Cell-free fat extract improves ovarian function and fertility in mice with premature ovarian insufficiency

Liu, Mengyu; Zhang, Dan; Zhou, Xiaowei; Duan, Jingru; Hu, Yanqin; Zhang, Wenjie; Liu, Qiang; Xu, Bufang; Zhang, Aijun

doi:10.1186/s13287-022-03012-w

Cited by 18 publications

(16 citation statements)

References 46 publications

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“…In addition, CEFFE could also enhance soft tissue regeneration and even rejuvenate aging cells. [ 11a,31 ] Given the pathophysiological commonness of these diseases, CEFFE might be an efficient therapeutic agent to delay skeletal degeneration.…”

Section: Discussionmentioning

confidence: 99%

Fat Extract Modulates Calcium Signaling and Protects against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Yang

Kan

et al. 2023

Advanced Therapeutics

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Osteoclasts are cells primarily involved in bone remodeling. Hyperactive osteoclastogenesis leads to pathological bone loss and microarchitectural deterioration. However, given the limitations of current osteoclast inhibitors, there is an urgent need for a novel antiresorptive agent with higher efficiency and fewer side effects. Cell‐free fat extract (CEFFE) is the liquid fraction obtained from adipose tissues, which are enriched with a variety of adipokines. This study aims to explore its pharmacologic effect on hyperactive osteoclastogenesis. CEFFE exhibits excellent potentials to attenuate osteoclast‐associated bone loss in ovariectomy mice and to inhibit osteoclastogenesis in primary monocytes. Furthermore, the cationic protein fraction of CEFFE (CEFFE‐Cation) is identified as the main inhibitory component in osteoclast formation assay. According to liquid chromatography with tandem mass spectrometry analysis, the CEFFE‐Cation fraction mainly consists of various antioxidant enzymes and cytokines, which endow it with a superior antioxidant capacity. Meanwhile, CEFFE‐Cation is also capable of mitigating Ca2+ oscillation and subsequent nuclear factor of activated T‐cells 1 nuclear translocation during osteoclastogenesis. Overall, this study elucidates the promising translational potential of CEFFE as a next‐generation personalized antiresorptive agent for osteolytic bone disease treatment.

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Section: Discussionmentioning

confidence: 99%

Fat Extract Modulates Calcium Signaling and Protects against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Yang

Kan

et al. 2023

Advanced Therapeutics

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“…In this study, we used a chemotherapy-induced POI mouse model with cyclophosphamide and busulfan [33,48,49]. Unlike human patients who receive chemotherapy, a few mice can still become pregnant even after chemotherapy, while most mice are infertile after chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the therapeutic effects between stem cells and exosomes in primary ovarian insufficiency

Park

Chugh

Seok

et al. 2022

Preprint

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Background: Primary ovarian insufficiency (POI) refers to the loss of ovarian function under the age of 40 and resultsin amenorrhea and infertility. Our previous studies have shown that transplantation of mesenchymal stem cells (MSCs) and MSC-derived exosomesin chemotherapy-induced POI mouse ovaries can reverse the POI and eventually achieve pregnancy. Based on our recent studies, MSC-derived exosomeshave almost equal therapeutic potentials as transplanted MSCs. However, it is still unclear whether exosomes can completely replace MSCs in POI treatment. For the reliable application of cell-free treatment for POI patients using exosomes, there is a need to understand whetherthere is any outcome and effectiveness differencebetween MSC and MSC-derived exosome treatment. Methods: Comparing the therapeutic effect of intravenous injection using MSCs and equal amountsof exosomesin aPOI mouse model will reveal the differencebetween the two therapeutic resources. In this study, we induced POI in C57/BL6 mice by chemotherapy (CXT) using a standard protocol. We then injected four different doses of MSCs or equal amountsof commercialized MSC-derived exosomesby retro-orbital injection post-CXT. Result: After MSC/exosome treatment, tissue and serum samples were harvested to analyze molecular changes after treatment,while other mice in parallel experiments underwent breeding experimentsto compare the restoration of fertility. Both the MSC- and exosome-treated groups had a restored estrous cycle and serum hormone levelscompared to untreated POI mice. The pregnancy rate in the MSC-treated group was 60% to 100% after treatment, while thepregnancy rate in the exosome-treated group was 30% to 50% after treatment. Interestingly, in terms oflong-term effects, MSC-treated mice still showed a 60% to 80% pregnancy rate in the second round of breeding, while the exosome-treated group became infertile again inthe second roundof breeding. Conclusions: Although there were some differences in the efficacy between MSC treatment and exosome treatment, both treatments were able to achieve pregnancy in the POI mouse model. In conclusion, we report that MSC-derived exosomes are apromising therapeutic option to restore ovarian function in POI conditions similar to treatment with MSCs.

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“…Each group's ovaries were randomly sampled, fixed with 4% paraformaldehyde, embedded in paraffin, and cut into 5 µm sections. Six sections from each ovary were stained with hematoxylin and eosin (H&E) for histological analysis and follicle counting [31, 32].…”

Section: Methodsmentioning

confidence: 99%

Glycyrrhizin ameliorates impaired glucose metabolism and ovarian dysfunction in a polycystic ovary syndrome mouse model

Yang

Ullah

et al. 2023

Biology of Reproduction

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Objective: The aim of this study was to determine the impact of glycyrrhizin, an inhibitor of high mobility group box 1 (HMGB1), on glucose metabolic disorders and ovarian dysfunction in mice with polycystic ovary syndrome (PCOS). Methods: We generated a PCOS mouse model by using dehydroepiandrosterone (DHEA) plus high fat diet (HFD). 100 mg/kg glycyrrhizin was intraperitoneally injected into the PCOS mice and the effects on body weight, glucose tolerance, insulin sensitivity, estrous cycle, hormone profiles, ovarian pathology, glucolipid metabolism and some molecular mechanisms were investigated. Results: Increased number of cystic follicles, hormonal disorders, impaired glucose tolerance and decreased insulin sensitivity in the PCOS mice were reverted by glycyrrhizin. The increased HMGB1 levels in the serum and ovarian tissues of the PCOS mice were also reduced by glycyrrhizin. Furthermore, increased expressions of toll-like receptor (TLR) 9, myeloid differentiation factor 88 (MyD88) and nuclear factor-κB (NF-κB) as well as reduced expressions of insulin receptor (INSR), phosphorylated protein kinase B (p-AKT) and glucose transporter type 4 (GLUT4) were restored by glycyrrhizin in the PCOS mice. Conclusions: Glycyrrhizin could suppress the PCOS-induced upregulation of HMGB1, several inflammatory marker genes and the TLR9/MyD88/NF-KB pathways, while inhibiting the INSR/p-AKT/GLUT4 pathways. Hence, glycyrrhizin is a promising therapeutic agent against PCOS.

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Cell-free fat extract improves ovarian function and fertility in mice with premature ovarian insufficiency

Cited by 18 publications

References 46 publications

Fat Extract Modulates Calcium Signaling and Protects against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Fat Extract Modulates Calcium Signaling and Protects against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Comparison of the therapeutic effects between stem cells and exosomes in primary ovarian insufficiency

Glycyrrhizin ameliorates impaired glucose metabolism and ovarian dysfunction in a polycystic ovary syndrome mouse model

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