The impact of Mesenchymal Stem Cells and their secretome as a treatment for gliomas

Gomes, Eduardo D.; Castro, Joana Vieira de; Costa, Bruno M.; Salgado, António J.

doi:10.1016/j.biochi.2018.07.008

Cited by 22 publications

(22 citation statements)

References 87 publications

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“…Moreover, the major obstacle in the clinical application of stem cells is the possibility of malignant transformation 2728293031. Meanwhile, accumulating evidence has indicated that secretome released from stem cells exhibits similar potential as stem cells because the principal action of stem cells is mediated by the secretome 3233343536373839. Our previous experiments using secretome also demonstrated that secretome has similar, at least not inferior, therapeutic potential as stem cells in ameliorating hepatic failure 171819202140…”

Section: Discussionmentioning

confidence: 91%

Isolation of Secretome with Enhanced Antifibrotic Properties from miR-214-Transfected Adipose-Derived Stem Cells

Park

Kim

et al. 2019

J Korean Med Sci

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BackgroundSecretome refers to the total set of molecules secreted or surface-shed by stem cells. The limitations of stem cell research have led numerous investigators to turn their attention to the use of secretome instead of stem cells. In this study, we intended to reinforce antifibrotic properties of the secretome released from adipose-derived stem cells (ASCs) transfected with miR-214.MethodsWe generated miR-214-transfected ASCs, and extracted the secretome (miR214-secretome) from conditioned media of the transfected ASCs through a series of ultrafiltrations. Subsequently, we intravenously injected the miR-214-secretome into mice with liver fibrosis, and determined the effects of miR-214-secretome on liver fibrosis.ResultsCompared with that by naïve secretome, liver fibrosis was ameliorated by intravenous infusion of miR-214-secretome into mice with liver fibrosis, which was demonstrated by significantly lower expression of fibrosis-related markers (alpha-smooth muscle actin, transforming growth factor-β, and metalloproteinases-2) in the livers as well as lower fibrotic scores in the special stained livers compared with naïve secretome. The infusion of miR-214-secretome also led to lesser local and systemic inflammation, higher expression of an antioxidant enzyme (superoxide dismutase), and higher liver proliferative and synthetic function.ConclusionMicroRNA-214 transfection stimulates ASCs to release the secretome with higher antifibrotic and anti-inflammatory properties. miR-214-secretome is thus expected to be one of the prominent ways of overcoming liver fibrosis, if further studies consistently validate its safety and efficiency.

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Section: Discussionmentioning

confidence: 91%

Isolation of Secretome with Enhanced Antifibrotic Properties from miR-214-Transfected Adipose-Derived Stem Cells

Park

Kim

et al. 2019

J Korean Med Sci

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“…Walker et al 40 showed that vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype, facilitating fibrosis in wound repair, while vimentin deficiency resulted in a blunted inflammatory response. Vimentin is also a key regulator of the NLRP3 inflammasome, promoting lung inflammation and fibrosis 13 . In addition, PTX3 inhibits inflammation and leukocyte adhesion and transmigration 41 .…”

Section: Discussionmentioning

confidence: 99%

“…To overcome safety concerns, several researchers have turned to their attention to the secretome, which are the molecules that are secreted or surface-shed by stem cells 8,9 . Numerous studies have demonstrated that the secretome has similar potential to that of stem cells because the principal mechanism of action of these cells is mediated by the secretome [10][11][12][13][14][15][16][17] . We have also performed several experiments that validated the therapeutic potential of the secretome, especially for the treatment of liver diseases, and have concluded that the secretome and stem cells have similar therapeutic potential, at least for improving hepatic failure [18][19][20][21][22][23] .…”

Section: Introductionmentioning

confidence: 99%

A novel antifibrotic strategy utilizing conditioned media obtained from miR-150-transfected adipose-derived stem cells: validation of an animal model of liver fibrosis

et al. 2020

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The limitations of stem cells have led researchers to investigate the secretome, which is the secretory materials in stem cells, since the principal mechanism of action of stem cells is mediated by the secretome. In this study, we determined the antifibrotic potential of the secretome released from miR-150-transfected adipose-derived stromal cells (ASCs). The secretome released from ASCs that were transfected with antifibrotic miR-150 was obtained (referred to as the miR-150 secretome). To validate the antifibrotic effects of the miR-150 secretome, we generated in vitro and in vivo models of liver fibrosis by treating human hepatic stellate cells (LX2 cells) with thioacetamide (TAA) and subcutaneous injection of TAA into mice, respectively. In the in vitro model, more significant reductions in the expression of fibrosisrelated markers, such as TGFβ, Col1A1, and α-SMA, were observed by using the miR-150 secretome than the control secretome, specifically in TAA-treated LX2 cells. In the in vivo model, infusion of the miR-150 secretome into mice with liver fibrosis abrogated the increase in serum levels of systemic inflammatory cytokines, such as IL-6 and TNF-α, and induced increased expression of antifibrotic, proliferation, and antioxidant activity markers in the liver. Our in vitro and in vivo experiments indicate that the miR-150 secretome is superior to the naive secretome in terms of ameliorating liver fibrosis, minimizing systemic inflammatory responses, and promoting antioxidant enzyme expression. Therefore, we conclude that miR-150 transfection into ASCs has the potential to induce the release of secretory materials with enhanced antifibrotic, proliferative, and antioxidant properties.

