CXCR4 Receptor Overexpression in Mesenchymal Stem Cells Facilitates Treatment of Acute Lung Injury in Rats

Yang, Jingxian; Zhang, Nan; Wang, Hanwei; Gao, Peng; Yang, Qing; Wen, Qin

doi:10.1074/jbc.m114.605063

Cited by 130 publications

(106 citation statements)

References 52 publications

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“…The cellular responses are complex, and, in most cases, the pretreatment procedure affects a great number of factors, and not only a single, specific molecule or protein. In contrast, it should be mentioned that another approach to enhance the release of a specific regenerative factor is to overexpress a single factor in MSCs [70,71,72,73,74]. Nevertheless, these genetically engineered MSCs are not reviewed in this article.…”

Section: Concepts Of Msc Preconditioningmentioning

confidence: 99%

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy

Schäfer

Spohn

Baer

2016

Transfus Med Hemother

107

126

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Mesenchymal stem/stromal cells (MSCs) are becoming increasingly important for the development of cell therapeutics in regenerative medicine. Featuring immunomodulatory potential as well as secreting a variety of trophic factors, MSCs showed remarkable therapeutic effects in numerous preclinical disease models. However, sustainable translation of MSC therapies to the clinic is hampered by heterogeneity of MSCs and non-standardized in vitro culture technologies. Moreover, potent MSC therapeutics require MSCs with maximum regenerative capacity. There is growing evidence that in vitro preconditioning strategies of MSCs can optimize their therapeutic potential. In the following we will discuss achievements and challenges of the development of MSC therapies in regenerative medicine highlighting specific in vitro preconditioning strategies prior to cell transplantation to increase their therapeutic efficacy.

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Section: Concepts Of Msc Preconditioningmentioning

confidence: 99%

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy

Schäfer

Spohn

Baer

2016

Transfus Med Hemother

107

126

View full text Add to dashboard Cite

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“…Moreover, one study has demonstrated that facilitating the homing of MSCs to injured lung tissue led to incremental therapeutic benefits. 31 As a response to tissue inflammation, prostaglandin E 2 (PGE 2 ) biosynthesis is upregulated to a large extent. Also, PGE 2 has been shown to promote the migration of MSCs in vitro by stimulation of the EP2 receptor.…”

Section: Mscs-ep2 Treatment For Lung Injurymentioning

confidence: 99%

“…Yang and colleagues demonstrated that the chemokine SDF-1, and the corresponding chemokine receptor 4 (CXCR4), were involved in MSC migration into injured lung tissue and that the overexpressed CXCR4 in MSCs largely improved lung repair in ALI rat models. 41 The increased homing of MSCs to injured lung tissue is the fundamental mechanism of this incremental beneficial effect. However, the precise mechanism is yet an enigma that necessitates further studies.…”

Section: Mscs-ep2 Treatment For Lung Injurymentioning

confidence: 99%

E-Prostanoid 2 Receptor Overexpression Promotes Mesenchymal Stem Cell Attenuated Lung Injury

Han

Zou

et al. 2016

Human Gene Therapy

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Mesenchymal stem cells (MSCs) represent a promising approach for the treatment of acute respiratory distress syndrome (ARDS). However, their low efficiency in homing to injured lung tissue limits their therapeutic effect. Prostaglandin E2 (PGE2) biosynthesis substantially enhances the inflammatory response of the tissue. Moreover, it also facilitates the migration of MSCs by activating the E-prostanoid 2 (EP2) receptor in vitro. Given these observations, it would seem reasonable that PGE2 might act as a chemokine to promote the migration of MSCs through activation of the EP2 receptor. Herein, we confirmed that PGE2 was significantly increased in lung tissue as a result of stimulation by LPS. In addition, we constructed a lentiviral vector carrying the EP2 gene, which was successfully transduced into MSCs (MSCs-EP2). Near-infrared imaging and immunofluorescence showed that compared with MSCs-GFP, MSCs-EP2 significantly enhanced MSC homing to injured lung tissue. Moreover, the diminished amounts of Evans blue in homogeneous lung parenchyma in vivo indicated, in comparison with MSCs-GFP, that MSCs-EP2 significantly decreased LPS-induced pulmonary vascular permeability. In addition, administration of MSCs-EP2 largely decreased the levels of interleukin-1β and tumor necrosis factor-α compared with that observed after administration of MSCs-GFP at both 24 and 72 hr. Our results suggested that treatment with MSCs-EP2 markedly enhanced MSC homing to damaged lung tissue and, in addition, improved both lung inflammation and permeability. Thus, MSCs and EP2 combination gene therapy could markedly facilitate MSC homing to areas of inflammation, representing a novel strategy for MSC-based gene therapy in inflammatory diseases.

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“…This migration and homing potential without tumorigenic potential has been described in different disease [41,42] and in BPD models previously [38,43]. Chemokines with chemokine receptors CXCR3, CXCR4 and CXCR6 were identified as the key players responsible for cell homing [44]. Further, CXCR4 ligands such as stromal cell-derived factor-1a (SDF-1a) promote MSCs' migration to the injury site [45].…”

Section: Mscs and Bpdmentioning

confidence: 94%

Stem cells and Bronchopulmonary Dysplasia - The five questions: Which cells, when, in which dose, to which patients via which route?

Mueller

Kramer

2017

Paediatric Respiratory Reviews

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CXCR4 Receptor Overexpression in Mesenchymal Stem Cells Facilitates Treatment of Acute Lung Injury in Rats

Cited by 130 publications

References 52 publications

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy

E-Prostanoid 2 Receptor Overexpression Promotes Mesenchymal Stem Cell Attenuated Lung Injury

Stem cells and Bronchopulmonary Dysplasia - The five questions: Which cells, when, in which dose, to which patients via which route?

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