CXCR4 or CXCR7 antagonists treat endometriosis by reducing bone marrow cell trafficking.
Adult Stem Cells
/ drug effects
Animals
Benzylamines
/ pharmacology
Bone Marrow Cells
/ drug effects
Bone Marrow Transplantation
/ methods
Cell Movement
/ drug effects
Cyclams
/ pharmacology
Endometriosis
/ drug therapy
Endometrium
/ drug effects
Female
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, CXCR
/ antagonists & inhibitors
Receptors, CXCR4
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Uterus
/ drug effects
AMD3100
BMDSC
CCX771
CXCR4
CXCR7
bone marrow-derived stem cells
endometriosis
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
17
07
2019
revised:
29
10
2019
accepted:
25
11
2019
pubmed:
7
1
2020
medline:
28
4
2021
entrez:
7
1
2020
Statut:
ppublish
Résumé
Adult stem cells have a major role in endometrial physiology, including remodelling and repair. However, they also have a critical role in the development and progression of endometriosis. Bone marrow-derived stem cells engraft eutopic endometrium and endometriotic lesions, differentiating to both stromal and epithelial cell fates. Using a mouse bone marrow transplantation model, we show that bone marrow-derived cells engrafting endometriosis express CXCR4 and CXCR7. Targeting either receptor by the administration of small molecule receptor antagonists AMD3100 or CCX771, respectively, reduced BM-derived stem cell recruitment into endometriosis implants. Endometriosis lesion size was decreased compared to vehicle controls after treatment with each antagonist in both an early growth and established lesion treatment model. Endometriosis lesion size was not effected when the local effects of CXCL12 were abrogated using uterine-specific CXCL12 null mice, suggesting an effect primarily on bone marrow cell migration rather than a direct endometrial effect. Antagonist treatment also decreased hallmarks of endometriosis physiopathology such as pro-inflammatory cytokine production and vascularization. CXCR4 and CXCR7 antagonists are potential novel, non-hormonal therapies for endometriosis.
Identifiants
pubmed: 31904910
doi: 10.1111/jcmm.14933
pmc: PMC7028867
doi:
Substances chimiques
ACKR3 protein, human
0
Benzylamines
0
CXCR4 protein, human
0
Cyclams
0
Receptors, CXCR
0
Receptors, CXCR4
0
plerixafor
S915P5499N
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2464-2474Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD076422
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD052668
Pays : United States
Organisme : NIH HHS
ID : R01 HD076422
Pays : United States
Organisme : NIH HHS
ID : NIH U54 HD052668
Pays : United States
Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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