The Latest Developments in Immunomodulation of Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions, Both Allogeneic and Autologous

Chen, Jia-ming; Huang, Qiao-yi; Zhao, Yunxia; Chen, Weihong; Lin, Shu; Shi, Qi-yang

doi:10.3389/fimmu.2021.785717

Cited by 19 publications

(12 citation statements)

References 136 publications

(165 reference statements)

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“…Another suggestion is that widespread apoptosis of transplanted cells occurs in the host’s circulation or the recipient’s microenvironment during transplantation [ 23 ]. Despite their low immunogenicity, hADSCs can still be recognized and eliminated by the potent immune systems of recipient cells due to allogeneic transplantation [ 42 – 44 ]. The Fas ligand (FASL)-FAS pathway has been regarded as a highly correlated route of inducing immune rejection, thereby mediating the apoptosis of transplanted stem cells [ 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

TNF-α/IL-1β-licensed hADSCs alleviate cholestatic liver injury and fibrosis in mice via COX-2/PGE2 pathway

Luan

Chen

et al. 2023

Stem Cell Res Ther

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Background Adipose tissue-derived stem cell (ADSC) transplantation has been shown to be effective for the management of severe liver disorders. Preactivation of ADSCs enhanced their therapeutic efficacy. However, these effects have not yet been examined in relation to cholestatic liver injury. Methods In the present study, a cholestatic liver injury model was established by bile duct ligation (BDL) in male C57BL/6 mice. Human ADSCs (hADSCs) with or without tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) pretreatment were administrated into the mice via tail vein injections. The efficacy of hADSCs on BDL-induced liver injury was assessed by histological staining, real-time quantitative PCR (RT-qPCR), Western blot, and enzyme-linked immune sorbent assay (ELISA). In vitro, the effects of hADSC conditioned medium on the activation of hepatic stellate cells (HSCs) were investigated. Small interfering RNA (siRNA) was used to knock down cyclooxygenase-2 (COX-2) in hADSCs. Results TNF-α/IL-1β preconditioning could downregulate immunogenic gene expression and enhance the engraftment efficiency of hADSCs. Compared to control hADSCs (C-hADSCs), TNF-α/IL-1β-pretreated hADSCs (P-hADSCs) significantly alleviated BDL-induced liver injury, as demonstrated by reduced hepatic cell death, attenuated infiltration of Ly6G + neutrophils, and decreased expression of pro-inflammatory cytokines TNF-α, IL-1β, C-X-C motif chemokine ligand 1 (CXCL1), and C-X-C motif chemokine ligand 2 (CXCL2). Moreover, P-hADSCs significantly delayed the development of BDL-induced liver fibrosis. In vitro, conditioned medium from P-hADSCs significantly inhibited HSC activation compared to that from C-hADSCs. Mechanistically, TNF-α/IL-1β upregulated COX-2 expression and increased prostaglandin E2 (PGE2) secretion. The blockage of COX-2 by siRNA transfection reversed the benefits of P-hADSCs for PGE2 production, HSC activation, and liver fibrosis progression. Conclusion In conclusion, our results suggest that TNF-α/IL-1β pretreatment enhances the efficacy of hADSCs in mice with cholestatic liver injury, partially through the COX-2/PGE2 pathway.

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Section: Discussionmentioning

confidence: 99%

TNF-α/IL-1β-licensed hADSCs alleviate cholestatic liver injury and fibrosis in mice via COX-2/PGE2 pathway

Luan

Chen

et al. 2023

Stem Cell Res Ther

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“…Although MSCs express only a limited level of MHC class I and lack MHC class II and its cofactors ( Samadi et al, 2021 ; J. Chen J-m et al, 2021 ), inflammatory reactions, graft rejection, and the development of graft-versus-host disease have been reported in animal models ( Poncelet et al, 2007 ; Pezzanite et al, 2015 ; Owens et al, 2016 ). The choices between autologous versus allogenic cells often depend on the disease background, availability of cells (and donors), cost and window of delivery.…”

Section: Discussionmentioning

confidence: 99%

“Adipose-derived mesenchymal stem cell therapy for the management of female sexual dysfunction: Literature reviews and study design of a clinical trial”

Hoang

Nguyen

Hoang

et al. 2022

Front. Cell Dev. Biol.

