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Series GSE122257 Query DataSets for GSE122257
Status Public on May 29, 2020
Title Topical application of hESC-derived mesenchymal stem cell spheres accelerates wound healing in a CXCL12-CXCR4 axis-dependent manner
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary It has been reported that mesenchymal stem cells (MSC) derived from adult tissues are effective in promoting wound healing. However, the cell quality varies and cell number is limited as both depend on donations. Moreover, dissociated MSC delivered to an inflammatory lesion are subject to challenges to their survival and functions. Here we demonstrate that dropping of spheres of MSC derived from human embryonic stem cells (EMSC) onto murine dermal wound had much higher survival and efficacy than topical application of dissociated EMSC. RNA sequencing on cells isolated from the wound highlights the CXCL12-CXCR4 signalling in the EMSC sphere-mediated efficacy, which was verified via CXCL12 knockdown in EMSC and CXCR4 inhibition in target cells such as vascular endothelial cells, epithelial keratinocytes, and macrophage. Finally, we enhanced the biosafety of EMSC spheres by engineering the cells with an inducible suicide gene. Together, we propose topical application of EMSC spheres as an unlimited, quality-assured, safety-enhanced, and noninvasive therapy for wound healing and the CXCL12-CXCR4 axis as a key player in the treatment.
Overall design We employed a murine model of excisional splinted skin wounds, in which contraction of skin around a wound is prevented so the wound healing effect of a treatment can be displayed and measured objectively. We directly dropped EMSCSp onto the wound surface, which promoted wound healing much faster than local delivery of EMSCDiss. EMSCSp survived longer, migrated farther, and induced more macrophage accumulation, vascular genesis and re-epithelialization in the wounds than EMSCDiss. Similar results were observed with MSC spheres derived from human bone marrow (BM-MSCSp) versus dissociated control cells. Finally, to reduce tumorigenesis concern, we transduced EMSC with a chemically inducible caspase-9 (iCasp9) and demonstrated that the engineered EMSC could be efficiently killed in vitro and eliminated in vivo post-therapy.
Contributor(s) Wang X, Jiang B, Sun H, Zheng D, Zhang Z, Yan L, Li E, Xu R
Citation(s) 31534540
Submission date Nov 07, 2018
Last update date May 30, 2020
Contact name Renhe Xu
Organization name University of Macao
Department Faculty of Health Sciences
Lab Renhe Xu lab
Street address Avenida de Universidade Taipa
City Macao
ZIP/Postal code 853
Country China
Platforms (3)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL22245 Illumina HiSeq 2500 (Homo sapiens; Mus musculus)
Samples (15)
GSM3462662 W0
GSM3462663 W D3_rep1
GSM3462664 W D3_rep2
BioProject PRJNA504412
SRA SRP168021

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Supplementary file Size Download File type/resource
GSE122257_RAW.tar 12.5 Mb (http)(custom) TAR (of XLSX)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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