiongyu; Teng, Miao; Zhang, Dongxia; Fan, Yuxia; Liang, Guangping

doi:10.1016/j.jss.2013.01.019

Cited by 130 publications

(108 citation statements)

References 27 publications

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“…Migration of implanted MSCs to the injury site is mediated by matrix metalloproteinases [26]. Retained MSCs play a role in damage repair by differentiating into different types of connective tissue [27], promoting angiogenesis [28] and exerting anti-inflammatory effect [29, 30].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability

Zhu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Radiation therapy is an important treatment for thoracic cancer; however, side effects accompanied with radiotherapy lead to limited tumor control and a decline in patient quality of life. Among these side effects, radiation-induced lung injury (RILI) is the most serious and common. Hence, an effective remedy for RILI is needed. Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that have been demonstrated to be an effective treatment in some disease caused by tissue damage. However, unlike other injuries, RILI received limited therapeutic effects from implanted MSCs due to local hypoxia and extensive reactive oxygen species (ROS) in irradiated lungs. Since the poor survival of MSCs is primarily due to hypoxia and ROS generation, we hypothesize that persistent and adaptive hypoxia treatment induces enhanced resistance to hypoxic stress in implanted MSC. The aim of this study is to investigate whether persistent and adaptive hypoxia treatment of bmMSCs prior to their transplantation in injured mice enhanced survival and improved curative effects in RILI. Methods: Primary bmMSCs were obtained from the marrow of six-week-old male C57BL6/J mice and were cultured either under normoxic conditions (21% O₂) or hypoxic conditions (2.5% O₂). Mice were injected with normoxia/hypoxia MSCs after thoracic irradiation (20 Gy). The therapeutic effects of MSCs on RILI were assessed by pathological examinations that included H&E staining, Masson staining and α-SMA staining; meanwhile, inflammatory factors were measured using an ELISA. The morphology of MSCs in vitro was recorded using a microscope and identified by flow cytometry, cell viability was measured using the CCK-8 assay, the potential for proliferation was detected by the EdU assay, and ROS levels were measured using a ROS fluorogenic probe. In addition, HIF-1α and several survival pathway proteins (Akt, p-Akt, Caspase-3) were also detected by western blotting. Results: Implanted MSCs alleviated both early radiation-induced pneumonia and late pulmonary fibrosis. However, hypoxia MSCs displayed a more pronounced therapeutic effect compared to normoxia MSCs. Compared to normoxia MSCs, the hypoxia MSCs demonstrated greater cell viability, an enhanced proliferation potential, decreased ROS levels and increased resistance to hypoxia and ROS stress. In addition, hypoxia MSCs achieved higher activation levels of HIF-1α and Akt, and HIF-1α played a critical role in the development of resistance. Conclusion: Hypoxia enhances the therapeutic effect of mesenchymal stromal cells on radiation-induced lung injury by promoting MSC proliferation and improving their antioxidant ability, mediated by HIF-1α.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability

Zhu

et al. 2017

Cell Physiol Biochem

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“…40 The knockdown result has been recently confirmed in a study that preincubated MSCs with a CXCR4 antagonist prior to intravenous injection. 41 This resulted in diminished numbers of MSCs in a burn wound. Collectively, these studies demonstrate that the CXCL12-CXCR4 axis regulates stem cell homing to wounds.…”

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confidence: 99%

The Role of Chemokines in Mesenchymal Stem Cell Homing to Wounds

Hocking

2015

Advances in Wound Care

138

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Significance: Mesenchymal stem cells (MSCs) are being administered to cutaneous wounds with the goal of accelerating wound closure and promoting regeneration instead of scar formation. An ongoing challenge for cell-based therapies is achieving effective and optimal targeted delivery and engraftment at the site of injury. Contributing to this challenge is our incomplete understanding of endogenous MSC homing to sites of injury. Recent Advances: Chemokines and their receptors are now recognized as important mediators of stem cell homing. To date, the most studied chemokinechemokine receptor axis in MSC homing to wounds is CXCL12-CXCR4 but recent work suggests that CCL27-CCR10 and CCL21-CCR7 may also be involved. Critical Issues: Strategies to enhance chemokine-mediated MSC homing to wounds are using a variety of approaches to amplify the chemokine signal at the wound site and/or overexpress specific chemokine receptors on the surface of the MSC. Future Directions: Harnessing chemokine signaling may enhance the therapeutic effects of stem cell therapy by increasing the number of both exogenous and endogenous stem cells recruited to the site of injury. Alternatively, chemokine-based therapies directly targeting endogenous stem cells may circumvent the need for the time-consuming and costly isolation and expansion of autologous stem cells prior to therapeutic administration. SCOPE AND SIGNIFICANCEMesenchymal stem cells (MSCs) are being administered to cutaneous wounds with the goal of accelerating wound closure and promoting regeneration instead of scar formation.1 An ongoing challenge for cell-based therapies is achieving effective and optimal targeted delivery and engraftment at the site of injury. Contributing to this challenge is our incomplete understanding of endogenous MSC homing to sites of injury.2 This review will summarize our current knowledge about the role of chemokines in MSC recruitment to wounds. TRANSLATIONAL RELEVANCEThe translational relevance for research defining the chemokines responsible for stem cell homing is significant with a direct impact on stem cell therapy. Harnessing chemokine signaling may enhance the therapeutic effects of stem cell therapy by increasing the number of both exogenous and endogenous stem cells recruited to the site of injury. Alternatively, chemokine-based therapies directly targeting endogenous stem cells may circumvent the need for the time-consuming and costly isolation and expansion of autologous stem cells prior to therapeutic administration. CLINICAL RELEVANCEOngoing clinical trials are investigating the safety and efficacy of MSC therapy for the treatment of

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“…Human-beings try to find effective measures to realize regeneration of the damaged tissues from non-surgical mechanical debridement to periodontal surgery and pharmaceutical therapy [5].Regenerative stem cell therapy has created a lot of hope among scientists and physicians for finding more effective treatment strategies to reconstruct damaged periodontium [6]. Recent studies have reported that the chemokine SDF-1 and its receptor CXCR4 play an important role in stem cell migration, chemotaxis,homing and differentiation [7]. SDF-1 also significantly increased the chemotaxis of mesenchymal stem cells with increasing of the expression of CXCR4 in the mesenchymal stem cells transfected with CXCR4 gene [8], whereas inhibited mesenchymal stem cell pairs by blocking the expression of CXCR4 [9].Therefore, apply SDF-1 to teeth tissue engineering to induce stem / progenitor cells to damaged periodontal groups weaving repair will be a promising development direction [10].…”

Section: Discussionmentioning

confidence: 99%

The effect of osteogenic differentiation of Periodontal Ligament Stem Cells isolated from the periodontium of healthy teeth and periodontitis-affected teeth induced by SDF-1

Wang¹,

He²

2017

Proceedings of the 2017 2nd International Conference on Materials Science, Machinery and Energy Engineering (MSMEE 2017)

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CXCL12/CXCR4 axis promotes mesenchymal stem cell mobilization to burn wounds and contributes to wound repair

Cited by 130 publications

References 27 publications

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability

The Role of Chemokines in Mesenchymal Stem Cell Homing to Wounds

The effect of osteogenic differentiation of Periodontal Ligament Stem Cells isolated from the periodontium of healthy teeth and periodontitis-affected teeth induced by SDF-1

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