Review
Pharmacology & Pharmacy
Mahin Izadi, Mohammad Ebrahim Rezvani, Ali Aliabadi, Mahdieh Karimi, Behrouz Aflatoonian
Summary: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and the prevalence varies. Studies suggest that exosomes derived from mesenchymal stem cells may have therapeutic effects on PCOS by regulating immune response, reducing inflammation, and inhibiting granulosa cell apoptosis.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Endocrinology & Metabolism
Zhiqi Liao, Chang Liu, Lan Wang, Cong Sui, Hanwang Zhang
Summary: Reproductive disorders such as intrauterine adhesion, premature ovarian insufficiency, and polycystic ovary syndrome pose significant threats to female reproduction, but mesenchymal stem cells derived-extracellular vesicles have shown potentials in treating these diseases through various mechanisms.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jimin Kim, Seon-Yeong Jeong, Sang-Deok Han, Somi Park, Soo Kim, Tae Min Kim
Summary: This study investigates the potential of induced mesenchymal stem cell-derived extracellular vesicles (iMSC-EVs) in regulating AMPK signaling and lipid metabolism. The findings suggest that iMSC-EVs can inhibit free fatty acid release, improve hepatic steatosis, reduce fatty acid transport to the liver, and alleviate inflammation, endoplasmic reticulum stress, and apoptosis in NASH. iMSC-EVs show promise as cell-free therapeutics for NASH.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Peripheral Vascular Disease
Fabrizio Buffolo, Silvia Monticone, Giovanni Camussi, Elena Aikawa
Summary: Extracellular vesicles (EVs) are membrane-bound structures released by cells that play a pathological role in vascular damage. They facilitate cell-to-cell communication by transferring nucleic acids, protein cargos, and metabolites. EVs promote endothelial dysfunction, vascular inflammation, and contribute to plaque formation and vascular calcification.
Article
Cell Biology
Gina D. Kusuma, Anqi Li, Dandan Zhu, Hannah McDonald, Ishmael M. Inocencio, Daniel C. Chambers, Kenneth Sinclair, Haoyun Fang, David W. Greening, Jessica E. Frith, Rebecca Lim
Summary: The impact of 3D culture on the secretion, proteome composition, and functional properties of extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) was evaluated in this study. The results showed that EVs from 3D culture did not enhance typical MSC-EV properties expected from 2D culture, such as immunomodulation, anti-fibrotic, and anti-inflammatory effects. The study highlighted the critical differences between MSC-EVs obtained from different culture microenvironments, which should be considered in clinical manufacturing.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biology
Gi Beom Kim, Oog-Jin Shon, Min-Soo Seo, Young Choi, Wook Tae Park, Gun Woo Lee
Summary: Although conventional MSC-based therapies have limitations, MSC-derived exosomes offer advantages such as small dimensions, low immunogenicity, and potent therapeutic effects for osteoarthritis treatment. Exosomes are nano-sized vesicles containing nucleic acids, functional proteins, and bioactive lipids, secreted by various cell types. They play a role in tissue repair, immune regulation, and inflammation reduction, demonstrating potential for a new therapeutic approach in osteoarthritis. Further research is needed to confirm their clinical effectiveness and feasibility.
