ABSTRACT
Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematological clonal disorders. Here, we have tested the bone marrow (BM) cells from 38 MDS patients covering all risk groups in two immunodeficient mouse models: NSG and NSG-S. Our data show comparable level of engraftment in both models. The level of engraftment was patient specific with no correlation to any specific MDS risk group. Furthermore, the co-injection of mesenchymal stromal cells (MSCs) did not improve the level of engraftment. Finally, we have developed an in vitro two-dimensional co-culture system as an alternative tool to in vivo. Using our in vitro system, we have been able to co-culture CD34+ cells from MDS patient BM on auto- and/or allogeneic MSCs over 4 weeks with a fold expansion of up to 600 times. More importantly, these expanded cells conserved their MDS clonal architecture as well as genomic integrity.
Subject(s)
Bone Marrow Cells/pathology , Myelodysplastic Syndromes/pathology , Animals , Biomarkers , Bone Marrow Transplantation , Chromosome Aberrations , Disease Models, Animal , Female , Gene Expression , Genes, Reporter , Heterografts , Humans , Immunophenotyping , Male , Mesenchymal Stem Cells , Mice , Mice, Knockout , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/metabolismABSTRACT
Porous scaffolds are widely tested materials used for various purposes in tissue engineering. A critical feature of a porous scaffold is its ability to allow cell migration and growth on its inner surface. Up to now, there has not been a method to locate live cells deep inside a material, or in an entire structure, using real-time imaging and a non-destructive technique. Herein, we seek to demonstrate the feasibility of the magnetic resonance imaging (MRI) technique as a method to detect and locate in vitro non-labelled live cells in an entire porous material. Our results show that the use of optimized MRI parameters (4.7 T; repetition time = 3000 ms; echo time = 20 ms; resolution 39 × 39 µm) makes it possible to obtain images of the scaffold structure and to locate live non-labelled cells in the entire material, with a signal intensity higher than that obtained in the culture medium. In the current study, cells are visualized and located in different kinds of porous scaffolds. Moreover, further development of this MRI method might be useful in several three-dimensional biomaterial tests such as cell distribution studies, routine qualitative testing methods and in situ monitoring of cells inside scaffolds.
Subject(s)
Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Tissue Scaffolds , Animals , Cell Line , Ceramics/chemistry , Mice , PorosityABSTRACT
Over the last decade, genetic and cell biology studies have indicated that tumour growth is not only determined by malignant cancer cells themselves, but also by the tumour microenvironment. Cells present in the tumour microenvironment include fibroblasts, vascular, smooth muscle, adipocytes, immune cells and mesenchymal stem cells (MSC). The nature of the relationship between MSC and tumour cells appears dual and whether MSC are pro- or anti-tumorigenic is a subject of controversial reports. This review is focused on the role of MSC and bone marrow (BM) niches in cancer (AU)
Subject(s)
Humans , Animals , Male , Female , Bone Marrow Cells/pathology , Neoplasms/drug therapy , Neoplasms/pathology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/pathology , Stem Cell Niche , Antineoplastic Agents/pharmacology , Bone Marrow Cells , Bone Marrow Cells/physiology , Drug Resistance, Neoplasm/physiology , Neoplasm Metastasis , Tumor Microenvironment/drug effects , Tumor Microenvironment/physiology , Mesenchymal Stem Cells/physiology , Stem Cell Niche/physiologyABSTRACT
Considering the design and development of biomaterials used in tissue engineering, not only is it important that they are biocompatible but also that they induce the desired cellular response for tissue regeneration. Chitosan, a biocompatible and bioresorbable polymer of N-acetylglucosamine and glucosamine is used in our work combined with recombinant human BMP-2 (rhBMP-2), a potentially useful activation factor for bone repair. In this way, we try to combine the biological and filmogenic properties of this biopolymer with the osseoinductive ability of the rhBMP-2. Results showed that the chitosan films employed, without and with rhBMP-2 activation, are able to support cellular growth and proliferation on them and that only the rhBMP-2 activated ones are able to differentiate from a myoblastic mouse cell line (C2C12) toward osteoblastic phenotype. Osseoinduction properties of rhBMP-2 activated films persist for a long storage time. The in vivo experiments performed confirm the expectative created by the in vitro results obtained and are an indication that rhBMP-2 activated chitosan films could be a very attractive biomaterial for the enhancement of osseointegration of surgical prostheses and implants and for the purpose of tissue engineering bone regeneration.
