Mesenchymal stem cells in the osteosarcoma microenvironment: their biological properties, influence on tumor growth, and therapeutic implications

Zheng, Ying; Wang, Gangyang; Chen, Ruiling; Hua, Yingqi; Cai, Zhengdong

doi:10.1186/s13287-018-0780-x

Cited by 98 publications

(76 citation statements)

References 57 publications

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“…The action of INF-γ, TNF-α and IL-1α strengthen the growth-promoting effects of MSCs, while INF-γ, TNF-α and TGF-β enhance the ability of MSCs to promote tumor metastases. In addition, MSCs may differentiate into associated fibroblasts to cancer under the stimulation of TGF-β (9).…”

Section: Introductionmentioning

confidence: 99%

Biology and pathogenesis of human osteosarcoma (Review)

Azevedo¹,

Fernandes

et al. 2019

Oncol Lett

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Osteosarcoma (OS) is a bone tumor of mesenchymal origin, most frequently occurring during the rapid growth phase of long bones, and usually located in the epiphyseal growth plates of the femur or the tibia. Its most common feature is genome disorganization, aneuploidy with chromosomal alterations, deregulation of tumor suppressor genes and of the cell cycle, and an absence of DNA repair. This suggests the involvement of surveillance failures, DNA repair or apoptosis control during osteogenesis, allowing the survival of cells which have undergone alterations during differentiation. Epigenetic events, including DNA methylation, histone modifications, nucleosome remodeling and expression of non-coding RNAs have been identified as possible risk factors for the tumor. It has been reported that p53 target genes or those genes that have their activity modulated by p53, in addition to other tumor suppressor genes, are silenced in OS-derived cell lines by hypermethylation of their promoters. In osteogenesis, osteoblasts are formed from pluripotent mesenchymal cells, with potential for self-renewal, proliferation and differentiation into various cell types. This involves complex signaling pathways and multiple factors. Any disturbance in this process can cause deregulation of the differentiation and proliferation of these cells, leading to the malignant phenotype. Therefore, the origin of OS seems to be multifactorial, involving the deregulation of differentiation of mesenchymal cells and tumor suppressor genes, activation of oncogenes, epigenetic events and the production of cytokines. Contents 1. Introduction 2. Biology of human OS 3. Role of differentiation of mesenchymal stem cells 4. Role of DNA changes 5. Role of deregulating the expression of tumor suppressor genes 6. Regulation of oncogene expression 7. Role of epigenetic mechanisms 8. Role of non-coding RNAs 9. Role of cytokines 10. Conclusion

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Section: Introductionmentioning

confidence: 99%

Biology and pathogenesis of human osteosarcoma (Review)

Azevedo¹,

Fernandes

et al. 2019

Oncol Lett

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“…MSCs are especially known for their secretion of paracrine factors, which have beneficial effects on angiogenesis, cell survival, and restraining inflammation. 25,41,44,45 The encouraging results of opal substrate-based MSC transplantation on AMI mice in this study, as identified by decreased apoptosis of cardiomyocytes and a significant decrease of LV remodeling, are mainly due to this novel method. The secretion effects of MSCs were extremely encouraging, as shown by increased levels of SDF-1, Ang-1, and VEGF-α.…”

Section: Discussionmentioning

confidence: 72%

Inverse opal substrate-loaded mesenchymal stem cells contribute to decreased myocardial remodeling after transplantation into acute myocardial infarction mice