Review
Cell & Tissue Engineering
Zahra Moayedfard, Farnaz Sani, Aliakbar Alizadeh, Kamran Bagheri Lankarani, Mohammad Zarei, Negar Azarpira
Summary: Non-Alcoholic Fatty Liver Disease (NAFLD) is a disease characterized by triglyceride accumulation in liver cells and involvement of the immune system. Various molecular pathways, including lipotoxicity, endoplasmic reticulum stress, and the immune response, are involved in the progression of NAFLD. Both innate and adaptive immune systems play important roles in the pathogenesis of NAFLD.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Immunology
Claire Loussouarn, Yves-Marie Pers, Claire Bony, Christian Jorgensen, Daniele Noel
Summary: MSCs stimulate tissue repair by releasing EVs, which contain various molecules including miRNAs. These EVs impact the metabolism and oxidative stress of target cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Kelin Zhao, Chenfei Kong, Naixu Shi, Jinlan Jiang, Ping Li
Summary: This review summarizes the therapeutic effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) on systemic sclerosis (SSc) and the mechanisms, providing a theoretical basis for future research on the role of MSC-EVs in treating SSc.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Mohammad A. Gholampour, Saeid Abroun, Rienk Nieuwland, Seyed J. Mowla, Sara Soudi
Summary: The study showed that treatment with hypoxic MSC-EVs and normoxic MSC-EVs significantly prolonged the survival rate, increased platelet counts, and ameliorated BM hypoplasia in a mouse model of AA. The effects of MSC-EVs were mediated by T cell suppression and inhibition of interferon-gamma and tumor necrosis factor-alpha production. Additionally, there was an association between reduced pro-inflammatory cytokine levels and decreased splenocyte viability in vitro.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Soo-Eun Sung, Kyung-Ku Kang, Joo-Hee Choi, Si-Joon Lee, KilSoo Kim, Ju-Hyeon Lim, Seung Yun Yang, Seul-Ki Kim, Min-Soo Seo, Gun Woo Lee
Summary: Extracellular vesicles (EVs) are membrane-bound particles secreted by cells, and stem cell-derived EVs have been shown to have therapeutic effects similar to stem cells. This study isolated EVs from human epidural fat-derived mesenchymal stem cells and human fibroblasts, and found that EVs from the MSCs exhibited stronger anti-inflammatory effects compared to those from fibroblasts. The results suggest that EVs from human epidural fat MSCs may be valuable for treating inflammation-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Zhijie Weng, Bowen Zhang, Chenzhou Wu, Fanyuan Yu, Bo Han, Bo Li, Longjiang Li
Summary: Extracellular vesicles (EVs) are essential regulators of intercellular communication enclosing various biomolecules, and MSC-derived EVs have shown potential applications in cancer treatment. However, challenges remain in translating MSC-derived EVs from bench to bedside.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Yiming Ma, Xiangming Liu, Yingjiao Long, Yan Chen
Summary: This review summarizes the strategies and mechanisms of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in treating chronic respiratory diseases. MSC-EVs may serve as a novel cell-free therapy for these diseases by transferring microRNAs and proteins to target cells.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Medicine, General & Internal
Yu Ning, Peisen Huang, Guihao Chen, Yuyan Xiong, Zhaoting Gong, Chunxiao Wu, Junyan Xu, Wenyang Jiang, Xiaosong Li, Ruijie Tang, Lili Zhang, Mengjin Hu, Jing Xu, Jun Xu, Haiyan Qian, Chen Jin, Yuejin Yang
Summary: This study found that MSCATV-EV, derived from ATV-treated MSCs, has a good cardiac repair effect on acute myocardial infarction. The results showed that MSCATV-EV alleviated inflammation in the infarct region by regulating macrophage polarization. Additionally, the study identified the miR-139-3p/Stat1 pathway as the mechanism underlying the promotion of macrophage polarization by MSCATV-EV.
Article
Engineering, Biomedical
Wenkai Jia, Weilue He, Guifang Wang, Jeremy Goldman, Feng Zhao
Summary: This study found that ECM secreted by hMSCs enhances lymphangiogenesis and has the potential for treating lymphedema.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Cardiac & Cardiovascular Systems
Takahito Doi, Mika Hori, Mariko Harada-Shiba, Yu Kataoka, Daisuke Onozuka, Kunihiro Nishimura, Ryo Nishikawa, Kosuke Tsuda, Masatsune Ogura, Cheol Son, Yoshihiro Miyamoto, Teruo Noguchi, Hiroaki Shimokawa, Satoshi Yasuda
Summary: Patients with both LDLR and PCSK9 gene variants have higher levels of LDL cholesterol and increased risk of cardiovascular events, particularly nonfatal myocardial infarction. These patients require more intensive antiatherosclerotic management.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Urology & Nephrology
Takeo Ishii, Masatsune Ogura, Haruka Nakamori, Mika Hori, Mariko Harada-Shiba, Kouichi Tamura, Kunio Oyama
Summary: The combination of FH and ESRD can lead to an increased risk of ASCVD, requiring alternative treatment options such as PCSK9 inhibitors in some cases. In this case report, two siblings with FH and ESRD were successfully treated with PCSK9 inhibitors, resulting in significant reduction of LDL-C levels.
