FACHRIZAL ARFANI PRAWIRAGARA, - (2022) AKSELERASI APOPTOSIS MELALUI JALUR EKSTRINSIK DENGAN SENSITIVASI SEKROTOM DAN CSF-2 PADA PERIPHERAL BLOOD MONONUCLEARS (PBMCS) TERHADAP MESENCHYMAL STEM SELL OSTEOSARCOMA (OS-MSCS). Thesis thesis, UNIVERSITAS AIRLANGGA.

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Abstract

Osteosarcoma is a neoplasm that can be diagnosed based on histological examination of osteoid production associated with malignant mesenchymal cells. Osteosarcoma is generally a tumor that is aggressive and tends to metastasize early and has several types, which are conventionally divided by cell type (osteoblastic, chondroblastic and fibroblastic). Osteosarcoma is the most common primary bone sarcoma. In recent years, antibody and cell-based immunotherapy approaches have been quite successful in the treatment of childhood malignancy. One of the highlights is the potential possessed by peripheral blood mononuclear cells or known internationally as Peripheral Blood Mononuclear Cells (PBMCs). PBMCs are superior to other cell-based therapeutic sources. The aim of this study is to describe the apoptosis triggered by secretome-sensitized PBMCs and GM-CSF in coculture with osteosarcoma stem cells via cytokine pathways. Physiologically PBMCs have the properties or function as clock mechanisms that regulate transcription and translation factors in tissues and immune cells that produce various kinds of pro and anti-inflammatory molecules, ligands and other cytokines from immune cells. PBMCs consist of several cells (lymphocytes (Th1, Th2, Th17), monocytes, Natural Killer Cells, dendritic cells, macrophages that have different phenotypes and activations in the immune system. In this study, the process of sensitizing PBMCs before co-cultivation with OS-MSCs is expected to increase the potency of PBMCs with these various components. In this study, secretome and GM-CSF are used as stimulators of PBMCs components. Evaluation of the stimulating effect of PBMCs in this study includes the use of crud from secretom mesenchymal stem cells (MSCs) and CSF-2 which are pure macrophage products. Both sources of active molecules have the effect of activating macrophages while the secretomes have complete components that can function as signaling molecules that can protect and enhance cells. However, when compared with the function of CSF-2 which has been shown to increase immune cell activity through the secretion of TNF-alpha and granzyme from both NK and CTL cells, it has not been shown to be more significant when compared to secretomes which cannot be explained clearly. Therefore, exploration with the HPLC approach is needed to obtain large molecular weight and small molecular weight groups such as exosomes or extravesicles and active metabolite molecules, so that in vitro concentrations are needed.

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