Dai

et al. 2018

IJN

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BackgroundThe two-dimensional incubation method is now the most commonly method for mesenchymal stem cell (MSC) production. however, gene expression and secretion of growth factors are relatively low; thus, the transplanted cells cannot be effectively utilized for potential clinical applications after acute myocardial infarction (AMI).ObjectivesWe aimed to investigate whether our newly made substrates of inverse opal with specific surface microstructures for MSC culturing can increase the viability of the cells and can contributes to decreased myocardial remodeling after transplanted to AMI mice.MethodsThe inverse opal structure is fabricated by the convenient bottom-up approach of the self-assembly of colloidal nanoparticles. Mouse-derived MSCs were then cultured on the substrates when expanded at different times to investigate the cell growth status including morphology. Then the inverse opal substrates loaded MSCs were transplanted to AMI mice, cardiomyocyte apoptosis and LV remodeling were further compared. To explore the possible mechanisms of curation, the secretions and viability of MSCs on substrates were determined using mice ELISA kits and JC-1 mitochondrial membrane potential assay kits respectively at normal and hypoxic conditions.Results6 times expanded inverse opals allowed greatly the orderly growth of MSCs as compared to four (34% ± 10.6%) and two (20%±7.2%) times expanded as well as unexpanded (13%±4.1%) (P<0.001). Nearly 90% of MSCs showed orientation angle intervals of less than 30° when at the 6X expanded (89.6%±25%) compared to the percent of cells with 30°–60° (8.7%±2.6%) or ≥60° (1.7%±1.0%) orientation angle (P<0.001). After inverse opal loaded MSCs transplanted to AMI mice, greatly decreased apoptosis of cardiomyocytes (20.45%±8.64% vs.39.63%±11.71%, P<0.001) and infarction area (5.87±2.18 mm2 vs 9.31±3.11 mm2, P<0.001) were identified. In the end, the viability of inverse opal loaded MSCs determined by membrane potential (P<0.001) and the secretion of growth factors including VEGF-α, SDF-1 and Ang-1 (P<0.001) were both confirmed significantly higher than that of the conventional culture in petri dish.ConclusionThe structure of inverse opal can not only adjust the arrangement of MSCs but also contribute to its orientated growth. Inverse opal loaded MSCs transplantation extremely curbed myocardial remodeling, the underlying mechanisms might be the high viability and extremely higher secretions of growth factors of MSCs as devoted by this method.

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“…Consequently, MSCs have autocrine and paracrine trophic properties, as their secreted growth factors stimulate cell division and differentiation of MSCs, osteoblasts, and endothelial cells [62]. Furthermore, MSCs also secrete chemokines (C-C motif) ligand 5 (CCL5), stromal derived factor 1 SDF-1 or (C-X-C motif) chemokine 12 CXCL12, interleukin 6 (IL-6), and growth factor vascular endothelial growth factor (VEGF), known, among others, to promote OS growth, metastasis spread, and angiogenesis (reviewed in Reference [63]).…”

Section: Mscs As Sensors and Modulators Of Os Microenvironmentmentioning

confidence: 99%

The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem

Corre

Verrecchia

Crenn

et al. 2020

Cells

308

271

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Osteosarcomas are the most frequent primary bone sarcomas, affecting mainly children, adolescents, and young adults, and with a second peak of incidence in elderly individuals. The current therapeutic management, a combined regimen of poly-chemotherapy and surgery, still remains largely insufficient, as patient survival has not improved in recent decades. Osteosarcomas are very heterogeneous tumors, both at the intra- and inter-tumor level, with no identified driver mutation. Consequently, efforts to improve treatments using targeted therapies have faced this lack of specific osteosarcoma targets. Nevertheless, these tumors are inextricably linked to their local microenvironment, composed of bone, stromal, vascular and immune cells and the osteosarcoma microenvironment is now considered to be essential and supportive for growth and dissemination. This review describes the different actors of the osteosarcoma microenvironment and gives an overview of the past, current, and future strategies of therapy targeting this complex ecosystem, with a focus on the role of extracellular vesicles and on the emergence of multi-kinase inhibitors.

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Mesenchymal stem cells in the osteosarcoma microenvironment: their biological properties, influence on tumor growth, and therapeutic implications

Cited by 98 publications

References 57 publications

Biology and pathogenesis of human osteosarcoma (Review)

Biology and pathogenesis of human osteosarcoma (Review)

Inverse opal substrate-loaded mesenchymal stem cells contribute to decreased myocardial remodeling after transplantation into acute myocardial infarction mice

The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem

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