CXCR4 or CXCR7 antagonists treat endometriosis by reducing bone marrow cell trafficking

Pluchino, Nicola; Mamillapalli, Ramanaiah; Shaikh, Shafiq; Habata, Shutaro; Tal, Aya; Gaye, M; Taylor, Hugh S.

doi:10.1111/jcmm.14933

Cited by 19 publications

(7 citation statements)

References 62 publications

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“…MSCs from BM can engraft endometriosis and contribute to lesion growth. Blocking CXCR4 inhibits MSC engraftment into lesions and leads to regression of disease [29,31,32]. However, in this study, the exogenous MSCs did not engrafted the BM or lesion, rather they had a transient effect at the time of BM transplant that altered the endogenous BM.…”

Section: Discussioncontrasting

confidence: 53%

Donor Mesenchymal Stem Cells Program Bone Marrow, Altering Macrophages, and Suppressing Endometriosis in Mice

Habata

Mamillapalli

Uçar

et al. 2023

Stem Cells International

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Endometriosis is a chronic inflammatory gynecological disorder regulated by estrogen and characterized by the growth of endometrial tissue outside the uterus. We have previously demonstrated that mesenchymal stem cells (MSCs) contribute directly to endometriosis. Here, we investigated an indirect effect; we hypothesized that MSCs may also impact the bone marrow (BM) by regulating bone marrow-derived inflammatory cells. Endometriosis was induced in mice by transplanting uterine tissue into recipient mice followed by BM transplant. Control or MSC conditioned BM was injected retro-orbitally. Direct administration of MSCs outside of the setting of BM conditioning did not alter endometriosis. Coculture of an undifferentiated macrophage cell line with MSCs in vitro led to a reduction of M1 and increased M2 macrophages as determined by fluorescence-activated cell sorting and western blot. Conditioning of BM with MSCs and transplantation into a mouse model inhibited endometriotic lesion development and reduced lesion volume by sevenfold compared to BM transplant without MSCs conditioning. Immunohistochemistry and immunofluorescence showed that MSC conditioned BM reduced the infiltration of macrophages and neutrophils into endometriotic lesions by twofold and decreased the proportion of M1 compared to M2 macrophages, reducing inflammation and likely promoting tissue repair. Expression of several inflammatory markers measured by quantitative real-time polymerase chain reaction, including tumor necrosis factor alpha and CXCR4, was decreased in the conditioned BM. Donor MSCs were not detected in recipient BM or endometriotic lesions, suggesting that MSCs actively program the transplanted BM. Taken together, these data show that individual characteristics of BM have an unexpected role in the development of endometriosis. BM remodeling and alterations in the inflammatory response are also potential treatments for endometriosis. Identification of the molecular basis for BM programing by MSCs will lead to a better understanding of the immune system contribution to this disease and may lead to new therapeutic targets for endometriosis.

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Section: Discussioncontrasting

confidence: 53%

Donor Mesenchymal Stem Cells Program Bone Marrow, Altering Macrophages, and Suppressing Endometriosis in Mice

Habata

Mamillapalli

Uçar

et al. 2023

Stem Cells International

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“…347 CD24 expression has been detected in human BM-MSCs, which are regulated by TGF-β3, 348 allowing them to interact with activated endothelial cells via P-selectin and initiate the tethering and rolling steps of MSCs. 349 Additionally, BM-MSCs express high levels of CXCR4 or CXCR7, 350 , 351 which bind to integrin receptors, such as VLA-4, to activate the integrin-binding process and allow the cells to anchor to endothelial cells, followed by the migration of MSCs through the endothelial cell layer and basement membrane in a process called transmigration. 352 This process is facilitated by the secretion of matrix metalloproteinases (MMPs), which degrade the endothelial basement membrane, allowing BM-MSCs to enter the brain environment.…”

Section: Proposed Mechanism Of Bm-mscs In the Treatment Of Acquired B...mentioning

confidence: 99%

Stem cell-based therapy for human diseases

Hoang

Pham

Bach

et al. 2022

Sig Transduct Target Ther

478

138

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Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.

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“…Activation of the CXCL12/CXCR4 signaling axis promotes the ectopic lesions to outcompete eutopic endometrium to recruit the limited supply of circulating BMDSCs. Targeting CXCR4 by using the small molecule receptor antagonist AMD3100 reduces the recruitment of BMDSCs into the endometriosis and the size of the endometriosis lesions [ 147 ]. Antagonist treatment also reduces the production of pro-inflammatory cytokines and angiogenesis in the lesions of endometriosis [ 147 ].…”

Section: Stem/progenitor Cells or Stem-like Cells Of Extrauterine Origin Promote Endometriosismentioning

confidence: 99%

“…Targeting CXCR4 by using the small molecule receptor antagonist AMD3100 reduces the recruitment of BMDSCs into the endometriosis and the size of the endometriosis lesions [ 147 ]. Antagonist treatment also reduces the production of pro-inflammatory cytokines and angiogenesis in the lesions of endometriosis [ 147 ].…”

Section: Stem/progenitor Cells or Stem-like Cells Of Extrauterine Origin Promote Endometriosismentioning

confidence: 99%

Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis

et al. 2021

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Endometrial stem/progenitor cells have been proved to exist in periodically regenerated female endometrium and can be divided into three categories: endometrial epithelial stem/progenitor cells, CD140b+CD146+ or SUSD2+ endometrial mesenchymal stem cells (eMSCs), and side population cells (SPs). Endometrial stem/progenitor cells in the menstruation blood are defined as menstrual stem cells (MenSCs). Due to their abundant sources, excellent proliferation, and autotransplantation capabilities, MenSCs are ideal candidates for cell-based therapy in regenerative medicine, inflammation, and immune-related diseases. Endometrial stem/progenitor cells also participate in the occurrence and development of endometriosis by entering the pelvic cavity from retrograde menstruation and becoming overreactive under certain conditions to form new glands and stroma through clonal expansion. Additionally, the limited bone marrow mesenchymal stem cells (BMDSCs) in blood circulation can be recruited and infiltrated into the lesion sites, leading to the establishment of deep invasive endometriosis. On the other hand, cell derived from endometriosis may also enter the blood circulation to form circulating endometrial cells (CECs) with stem cell-like properties, and to migrate and implant into distant tissues. In this manuscript, by reviewing the available literature, we outlined the characteristics of endometrial stem/progenitor cells and summarized their roles in immunoregulation, regenerative medicine, and endometriosis, through which to provide some novel therapeutic strategies for reproductive and cancerous diseases.

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CXCR4 or CXCR7 antagonists treat endometriosis by reducing bone marrow cell trafficking

Cited by 19 publications

References 62 publications

Donor Mesenchymal Stem Cells Program Bone Marrow, Altering Macrophages, and Suppressing Endometriosis in Mice

Donor Mesenchymal Stem Cells Program Bone Marrow, Altering Macrophages, and Suppressing Endometriosis in Mice

Stem cell-based therapy for human diseases

Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis

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