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Hormone imbalance and female sexual dysfunction immensely affect perimenopausal female health and quality of life. Hormone therapy can improve female hormone deficiency, but long-term use increases the risk of cardiovascular diseases and cancer. Therefore, it is necessary to develop a novel effective treatment to achieve long-term improvement in female general and sexual health. This study reviewed factors affecting syndromes of female sexual dysfunction and its current therapy options. Next, the authors introduced research data on mesenchymal stromal cell/mesenchymal stem cell (MSC) therapy to treat female reproductive diseases, including Asherman’s syndrome, premature ovarian failure/primary ovarian insufficiency, and vaginal atrophy. Among adult tissue-derived MSCs, adipose tissue-derived stem cells (ASCs) have emerged as the most potent therapeutic cell therapy due to their abundant presence in the stromal vascular fraction of fat, high proliferation capacity, superior immunomodulation, and strong secretion profile of regenerative factors. Potential mechanisms and side effects of ASCs for the treatment of female sexual dysfunction will be discussed. Our phase I clinical trial has demonstrated the safety of autologous ASC therapy for women and men with sexual hormone deficiency. We designed the first randomized controlled crossover phase II trial to investigate the safety and efficacy of autologous ASCs to treat female sexual dysfunction in perimenopausal women. Here, we introduce the rationale, trial design, and methodology of this clinical study. Because aging and metabolic diseases negatively impact the bioactivity of adult-derived MSCs, this study will use ASCs cultured in physiological oxygen tension (5%) to cope with these challenges. A total of 130 perimenopausal women with sexual dysfunction will receive two intravenous infusions of autologous ASCs in a crossover design. The aims of the proposed study are to evaluate 1) the safety of cell infusion based on the frequency and severity of adverse events/serious adverse events during infusion and follow-up and 2) improvements in female sexual function assessed by the Female Sexual Function Index (FSFI), the Utian Quality of Life Scale (UQOL), and the levels of follicle-stimulating hormone (FSH) and estradiol. In addition, cellular aging biomarkers, including plasminogen activator inhibitor-1 (PAI-1), p16 and p21 expression in T cells and the inflammatory cytokine profile, will also be characterized. Overall, this study will provide essential insights into the effects and potential mechanisms of ASC therapy for perimenopausal women with sexual dysfunction. It also suggests direction and design strategies for future research.

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“…Therefore, how to regenerate the damaged endometrium and restore its function is an important problem and great challenge for IUA treatment. Recently, cell therapy for IUA is promising in the treatment of endometrial dysfunction [14]. Mesenchymal stem cells (MSCs) are considered to be an ideal cell type for tissue regeneration due to their high potential differentiation, self-renewal and immune regulation [15].…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium

Hua

Zhang

et al. 2022

Stem Cell Res Ther

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Purpose The fundamental cause of intrauterine adhesions (IUAs) is the destruction and reduction in stem cells in endometrial basal layer, resulting in endometrial reconstruction very difficult. The purpose of this study was to investigate the effects and underlying mechanism of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on the endometrial reconstruction after transplantation. Methods hUCB-MSCs were isolated and identified by flow cytometry, osteogenic, adipogenic and chondrogenic differentiation assays. The rabbit IUA models were established and set five groups (control, 14/28th day after surgery, estrogen and hUCB-MSCs treatment). The number of endometrial glands and the fibrosis rate were evaluated using HE and Masson staining, respectively. Endometrial proliferation, angiogenesis and inflammation were evaluated by immunohistochemical staining of ER, Ki-67and TGF-β1, respectively. Single-cell RNA sequencing (scRNA-seq) was applied to explore the cell differentiation trajectory after hUCB-MSCs transplanted into IUA endometrium. Finally, molecular mechanism of hUCB-MSCs repairing damaged endometrium was investigated by RNA sequencing, qRT-PCR and Western blot assays. Results After transplantation of the hUCB-MSCs, the increase in endometrial gland number, estrogen receptor (ER) and Ki-67 expression, and the decrease in fibrosis rate and TGF-β expression (P < 0.05), suggested the endometrial repair, angiogenesis and inflammatory suppression. The therapeutic effect of hUCB-MSCs was significantly improved compared with 28th day after surgery and estrogen group. ScRNA-seq demonstrated that the transplanted hUCB-MSCs can trans-differentiate into endometrial cells: epithelial, fibroblast and macrophage. RNA sequencing of six IUA samples combined with qRT-PCR and Western blot assays further revealed that hUCB-MSCs may regulate Th17/Treg balance through NF-κB signaling, thus inhibiting the immune response of damaged endometrium. Conclusions Our study demonstrated that hUCB-MSCs can repair damaged endometrium through trans-differentiation, immunomodulatory capacities and NF-κB signaling, suggesting the treatment value of hUCB-MSCs in IUA.

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The Latest Developments in Immunomodulation of Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions, Both Allogeneic and Autologous

Cited by 19 publications

References 136 publications

TNF-α/IL-1β-licensed hADSCs alleviate cholestatic liver injury and fibrosis in mice via COX-2/PGE2 pathway

TNF-α/IL-1β-licensed hADSCs alleviate cholestatic liver injury and fibrosis in mice via COX-2/PGE2 pathway

“Adipose-derived mesenchymal stem cell therapy for the management of female sexual dysfunction: Literature reviews and study design of a clinical trial”

Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium

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