CHARACTERIZATION OF UMBILICAL CORD TISSUE MESENCHYMAL STEM CELLS BASED ON DONOR SEX FOR PREMATURE OVARIAN INSUFFICIENCY

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.

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Exosomal miRNA-17-5p derived from human umbilical cord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7

Stem Cells ◽

10.1002/stem.3204 ◽

2020 ◽

Author(s):

Chenyue Ding ◽

Liping Zhu ◽

Han Shen ◽

Jiafeng Lu ◽

Qinyan Zou ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Ovarian Function ◽

Premature Ovarian Insufficiency ◽

Human Umbilical Cord ◽

Ovarian Insufficiency ◽

Exosomal Mirna

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Correction to: Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis

Journal of Translational Medicine ◽

10.1186/s12967-021-02869-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Neil H. Riordan ◽

Isabela Morales ◽

Giselle Fernández ◽

Nicole Allen ◽

Neal E. Fearnot ◽

...

Keyword(s):

Multiple Sclerosis ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Umbilical Cord Tissue

An amendment to this paper has been published and can be accessed via the original article.

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Heterogeneity of Umbilical Cords as a Source for Mesenchymal Stem Cells

Dataset Papers in Biology ◽

10.7167/2013/370103 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 9

Author(s):

O. O. Maslova ◽

N. S. Shuvalova ◽

O. M. Sukhorada ◽

S. M. Zhukova ◽

O. G. Deryabina ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Umbilical Cord ◽

Optimal Conditions ◽

Umbilical Cord Tissue ◽

Umbilical Cords

The object of the paper is to show the heterogeneity of 300 cord samples processed in the current research. The differences in effectiveness of mesenchymal stem cell (MSC) isolation are shown. Moreover, the recommendations for choosing the method of MSC isolation depending on the value of stromal-vascular rate are given. The data can be useful for selecting the optimal conditions to obtain MSC and for further cryopreservation of umbilical cord tissue.

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Clinical and imaging outcomes after intrathecal injection of umbilical cord tissue mesenchymal stem cells in cerebral palsy: a randomized double-blind sham-controlled clinical trial

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02513-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Man Amanat ◽

Anahita Majmaa ◽

Morteza Zarrabi ◽

Masoumeh Nouri ◽

Masood Ghahvechi Akbari ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cerebral Palsy ◽

Umbilical Cord ◽

Intrathecal Injection ◽

Control Group ◽

Umbilical Cord Tissue ◽

The Mean ◽

And Control ◽

Experimental Group

Abstract Background This study assessed the safety and efficacy of intrathecal injection of umbilical cord tissue mesenchymal stem cells (UCT-MSC) in individuals with cerebral palsy (CP). The diffusion tensor imaging (DTI) was performed to evaluate the alterations in white-matter integrity. Methods Participants (4–14 years old) with spastic CP were assigned in 1:1 ratio to receive either UCT-MSC or sham procedure. Single-dose (2 × 107) cells were administered in the experimental group. Small needle pricks to the lower back were performed in the sham-control arm. All individuals were sedated to prevent awareness. The primary endpoints were the mean changes in gross motor function measure (GMFM)-66 from baseline to 12 months after procedures. The mean changes in the modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also assessed. Secondary endpoints were the mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR). Results There were 36 participants in each group. The mean GMFM-66 scores after 12 months of intervention were significantly higher in the UCT-MSC group compared to baseline (10.65; 95%CI 5.39, 15.91) and control (β 8.07; 95%CI 1.62, 14.52; Cohen’s d 0.92). The increase was also seen in total PEDI scores (vs baseline 8.53; 95%CI 4.98, 12.08; vs control: β 6.87; 95%CI 1.52, 12.21; Cohen’s d 0.70). The mean change in MAS scores after 12 months of cell injection reduced compared to baseline (−1.0; 95%CI −1.31, −0.69) and control (β −0.72; 95%CI −1.18, −0.26; Cohen’s d 0.76). Regarding CP-QoL, mean changes in domains including friends and family, participation in activities, and communication were higher than the control group with a large effect size. The DTI analysis in the experimental group showed that mean FA increased (CST 0.032; 95%CI 0.02, 0.03. PTR 0.024; 95%CI 0.020, 0.028) and MD decreased (CST −0.035 × 10-3; 95%CI −0.04 × 10-3, −0.02 × 10-3. PTR −0.045 × 10-3; 95%CI −0.05 × 10-3, −0.03 × 10-3); compared to baseline. The mean changes were significantly higher than the control group. Conclusions The UCT-MSC transplantation was safe and may improve the clinical and imaging outcomes. Trial registration The study was registered with ClinicalTrials.gov (NCT03795974).

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