Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles to Treat PCOS

被引:26
作者
Park, Hang-Soo [1 ]
Cetin, Esra [1 ]
Siblini, Hiba [1 ]
Seok, Jin [1 ]
Alkelani, Hiba [1 ]
Alkhrait, Samar [1 ]
Liakath Ali, Farzana [1 ]
Ghasroldasht, Mohammad Mousaei [1 ]
Beckman, Analea [1 ]
Al-Hendy, Ayman [1 ]
机构
[1] Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA
关键词
mesenchymal stem cell; extracellular vesicles; exosome; polycystic ovary syndrome; intravenous injection; intraovarian injection; fertility; POLYCYSTIC-OVARY-SYNDROME; ANDROGEN PRODUCTION; INSULIN; INFLAMMATION; PREVALENCE; MECHANISMS; EXOSOMES; GAMMA;
D O I
10.3390/ijms241311151
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in women. Previously, we suggested that human mesenchymal stem cells (MSCs) can reverse the PCOS condition by secreting factors. Here, we evaluated the therapeutic capability of MSC-derived extracellular vesicles (EVs), also known as exosomes, in both in vitro and in vivo PCOS models. Exosomes were used to treat androgen-producing H293R cells and injected in a mouse model through intraovarian and intravenous injection into a letrozole (LTZ)-induced PCOS mouse model. We assessed the effects of the exosomes on androgen-producing cells or the PCOS mouse model by analyzing steroidogenic gene expression (quantitative real-time polymerase chain reaction (qRT-PCR)), body weight change, serum hormone levels, and fertility by pup delivery. Our data show the therapeutic effect of MSC-derived EVs for reversing PCOS conditions, including fertility issues. Interestingly, intravenous injection was more effective for serum glucose regulation, and an intraovarian injection was more effective for ovary restoration. Our study suggests that MSC-derived exosomes can be promising biopharmaceutics for treating PCOS conditions as a novel therapeutic option. Despite the fact that we need more validation in human patients, we may evaluate this novel treatment option for PCOS with the following clinical trials.
引用
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页数:14
相关论文
共 66 条
[51]   A critical role of IFNγ in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1 [J].
Sheng, Huiming ;
Wang, Ying ;
Jin, Yuqing ;
Zhang, Qiuyu ;
Zhang, Yan ;
Wang, Li ;
Shen, Baihua ;
Yin, Shuo ;
Liu, Wei ;
Cui, Lei ;
Li, Ningli .
CELL RESEARCH, 2008, 18 (08) :846-857
[52]  
Shibata Y, 2023, ACTA MED OKAYAMA, V77, P243, DOI 10.18926/AMO/65489
[53]   Harnessing the mesenchymal stem cell secretome for regenerative urology [J].
Sun, Daniel Z. ;
Abelson, Benjamin ;
Babbar, Paurush ;
Damaser, Margot S. .
NATURE REVIEWS UROLOGY, 2019, 16 (06) :363-375
[54]   Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome [J].
Teede, Helena J. ;
Misso, Marie L. ;
Costello, Michael F. ;
Dokras, Anuja ;
Laven, Joop ;
Moran, Lisa ;
Piltonen, Terhi ;
Norman, Robert J. .
HUMAN REPRODUCTION, 2018, 33 (09) :1602-1618
[55]   MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment [J].
Toh, Wei Seong ;
Lai, Ruenn Chai ;
Hui, James Hoi Po ;
Lim, Sai Kiang .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2017, 67 :56-64
[56]   In Vitro Inhibitory Effect of Mesenchymal Stem Cells on Zymosan-Induced Production of Reactive Oxygen Species [J].
Tsyb, A. F. ;
Petrov, V. N. ;
Konoplyannikov, A. G. ;
Saypina, E. V. ;
Lepechina, L. A. ;
Kalsina, S. Sh. ;
Semenkova, I. V. ;
Agaeva, E. V. .
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE, 2008, 146 (01) :158-164
[57]   Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement [J].
Ullah, Mujib ;
Liu, Daniel D. ;
Thakor, Avnesh S. .
ISCIENCE, 2019, 15 :421-438
[58]   Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine [J].
Vizoso, Francisco J. ;
Eiro, Noemi ;
Cid, Sandra ;
Schneider, Jose ;
Perez-Fernandez, Roman .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (09)
[59]   Mesenchymal Stem Cells Alleviate DHEA-Induced Polycystic Ovary Syndrome (PCOS) by Inhibiting Inflammation in Mice [J].
Xie, Qi ;
Xiong, XingLiang ;
Xiao, Na ;
He, Ke ;
Chen, Maosheng ;
Peng, Jing ;
Su, Xian ;
Mei, Hua ;
Dai, Yanni ;
Wei, Dan ;
Lin, Ge ;
Cheng, Lamei .
STEM CELLS INTERNATIONAL, 2019, 2019
[60]   Calcium carbonate nanoparticles tumor delivery for combined chemo-photodynamic therapy: Comparison of local and systemic administration [J].
Yakubova, Anastasiya A. ;
Mitusova, Ksenia A. ;
Darwish, Aya ;
Rogova, Anna ;
Ageev, Eduard I. ;
Brodskaia, Aleksandra ;
Muslimov, Albert R. ;
Zyuzin, Mikhail, V ;
Timin, Alexander S. .
JOURNAL OF CONTROLLED RELEASE, 2023, 359 :400-414