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“…bone marrow, adipose tissue, umbilical cord blood and tumour tissue, and the phenotype of glioma cells, used for studies. The timing and mode of MSC administration to animal models may affect the interactions between MSCs and glioma in vitro deepening on the mode of interactions [26,73,79]. Further investigations are needed to deepen our understanding of the mechanisms of MSC behaviour in tumour microenvironment and their effects on glioma pathobiology before to successful MSC-based anti-cancer therapy will be developed.…”

Section: Heterotypic Interaction Cell Interactions In Animal Modelsmentioning

confidence: 99%

Kinins in Glioblastoma Microenvironment

Oliveira

Breznik

Pillat

et al. 2019

Cancer Microenvironment

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Tumour progression involves interactions among various cancer cell clones, including the cancer stem cell subpopulation and exogenous cellular components, termed cancer stromal cells. The latter include a plethora of tumour infiltrating immunocompetent cells, among which are also immuno-modulatory mesenchymal stem cells, which by vigorous migration to growing tumours and susequent transdifferentiation into various types of tumour-residing stromal cells, may either inhibit or support tumour progression. In the light of the scarce therapeutic options existing for the most malignant brain tumour glioblastoma, mesenchymal stem cells may represent a promising novel tool for cell therapy, e.g. drug delivery vectors. Here, we review the increasing number of reports on mutual interactions between mesenchymal stem cells and glioblastoma cells in their microenvironment. We particularly point out two novel aspects: the different responses of cancer cells to their microenvironmental cues, and to the signalling by kinin receptors that complement the immuno-modulating cytokine-signalling networks. Inflammatory glioblastoma microenvironment is characterised by increasing expression of kinin receptors during progressive glioma malignancy, thus making kinin signalling and kinins themselves rather important in this context. In general, their role in tumour microenvironment has not been explored so far. In addition, kinins also regulate blood brain barrier-related drug transfer as well as brain tumour angiogenesis. These studies support the ongoing research on kinin antagonists as candidates in the development of anti-invasive agents for adjuvant glioblastoma therapy. Keywords Co-culture. Glioma. Kinin receptors. Mesenchymal stem cells. Microenvironment. Tumour heterogeneity Brain Tumours-Glioblastoma Brain tumours originate from various types of cells, of which astroglial tumours being the most frequent. The World Health Organisation (WHO) distinguishes four grades of glioma, of which glioblastoma (GBM) is the most aggressive, invasive, and lethal among all types of brain tumours. Unfortunately, it is also the most common among glial tumours with 5-7 cases per 100.000 individuals yearly, and represents 50% of all gliomas [1, 2]. It is characterised by histological features such as necrosis, vascular proliferation and pleomorphism. Contrary to most tumour types, irradiation and chemotherapy has proven to be ineffective to impair long term GBM progression, demonstrating its remarkable therapeutic resistance [3-5]. Radiotherapy is combined with chemotherapy, for which the alkylating agent temozolomide has been used in most cases. There is a constant search for novel adjuvant therapeutics, including kinase inhibitors, anti-angiogenic agents and recently also immunotherapy to increase average survival of GBM patients. Several reasons for GBM resistance to therapy has been recognised, such as diffuse infiltration of cancer cells into neighbouring brain parenchyma that are hard to target by surgery [6-8]. Furthermore, the presence of het...

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The impact of Mesenchymal Stem Cells and their secretome as a treatment for gliomas

Cited by 22 publications

References 87 publications

Isolation of Secretome with Enhanced Antifibrotic Properties from miR-214-Transfected Adipose-Derived Stem Cells

Isolation of Secretome with Enhanced Antifibrotic Properties from miR-214-Transfected Adipose-Derived Stem Cells

A novel antifibrotic strategy utilizing conditioned media obtained from miR-150-transfected adipose-derived stem cells: validation of an animal model of liver fibrosis

Kinins in Glioblastoma Microenvironment

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