Mesenchymal Stem/Stromal Cells Overexpressing CXCR4R334X Revealed Enhanced Migration: A Lesson Learned from the Pathogenesis of WHIM Syndrome

C-X-C chemokine receptor type 4 (CXCR4), initially recognized as a co-receptor for HIV, contributes to several disorders, including the WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome. CXCR4 binds to its ligand SDF-1 to make an axis involved in the homing property of stem...

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Bibliographic Details
Published in:Cell transplantation 2021-11, Vol.30, p.9636897211054498-9636897211054498
Main Authors: Bidkhori, Hamid Reza, Bahrami, Ahmad Reza, Farshchian, Moein, Heirani-tabasi, Asieh, Mirahmadi, Mahdi, Hasanzadeh, Halimeh, Ahmadiankia, Naghmeh, Faridhosseini, Reza, Dastpak, Mahtab, Shabgah, Arezoo Gowhari, Matin, Maryam M.
Format: Article
Language:English
Subjects:
Chemokine receptors
Cloning vectors
CXCR4 protein
DNA sequencing
HIV
Homing behavior
Human immunodeficiency virus
Hypogammaglobulinemia
Mesenchymal stem cells
Mesenchyme
mRNA
Original
Pathogenesis
SDF-1 protein
Stem cells
Stromal cells
Warts
Western blotting
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Summary:C-X-C chemokine receptor type 4 (CXCR4), initially recognized as a co-receptor for HIV, contributes to several disorders, including the WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome. CXCR4 binds to its ligand SDF-1 to make an axis involved in the homing property of stem cells. This study aimed to employ WHIM syndrome pathogenesis as an inspirational approach to reinforce cell therapies. Wild type and WHIM-type variants of the CXCR4 gene were chemically synthesized and cloned in the pCDH-513B-1 lentiviral vector. Molecular cloning of the synthetic genes was confirmed by DNA sequencing, and expression of both types of CXCR4 at the protein level was confirmed by western blotting in HEK293T cells. Human adipose-derived mesenchymal stem cells (Ad-MSCs) were isolated, characterized, and subjected to lentiviral transduction with Wild type and WHIM-type variants of CXCR4. The presence of copGFP-positive MSCs confirmed the high efficiency of transduction. The migration ability of both groups of transduced cells was then assessed by transwell migration assay in the presence or absence of a CXCR4-blocking agent. Our qRT-PCR results showed overexpression of CXCR4 at mRNA level in both groups of transduced MSCs, and expression of WHIM-type CXCR4 was significantly higher than Wild type CXCR4 (P
ISSN:0963-6897
1555-3892
DOI:10.1177/09636897211054498