1. Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice
- Author
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Eustathios Kenanidis, Kenneth Dalgarno, Eleftherios Tsiridis, Theodosios Stamatopoulos, Kenneth S. Rankin, Ricardo Ribeiro, Alexandros Stamatopoulos, Zakareya Gamie, and Craig Gerrand
- Subjects
lcsh:Diseases of the musculoskeletal system ,MMP2/9, matrix metalloproteinase-2/9 ,SCF, stem cells factor ,medicine.medical_treatment ,Review Article ,CCL5, chemokine ligand 5 ,TNF, tumour necrosis factor ,Regenerative medicine ,APCs, antigen presenting cells ,0302 clinical medicine ,Stromal ,Medicine ,HER2, human epidermal growth factor receptor 2 ,TNF-a, tumour necrosis factor alpha ,IL-6, interleukin-6 ,Sarcoma ,MCP-1, monocyte chemoattractant protein-1 ,TGF-b1, transforming growth factor beta 1 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,ECM, extracellular matrix ,hMSCs, human mesenchymal stromal cells ,IFN-β, interferon beta ,VEGFR, vascular endothelial growth factor receptor ,Oncology ,030220 oncology & carcinogenesis ,MMP-2, matrix metalloproteinase-2 ,CXCL12/CXCR7, C-X-C chemokine ligand 12/ C-X-C chemokine receptor 7 ,GD2, disialoganglioside 2 ,IL11RA, Interleukin 11 Receptor Subunit Alpha ,CXCR4, chemokine receptor type 4 ,lcsh:RC254-282 ,CCR2, chemokine receptor 2 ,03 medical and health sciences ,IL-1b, interleukin-1b ,PGE2, prostaglandin E2 ,TAAs, tumour-associated antigens ,Regeneration ,ASC, adipose-derived stromal/stem cells ,Bone regeneration ,Biology ,Tissue ,CD, classification determinants ,IFN-γ, interferon gamma ,DKK1, dickkopf-related protein 1 ,Mesenchymal stem cell ,Orthopaedic ,medicine.disease ,Radiation therapy ,030104 developmental biology ,IGF-1R, insulin-like growth factor 1 receptor ,OPG, osteoprotegerin ,Cancer cell ,FGF-2, fibroblast growth factors-2 ,Cell ,CLUAP1, clusterin associated protein 1 ,RES, reticuloendothelial system ,CAM, cell adhesion molecules ,CSPG4, Chondroitin sulfate proteoglycan 4 ,IL-2a, interleukin-2a ,0301 basic medicine ,MAGE, melanoma antigen gene ,PDGF, platelet-derived growth factor ,HMGB1/RACE, high mobility group box-1 protein/ receptor for advanced glycation end-products ,PI3K/Akt, phosphoinositide 3-kinase/protein kinase B ,BD, bone defect ,TRAIL, tumour necrosis factor related apoptosis-inducing ligand ,BMMSCs, bone marrow-derived mesenchymal stromal cells ,IL-8, interleukin-8 ,PEDF, pigment epithelium-derived factor ,TCR, T cell receptor ,IL-21, interleukin-21 ,NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells ,IL-18, interleukin-18 ,IL-10, interleukin-10 ,VEGF, vascular endothelial growth factor ,IDO, indoleamine 2,3-dioxygenase ,EMT, epithelial-mesenchymal transition ,CX3CL1, chemokine (C-X3-C motif) ligand 1 ,MRP, multidrug resistance protein ,TGF-b, transforming growth factor beta ,Mesenchymal ,Stromal cell ,CXCL12/CXCR4, C-X-C chemokine ligand 12/ C-X-C chemokine receptor 4 ,PBS, phosphate-buffered saline ,RANK, receptor activator of nuclear factor kappa-B ,Bone Sarcoma ,IFN-α, interferon alpha ,STAT-3, signal transducer and activator of transcription 3 ,PDX, patient derived xenograft ,RANKL, receptor activator of nuclear factor kappa-B ligand ,SDF-1, stromal cell-derived factor 1 ,IL-12, interleukin-12 ,MSCs, mesenchymal stem/stromal cells ,5-FC, 5-fluorocytosine ,Bone ,WBCs, white blood cell ,business.industry ,AAT, a1-antitrypsin ,PTX, paclitaxel ,Ang1, angiopoietin-1 ,rh-TRAIL, recombinant human tumour necrosis factor related apoptosis-inducing ligand ,CD, cytosine deaminase ,RBCs, red blood cells ,RNA, ribonucleic acid ,Cancer research ,FGF-7, fibroblast growth factors-7 ,SC, stem cells ,HGF, hepatocyte growth factor ,DBM, Demineralized Bone Marrow ,lcsh:RC925-935 ,business ,Abs, antibodies - Abstract
Highlights • The tumour microenvironment promotes induction of mesenchymal stromal cells through the production of soluble factors. • Data from animal models indicates that mesenchymal stromal cells could accelerate pulmonary metastases, promote proliferation of sarcoma cells and increase chemoresistance. • Pre-activated and use of transduced mesenchymal stromal cells have a positive effect on bone sarcoma. • There is preliminary clinical evidence for mesenchymal stromal cell in promoting bone regeneration within large bone defects after surgical excision., Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cells selectively. Recently, Mesenchymal Stromal Cells (MSCs) have been the subject of significant research in orthopaedic clinical practice through their use in regenerative medicine. Further research has been directed at the use of MSCs for more personalized bone sarcoma treatments, taking advantage of their wide range of potential biological functions, which can be augmented by using tissue engineering approaches to promote healing of large defects. In this review, we explore the use of MSCs in bone sarcoma treatment, by analyzing MSCs and tumour cell interactions, transduction of MSCs to target sarcoma, and their clinical applications on humans concerning bone regeneration after bone sarcoma extraction.
- Published
- 2019