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Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.

ABSTRACT: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that leads to severe neurological deficits. Due to their immunomodulatory and neuroprotective activities and their ability to promote the generation of oligodendrocytes, mesenchymal stem cells (MSCs) are currently being developed for autologous cell therapy in MS. As aging reduces the regenerative capacity of all tissues, it is of relevance to investigate whether MSCs retain their pro-oligodendrogenic activity with increasing age. We demonstrate that MSCs derived from aged rats have a reduced capacity to induce oligodendrocyte differentiation of adult CNS stem/progenitor cells. Aging also abolished the ability of MSCs to enhance the generation of myelin-like sheaths in demyelinated cerebellar slice cultures. Finally, in a rat model for CNS demyelination, aging suppressed the capability of systemically transplanted MSCs to boost oligodendrocyte progenitor cell (OPC) differentiation during remyelination. Thus, aging restricts the ability of MSCs to support the generation of oligodendrocytes and consequently inhibits their capacity to enhance the generation of myelin-like sheaths. These findings may impact on the design of therapies using autologous MSCs in older MS patients.

SUBMITTER: Rivera FJ

PROVIDER: S-EPMC6618006 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.

Rivera Francisco J FJ de la Fuente Alerie G AG Zhao Chao C Silva Maria E ME Gonzalez Ginez A GA Wodnar Roman R Feichtner Martina M Lange Simona S Errea Oihana O Priglinger Eleni E O'Sullivan Anna A Romanelli Pasquale P Jadasz Janusz J JJ Brachtl Gabriele G Greil Richard R Tempfer Herbert H Traweger Andreas A Bátiz Luis F LF Küry Patrick P Couillard-Despres Sebastien S Franklin Robin J M RJM Aigner Ludwig L

Glia 20190430 8

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that leads to severe neurological deficits. Due to their immunomodulatory and neuroprotective activities and their ability to promote the generation of oligodendrocytes, mesenchymal stem cells (MSCs) are currently being developed for autologous cell therapy in MS. As aging reduces the regenerative capacity of all tissues, it is of relevance to investigate whether MSCs retain their pro-oligodendrogenic activity ...[more]

PMID: 31038798

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Project description:BackgroundBone marrow-derived mesenchymal stem cells (BM-MSCs) have been identified to be closely associated with cancer progression. Our previous experimental results showed that BM-MSCs promote tumor growth and metastasis of gastric cancer through paracrine-soluble cytokines or exosomes. However, the elements that affect the role of BM-MSCs in promoting tumor metastasis are not clear. It is known that thrombocytosis in cancer patients is very common. Recently, platelets are recognized to play a critical role in tumor progression.PurposeThis study aims to observe the effect of BM-MSCs which were co-cultured with platelets on tumor cell metastasis.MethodsPlatelet aggregation rate and the expression of P-selectin of platelets co-incubated with conditioned medium of SGC-7901 cells and BM-MSCs were detected by flow cytometry and platelet aggregometer. We also analyzed the change of BM-MSCs after co-incubation with platelets or platelets which were treated with SGC-7901 cells using transwell assay and Western blot analysis. The proliferation and migration ability and expression of VEGF, c-Myc, and sall-4 in SGC-7901 cells treated with medium of BM-MSCs which were co-cultured with platelets were detected. SGC-7901 cells were injected into Balb/c nude mice and the extent of lung metastasis was observed. Both in vitro and in vivo assays were used to analyze the effect of platelets on enhancing the ability of BM-MSCs to promote cancer metastasis.ResultsResults suggested that BM-MSCs and tumor cells can promote platelet aggregation rate and the expression of P-selectin. The protein levels of α-smooth muscle actin, vimentin, and fibroblast activation protein in BM-MSCs were higher after co-incubation with platelets, and SB431542 was used to confirm the effect of TGF-β on transdifferentiation of BM-MSCs into cancer-associated fibroblasts. Medium of BM-MSCs treated with platelets enhanced the proliferation and migration ability of SGC-7901 cells. More lung metastases were found in mice which were injected with SGC-7901 cells treated with conditioned medium from BM-MSCs co-incubated with platelets.ConclusionTumor cells and BM-MSCs activate platelets which can change the characteristics of BM-MSCs through secretion of TGF-β. Moreover, we found that platelets enhanced the effect of BM-MSCs on tumor metastasis, which suggested a potential target and approach for gastric cancer therapy.

Dataset Information

Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.

Publications

Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.

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