Human-stimulated oocyte extract induces genetic and mitochondrial reprogramming of mesenchymal stromal cells

Reprogramming autologous adult cells to pluripotent cells allows for relatively safe cell replacement therapy. This can be achieved by nuclear transfer, cell fusion, or induced pluripotent stem cell technology However, the epigenetic memory of the cell is considered as a great challenge facing the c...

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Published in:	PloS one 2020-05, Vol.15 (5), p.e0232759-e0232759
Main Authors:	El-Gammal, Zaynab, AlOkda, Abdelrahman, Ali, Sameh S, Reda, Asmaa, Magdeldin, Sameh, Mansour, Ragaa, El-Badri, Nagwa
Format:	Article
Language:	eng
Subjects:	Autografts Bioenergetics Biology and Life Sciences Biomarkers Bone marrow Cell differentiation Cell fusion Cell proliferation Composition Cristae Embryos Epigenetic inheritance Epigenetics Fertilization Fibroblasts Flow cytometry Gametocytes Gene expression Genes Genetic aspects Hematopoietic stem cells Localization Medicine and Health Sciences Membrane potential Mesenchymal stem cells Mesenchyme Metaphase Methods Microscopy Mimicry Mitochondria Morphology Nuclear fusion Nuclear reprogramming Nuclear transfer Nuclei (cytology) Oct-4 protein Oocytes Oxidative phosphorylation Oxygen Phenotypes Phosphatase Phosphorylation Pluripotency Proteins Reactive oxygen species Research and Analysis Methods Stem cells Stromal cells Technology
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Summary:	Reprogramming autologous adult cells to pluripotent cells allows for relatively safe cell replacement therapy. This can be achieved by nuclear transfer, cell fusion, or induced pluripotent stem cell technology However, the epigenetic memory of the cell is considered as a great challenge facing the complete reprograming of cells by these methods. Introducing oocyte-specific factors into differentiated cells may present a promising approach by mimicking cellular reprogramming during fertilization. Human bone marrow mesenchymal stromal cells (hBM-MSCs) were cultured with different concentrations of human metaphase II (M II) oocyte extract (0.1, 1, 5, 10, 30 ng/μl). Reprogramming was assessed at various exposure times (1, 4, 7 days). Cells were tested for their proliferation rate, morphological changes, expression of pluripotency markers, expression of mesenchymal to epithelial transition markers, and mitochondrial rejuvenation. (mitochondrial localization, morphological changes, bioenergetics, transmembrane potential, and levels of reactive oxygen species, ROS). Treatment of human BM-MSCs with 10 ng/μl oocyte extract resulted in increased cell proliferation, which was associated with the upregulation of the pluripotency genes OCT-4, NANOG, and SOX-2 and a concomitant downregulation of mesenchymal-specific genes. MSCs exhibited small, immature round mitochondria with few swollen cristae localized proximal to the cell nucleus. This was accompanied by morphological cell changes, a metabolic shift towards oxidative phosphorylation, a high mitochondrial membrane potential, and increased ROS production. These data show that treatment with 10 ng/μl human MII-phase oocyte extract induced genetic and mitochondrial reprogramming of human BM-MSCs to a more embryonic phenotype.
ISSN:	1932-6203 1932-6203