Innovating Glioma Therapy Using Secretions from Umbilical Cord Mesenchymal Stem Cells to Target Homeobox and Growth Factor Genes

Ahmad Faried; Achmad Adam; Wahyu Widowati; Annisa Firdaus Sutendi; Faradhina Salfa Nindya; William Junino Saputro; Dhanar Septyawan Hadiprasetyo

doi:10.18502/ijhoscr.v19i1.17820

Ahmad Faried Department of Neurosurgery, Faculty of Medicine, Padjadjaran University, Bandung 40161, West Java, Indonesia
Achmad Adam Department of Neurosurgery, Faculty of Medicine, Padjadjaran University, Bandung 40161, West Java, Indonesia
Wahyu Widowati Faculty of Medicine, Maranatha Christian University, Bandung 40164, Indonesia
Annisa Firdaus Sutendi Biomolecular and Biomedicine Research Center, Aretha Medika Utama, Bandung 40163, Indonesia
Faradhina Salfa Nindya Biomolecular and Biomedicine Research Center, Aretha Medika Utama, Bandung 40163, Indonesia
William Junino Saputro Biology Study Program, Faculty of Mathematics and Natural Sciences Education, Universitas Pendidikan Indonesia. Bandung 40154, Indonesia
Dhanar Septyawan Hadiprasetyo Faculty of Pharmacy, Universitas Jenderal Achmad Yani, Cimahi 40531, West Java, Indonesia

DOI: https://doi.org/10.18502/ijhoscr.v19i1.17820

Keywords: Cytotoxic; mRNA expression; Glioblastoma therapy; human umbilical cord mesenchymal stem cells (hUCMSCs); Secretome

Abstract

Background: Glioblastoma is a prevalent and challenging malignant brain tumor. Secretome therapy using human umbilical cord mesenchymal stem cells (hUCMSCs) appears to be a promising treatment for glioblastoma. This study analyzed the potential of the hUCMSC secretomes (hUCMSCs-sec) for glioma therapy.

Materials and Methods: Characterization of hUCMSCs was performed by examining certain markers, including CD44, CD90, CD105, CD73, CD13, CD19, CD14, CD45, CD34, and HLA-D. The cells’ ability to differentiate into adipocytes, chondrocytes, and osteocytes was evaluated. Cytotoxic effect on Glioblastoma (GBM) cells was analyzed using 2-[2-methoxy-4-nitrophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H-tetrazolium (WST-8). mRNA relative expression, including homeobox (HOXA5, HOXB1, HOXC9 and HOXC10), insulin-like growth factor binding protein 2 (IGFBP2), Extracellular signal-regulated kinases (ERK), Epidermal growth factor receptor (EGFR), and Caspase 3 (Casp3), were quantified by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR).

Results: The hUCMSCs-sec was successfully isolated and identified, showing positive markers and its capacity to differentiate into chondrocytes, adipocytes, and osteocytes. hUCMSCs-sec exerted a cytotoxic effect on GBM cells and upregulated the expression of Casp3, whereas it decreased the expression of HOX, IGFBP2, EGFR, and ERK in GBM cells.

Conclusion: The secretomes from hUCMSCs show potential for GBM cell therapy by improving the deregulation of HOX, inducing apoptosis, and inhibiting cell proliferation genes.