Editorial Material
Medicine, General & Internal
Hiroshi Yoshida, Yuji Hirowatari, Masatsune Ogura, Mariko Harada-Shiba
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Peripheral Vascular Disease
Masahito Michikura, Masatsune Ogura, Mika Hori, Kota Matsuki, Hisashi Makino, Kiminori Hosoda, Mariko Harada-Shiba
Summary: This study aimed to investigate the association between AT softness and carotid atherosclerosis and ASCVD in FH patients. The results showed that AT softness was associated with age and inversely correlated with overweight. In FH patients, there were significant inverse correlations between AT softness and maximum and mean IMT within the common carotid artery.
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
(2022)
Article
Pharmacology & Pharmacy
Mika Hori, Atsushi Takahashi, Kiminori Hosoda, Mariko Harada-Shiba
Summary: In this study, a novel exon2_6dup variant was identified in the LDLR gene through whole-genome sequencing. The variant was found to be associated with nonallelic homologous recombination with Alu sequences.
JOURNAL OF CLINICAL LIPIDOLOGY
(2022)
Article
Peripheral Vascular Disease
Ryo Nishikawa, Masato Furuhashi, Mika Hori, Masatsune Ogura, Mariko Harada-Shiba, Takeshi Okada, Masahiro Koseki, Takeshi Kujiraoka, Hiroaki Hattori, Ryosuke Ito, Atsuko Muranaka, Nobuaki Kokubu, Tetsuji Miura
Summary: This case report describes the first case of a heterozygous FH phenotype caused by possibly oligogenic variants of the PCSK9 and ABCG5 genes complicated with type I CD36 deficiency caused by a novel homozygous mutation. Both FH phenotype and CD36 deficiency might have caused extensive atherosclerosis, leading to acute myocardial infarction.
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
(2022)
Article
Peripheral Vascular Disease
Hayato Tada, Mika Hori, Kota Matsuki, Masatsune Ogura, Atsushi Nohara, Masa-aki Kawashiri, Mariko Harada-Shiba
Summary: The study aimed to determine a new cut-off value of Achilles tendon thickness (ATT) detected by X-ray to differentiate between familial hypercholesterolemia (FH) and non-FH based on genetic diagnosis. The results showed that the best cut-off values for male and female were 7.6 mm and 7.0 mm, respectively, improving the prediction of FH pathogenic mutation.
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
(2022)
Article
Cardiac & Cardiovascular Systems
Sayaka Funabashi, Yu Kataoka, Mika Hori, Masatsune Ogura, Takahito Doi, Teruo Noguchi, Mariko Harada-Shiba
Summary: The study found that elevated Lp(a) levels in HeFH patients predicted the occurrence of polyVD. This suggests that patients with HeFH and Lp(a) >= 50 mg/dL are at high risk and require meticulous screening of systemic vascular beds.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Cardiac & Cardiovascular Systems
Masahito Michikura, Mika Hori, Masatsune Ogura, Kiminori Hosoda, Mariko Harada-Shiba
Summary: This study found a significant correlation between LDLR gene variants and AT thickness and softness, while PCSK9 gene variants were not associated. Evaluating AT is important for identifying FH patients with LDLR gene variants at high risk for CAD.
