Epigenetic regulation of amniotic fluid mesenchymal stem cell differentiation to the mesodermal lineages at normal and fetus‐diseased gestation

Abstract

Human mesenchymal stem cells isolated from amniotic fluid (AF‐MSCs) demonstrate the potency for self‐renewal and multidifferentiation, and can, therefore, be a potential alternative source of stem cells adapted for therapeutic purposes. The object of this study is to evaluate the efficacy of MSCs from AF when the pregnancy is normal or when the fetus is affected during pregnancy to differentiate into mesodermal lineage tissues and to elucidate epigenetic states responsible for terminal adipogenic and osteogenic differentiation. The morphology of AF‐MSCs from two cell sources and the expression of the cell surface‐specific (CD44, CD90, and CD105) markers and pluripotency (Oct4, Nanog, Sox2, and Rex1) genes were quite similar and underwent mesodermal lineage differentiation because this is shown by the typical cell morphology and of genes’ expression specific for adipogenic (peroxisome proliferator‐activated receptor‐ɣ, adiponectin) and osteoblastic (alkaline phosphatase, osteopontin, and osteocalcin) differentiation. Terminal lineage‐specific differentiation was related to differential expression of miR‐17, miR‐21, miR‐34a, and miR‐146a, decreased levels of acetylated H4 and H3K9, trimethylated H3K4 and H3K9, and the retention of H3K27me3 along with a reduction in the levels of HDAC1, DNMT1, and PRC1/2 proteins (BMI1/SUZ12). No significant distinction could be identified in the levels of expression of all epigenetic or pluripotency markers between undifferentiated MSCs isolated from AF of normal gestation and pregnancy where the fetus was damaged and between those differentiated toward adipocytes or osteoblasts. The expressional changes of those marks and microRNAs that occurred during terminal differentiation to mesodermal tissues indicate subtle epigenetic regulation in AF‐MSCs when the condition of the fetus is healthy normal or diseased. More detailed studies of epigenetic mechanisms may offer a better understanding of AF‐MSCs differentiation in fetus‐diseased conditions and their usage in an autologous therapeutic application and prenatal disease research.

Melatonin-induced suppression of DNA methylation promotes odontogenic differentiation in human dental pulp cells

“…This result was consistent with a previous report that the suppression of DNMT1 resulted in elevating the efficiency of odontoblastic differentiation of mouse dental papilla cells [ 13 ]. In human MSCs, induction of osteogenic differentiation has been found to be associate with the decline of DNMT1 [ 29 ]. Gasiuniene et al [ 30 ] reported that osteogenic differentiation of MSCs was related to the gradual decrease in the level of DNMT1.…”

Metabolic Profile and Neurogenic Potential of Human Amniotic Fluid Stem Cells From Normal vs. Fetus-Affected Gestations

“…Aforementioned differences could possibly be explained by considering the gestational age of investigated cells, as in our study, hAFSCs were obtained from 16 to 17 weeks of normal gestations, whereas hAFSCs from polyhydramnios were obtained at 32 weeks. Although some studies, also including our previous research, showed that hAFSCs may be comparably potent in their ability to differentiate to certain lineages despite their differences in gestational age (Hamid et al, 2017;Gasiūnienė et al, 2019b;Zentelytė et al, 2020), other studies contradict this notion (Shaw et al, 2017;Huang et al, 2020). Furthermore, it is argued that pluripotent SCs typically have a lower rate of OXPHOS and maintain higher mitochondrial membrane potential in comparison to more differentiated SCs (Tsogtbaatar et al, 2020).…”

“…It should also be emphasized that scientific data about hAFSCs derived from fetus-affected gestations are very limited. Our group previously showed that hAFSCs from normal and fetus-affected gestations had similar stem cell characteristics and potential to differentiate toward mesodermal (adipogenic, osteogenic, chondrogenic, and myogenic) as well as ectodermal (neurogenic) lineages (Gasiūnienė et al, 2019b;Zentelytė et al, 2020). However, no scientific data exist on the metabolic characteristics of these two types of hAFSCs, nor are there any data on the neurogenic and neurotrophic potential of hAFSCs obtained exclusively from polyhydramnios samples.…”

Applications of human amniotic fluid stem cells in wound healing

“…As medical wastes, the stable cell lines of AFSCs can be obtained via amniocentesis during the pregnancy intermediate stage or cesarean section [3] . Compared with ESCs and iPSCs, the ability of AFSCs to multi-differentiate is limited, but they do not have the risk of teratoma formation [7] . In addition to these desirable properties, AFSCs participate in immunomodulation, regulate inflammation, and are universally histocompatible [8] .…”