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Role of Mesenchymal Stem Cells in Progression of Multiple Myeloma

By: Kayci Reyer
Posted: Wednesday, April 3, 2019

Research published in Scientific Reports found that mesenchymal stem cells from patients with multiple myeloma (MM-MSC) have a unique gene-expression profile compared with mesenchymal stem cells from normal donors (ND-MSC). Researchers sought to determine how tumor microenvironment, particularly for bone marrow mesenchymal stem cells, may affect the progression and management of multiple myeloma.

“Our results suggest that MM-MSC have constitutive abnormalities that remain present even in the absence of tumors cells,” concluded Rodrigo Carlini Fernando, PhD, of the Federal University of São Paulo, Brazil, and colleagues. “The alterations found in cell-cycle progression, immune system activation, and osteoblastogenesis suggest, respectively, that MM-MSC are permanently dependent [on] tumor cells, might contribute to immune evasion and play an essential role in bone lesions frequently found in [multiple myeloma] patients.”

Compared with ND-MSC, MM-MSC were found to have 485 differentially expressed genes, with 280 upregulated and 205 downregulated. To determine this unique expression, researchers used gene-expression analysis of both MM-MSC and ND-MSC after an in vitro expansion. The investigators then selected certain genes to undergo functional in vitro analysis as well as quantitative real-time polymerase chain reaction analysis.

These analyses showed that the primary function of downregulated differentially expressed genes was associated with cell-cycle progression, immune response activation, and bone metabolism. Specifically, researchers found that quantitative real-time polymerase chain reaction validated two genes related to bone metabolism—ZNF521 and SEMA3A—as well as two involved in immune response activation—HLA-DRA and CHIRL1.

“Due to the essential role of these cells in the maintenance and progression of MM, potential therapeutic targets and new drugs capable of disrupting the interactions between MM-MSC and MM cells are welcome,” the investigators concluded.

Disclosure: The study authors reported no conflicts of interest.



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