1.Advancing towards Effective Glioma Therapy: MicroRNA Derived from Umbilical Cord Mesenchymal Stem Cells’ Extracellular Vesicles
Eko Ngadiono ; Novi Silvia Hardiany
Malaysian Journal of Medical Sciences 2019;26(4):5-16
A glioma, especially a grade IV glioblastoma, is a malignant tumour with a poor prognosis
despite growing medical advancements. Researchers have been looking for better and more
effective treatments targeting the molecular pathways of gliomas due to glioblastomas’ ability
to develop resistance to chemotherapies. Moreover, glioma stem cells (GSC) contribute to
maintaining the glioma population, which benefits from its ability to self-renew and differentiate.
Recent research has reported that through the introduction of umbilical cord mesenchymal
stem cells (UCMSC) into glioma cells, the growth and development of the glioma cells can be
downregulated. It has more currently been found out that UCMSC release extracellular vesicles
(EVs) containing miRNA that are responsible for this phenomenon. Therefore, this review analyses
literature to discuss all possible miRNAs contained within the UCMSC’s EVs and to elaborate on
their molecular mechanisms in halting gliomas and GSC growth. This review will also include the
challenges and limitations, to account for which more in vivo research is suggested. In conclusion,
this review highlights how miRNAs contained within UCMSC’s EVs are able to downregulate
multiple prominent pathways in the survival of gliomas.
2.Gene Expression of Molecules Regulating Apoptotic Pathways in Glioblastoma Multiforme Treated with Umbilical Cord Stem Cell Conditioned Medium
Novi Silvia Hardiany ; Edward Christopher Yo ; Eko Ngadiono ; Septelia Inawati Wanandi
Malaysian Journal of Medical Sciences 2019;26(6):35-45
Background: Glioblastoma multiforme (GBM) is the most malignant primary brain
tumour and there is no definite cure. It has been suggested that there are significant interactions
among mesenchymal stem cells (MSCs), their released factors and tumour cells that ultimately
determine GBM’s growth pattern. This study aims to analyse the expression of molecules involved
in GBM cell apoptotic pathways following treatment with the MSC secretome.
Methods: A conditioned medium of umbilical cord-derived MSCs (UCMSC-CM) was
generated by culturing the cells on serum-free αMEM for 24 h. Following this, human GBM T98G
cells were treated with UCMSC-CM for 24 h. Quantitative reverse transcriptase-polymerase chain
reaction (qRT-PCR) was then performed to measure the mRNA expression of survivin, caspase-9,
TNF-related apoptosis-inducing ligand (TRAIL), DR4 and DcR1.
Results: mRNA expression of caspase-9 in CM-treated T98G cells increased 1.6-fold
(P = 0.017), whereas mRNA expression of survivin increased 3.5-fold (P = 0.002). On the other
hand, TRAIL protein expression was upregulated (1.2-fold), whereas mRNA expression was
downregulated (0.4-fold), in CM-treated cells. Moreover, there was an increase in the mRNA
expression of both DR4 (3.5-fold) and DcR1 (1,368.5-fold) in CM-treated cells.
Conclusion: The UCMSC-CM was able to regulate the expression of molecules involved
in GBM cell apoptotic pathways. However, the expression of anti-apoptotic molecules was more
upregulated than that of pro-apoptotic molecules.