Article
Endocrinology & Metabolism
Mika Hori, Atsushi Takahashi, Kiminori Hosoda, Masatsune Ogura, Mariko Harada-Shiba
Summary: Whole-exome sequencing was performed on 122 families with familial hypercholesterolemia (FH) and no pathogenic variants were found. However, a high frequency of the APOB c.2863C > T:p.(Pro955Ser) variant was identified. This variant has a moderate effect on the risk of FH.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Peripheral Vascular Disease
Kota Matsuki, Mariko Harada-Shiba, Mika Hori, Masatsune Ogura, Yusuke Akiyama, Hisako Fujii, Yutaka Ishibashi, Tatsuro Ishida, Yasushi Ishigaki, Daijiro Kabata, Yasuki Kihara, Kazuhiko Kotani, Satoshi Kurisu, Daisaku Masuda, Tetsuya Matoba, Takeshi Matsumura, Kenta Mori, Tomoko Nakagami, Masamitsu Nakazato, Satsuki Taniuchi, Hiroaki Ueno, Shizuya Yamashita, Hiroshi Yoshida, Hisako Yoshida, Tetsuo Shoji
Summary: This study aimed to compare the differences in serum markers of cholesterol metabolism between familial hypercholesterolemia (FH) and non-FH individuals and examine their associations with serum lipid levels. The FH group showed significantly elevated serum concentrations of campesterol (Campe) and sitosterol (Sito) and insignificantly elevated concentrations of lathosterol (Latho) compared to the non-FH group. These findings suggest that intestinal cholesterol absorption relative to hepatic cholesterol synthesis is elevated in patients with FH. Serum lathosterol, campesterol, and sitosterol concentrations showed nonlinear associations with total cholesterol (TC) in the FH group.
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
(2023)
Article
Peripheral Vascular Disease
Mika Hori, Yukiko Hasegawa, Yoshitaka Hayashi, Tomoko Nakagami, Mariko Harada-Shiba
Summary: We investigated the effect of GLP-1 receptor agonist exendin-4 on serum LDL-C levels and its mechanism in Ldlr-/- and C57BL/6J mice. The treatment decreased serum VLDL-C and LDL-C levels in both mouse strains, independent of LDLR.
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
(2023)
Review
Cardiac & Cardiovascular Systems
Marina Cuchel, Frederick J. Raal, Robert A. Hegele, Khalid Al-Rasadi, Marcello Arca, Maurizio Averna, Eric Bruckert, Tomas Freiberger, Daniel Gaudet, Mariko Harada-Shiba, Lisa C. Hudgins, Meral Kayikcioglu, Luis Masana, Klaus G. Parhofer, Jeanine E. Roeters van Lennep, Raul D. Santos, Erik S. G. Stroes, Gerald F. Watts, Albert Wiegman, Jane K. Stock, Lale S. Tokgoezoglu, Alberico L. Catapano, Kausik K. Ray
Summary: This 2023 statement provides updated clinical guidance for the management of homozygous familial hypercholesterolaemia (HoFH), including criteria for diagnosis, genetic testing interpretation, and treatment recommendations. The statement emphasizes the importance of considering both phenotype and genotype in the diagnosis of HoFH, with a LDL-C level >10 mmol/L (>400 mg/dL) being indicative of the condition. Combination therapy targeting LDL-C, including the use of novel therapies like proprotein convertase subtilisin/kexin type 9 inhibitors, is recommended to achieve LDL-C goals and reduce the need for lipoprotein apheresis. To improve HoFH care globally, the statement recommends the implementation of national screening programs, education to increase awareness, and management guidelines adapted to local healthcare systems.
EUROPEAN HEART JOURNAL
(2023)
Article
Multidisciplinary Sciences
Chisato Terada, Kaho Oh, Ryutaro Tsubaki, Bun Chan, Nozomi Aibara, Kaname Ohyama, Masa-Aki Shibata, Takehiko Wada, Mariko Harada-Shiba, Asako Yamayoshi, Tsuyoshi Yamamoto
Summary: In this study, a toehold-bearing ASO architecture is developed to mitigate a broad spectrum of off-target interactions, significantly enhancing the safety profile of ASO drugs.
NATURE COMMUNICATIONS
(2023)