scholarly journals Transplantation of adipose-derived stem cells combined with collagen scaffolds restores ovarian function in a rat model of premature ovarian insufficiency

2016 ◽  
Vol 31 (5) ◽  
pp. 1075-1086 ◽  
Author(s):  
Jing Su ◽  
Lijun Ding ◽  
Jie Cheng ◽  
Jun Yang ◽  
Xin'an Li ◽  
...  
2021 ◽  
Vol 76 (2) ◽  
pp. 35-40
Author(s):  
M. I. Kozub ◽  
K. P. Skybina ◽  
I. B. Musatova ◽  
O. V. Prokopiuk ◽  
S. M. Gramatiuk ◽  
...  

Premature ovarian insufficiency (POI) is condition of female hypogonadism. One of the reasons for the development of POI is anticancer chemotherapy. Currently, hormone replacement therapy is considered the most effective method of treatment POI, which, however, had a number of side effects, requires constant administration of pharmaceuticals, did not restore fertility and correct pathological changes in target organs. Therefore, the search for alternative methods of treatment based on the use of stem cells is promising. The aim of work was to compare the therapeutic effects of different methods of administration of mesenchymal stem cells isolated from adipose tissue (AT MSCs) in restoring sexual function, as well as the behavior of mice with chemotherapy-induced premature ovarian failure. Materials and methods. The investigation was carried out on BALB/c mice with a POI model induced by Cyclophosphamide and Busulfan. A histological examination of preparations of the ovaries and uterus was carried out. We studied the changes in the weight of mice, ovarian function, sexual activity, as well as the behavior of animals in anxiolytic and zoosocial tests after treatment with AT MSCs with intraperitoneal and intraovarian routes of administration. Results and discussion. It was shown that the effectiveness of the use of AT MSCs depends on the method of their administration at the treatment of POI induced by chemotherapy. More rapid and complete restoration of the morphological structure, sexual function, and behavioral responses were observed in mice with POI treated by intraovarial administration of AT MSCs.  


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan Zhao ◽  
Jiao Ma ◽  
Peiye Yi ◽  
Jun Wu ◽  
Feiyan Zhao ◽  
...  

Abstract Background Premature ovarian insufficiency (POI) is an ovarian dysfunction that seriously affects a woman’s physiological health and reproduction. Mesenchymal stem cell (MSC) transplantation offers a promising treatment option for ovarian restoration in rodent POI models. However, the efficacy and mechanism of it remain unclear. Methods POI mice model was generated by cyclophosphamide and busulfan, followed with the treatment of tail-vein injection of the human umbilical cord mesenchymal stem cells (hUCMSCs). Maternal physiological changes and offspring behavior were detected. To reveal the pathogenesis and therapeutic mechanisms of POI, we first compared the metabolite profiles of healthy and POI ovarian tissues using untargeted metabolomics analyses. After stem cell therapy, we then collected the ovaries from control, POI, and hUCMSC-treated POI groups for lipid metabolomics and pseudotargeted metabolomics analysis. Results Our results revealed remarkable changes of multiple metabolites, especially lipids, in ovarian tissues after POI generation. Following the transplantation of clinical-grade hUCMSCs, POI mice exhibited significant improvements in body weight, sex hormone levels, estrous cycles, and reproductive capacity. Lipid metabolomics and pseudotargeted metabolomics analyses for the ovaries showed that the metabolite levels in the POI group, mainly lipids, glycerophospholipids, steroids, and amino acids changed significantly compared with the controls’, and most of them returned to near-healthy levels after receiving hUCMSC treatment. Meanwhile, we also observed an increase of monosaccharide levels in the ovaries from POI mice and a decrease after stem cell treatment. Conclusions hUCMSCs restore ovarian function through activating the PI3K pathway by promoting the level of free amino acids, consequently improving lipid metabolism and reducing the concentration of monosaccharides. These findings provide potential targets for the clinical diagnosis and treatment of POI.


2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Gayathri Subramanian ◽  
Alexander Stasuk ◽  
Mostafa Elsaadany ◽  
Eda Yildirim-Ayan

Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.


2021 ◽  
Vol 267 ◽  
pp. 458-466
Author(s):  
Dana McCloskey ◽  
Kimberly Linden ◽  
Andrew Lin ◽  
Ping Zhang ◽  
Jennifer Schweinsburg ◽  
...  

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