TRAIL delivered by mesenchymal stromal/stem cells counteracts tumor development in orthotopic Ewing sarcoma models

Romain Guiho; Kevin Biteau; Giulia Grisendi; Julien Taurelle; Mathias Chatelais; Malika Gantier; Dominique Heymann; Massimo Dominici; Françoise Redini

doi:10.1002/ijc.30402

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

Mediators of Inflammation ◽

10.1155/2016/7314016 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 16

Author(s):

Drenka Trivanović ◽

Jelena Krstić ◽

Ivana Okić Djordjević ◽

Slavko Mojsilović ◽

Juan Francisco Santibanez ◽

...

Keyword(s):

Stem Cells ◽

Immune Response ◽

Tumor Microenvironment ◽

Tumor Tissue ◽

Tumor Development ◽

Antitumor Therapy ◽

Delivery Vehicles ◽

Stromal Stem Cells ◽

Immunomodulatory Potential ◽

Functional Phenotype

State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.

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Recent approaches for isolating and culturing mouse bone marrow-derived mesenchymal stromal stem cells

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200708134337 ◽

2020 ◽

Vol 15 ◽

Author(s):

Basem M. Abdallah ◽

Hany M. Khattab

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Molecular Mechanisms ◽

Replicative Senescence ◽

Cellular Heterogeneity ◽

High Yield ◽

Mouse Strains ◽

Mouse Bone Marrow ◽

Differentiation Potential ◽

Stromal Stem Cells

: The isolation and culture of murine bone marrow-derived mesenchymal stromal stem cells (mBMSCs) have attracted great interest in terms of the pre-clinical applications of stem cells in tissue engineering and regenerative medicine. In addition, culturing mBMSCs is important for studying the molecular mechanisms of bone remodelling using relevant transgenic mice. Several factors have created challenges in the isolation and high-yield expansion of homogenous mBMSCs; these factors include low frequencies of bone marrow-derived mesenchymal stromal stem cells (BMSCs) in bone marrow, variation among inbred mouse strains, contamination with haematopoietic progenitor cells (HPCs), the replicative senescence phenotype and cellular heterogeneity. In this review, we provide an overview of nearly all protocols used for isolating and culturing mBMSCs with the aim of clarifying the most important guidelines for culturing highly purified mBMSC populations retaining in vitro and in vivo differentiation potential.

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Hypoxic Culture Conditions for Mesenchymal Stromal/Stem Cells from Wharton’s Jelly: A Critical Parameter to Consider in a Therapeutic Context

Current Stem Cell Research & Therapy ◽

10.2174/1574888x09666140213204850 ◽

2014 ◽

Vol 9 (4) ◽

pp. 306-318 ◽

Cited By ~ 20

Author(s):

Loic Reppel ◽

Talar Margossian ◽

Layale Yaghi ◽

Philippe Moreau ◽

Nathalie Mercier ◽

...

Keyword(s):

Stem Cells ◽

Critical Parameter ◽

Culture Conditions ◽

Wharton’S Jelly ◽

Wharton's Jelly ◽

Therapeutic Context ◽

Stromal Stem Cells

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Induction of Stem Cell Like Cells from Mouse Embryonic Fibroblast by Short-Term Shear Stress and Vitamin C

Applied Sciences ◽

10.3390/app11041941 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1941

Author(s):

Seungmin Yeom ◽

Myung Chul Lee ◽

Shambhavi Pandey ◽

Jaewoon Lim ◽

Sangbae Park ◽

...

Keyword(s):

Stem Cells ◽

Shear Stress ◽

Stem Cell ◽

Vitamin C ◽

Suspension Culture ◽

Small Molecules ◽

Tumor Development ◽

Embryonic Stem ◽

Short Term ◽

External Stimuli

Induced pluripotent stem cells (iPSCs) are a good medicine source because of their potential to differentiate into various tissues or cells. However, traditionally, iPSCs made by specific transgenes and virus vectors are not appropriate for clinical use because of safety concerns and risk of tumor development. The goal of this research was to develop an alternative method for reprogramming, using small molecules and external stimuli. Two groups were established: short-term shear stress (STSS) under suspension culture and a combination of short-term shear stress and vitamin C (SSVC) under suspension culture. For STSS, the pipetting was carried out for cells twice per day for 2 min for 14 days in the embryonic stem cell (ES) medium. In the case of SSVC, the procedure was the same as for STSS however, its ES medium included 10 µM of vitamin C. After 14 days, all spheroids were picked and checked for pluripotency by ALP (alkaline phosphatase) assay and immunocytochemistry. Both groups partially showed the characteristics of stem cells but data demonstrated that the spheroids under shear stress and vitamin C had improved stem cell-like properties. This research showed the possibility of external stimuli and small molecules to reprogram the somatic cells without the use of transgenes.

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Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02131-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Gertraud Eylert ◽

Reinhard Dolp ◽

Alexandra Parousis ◽

Richard Cheng ◽

Christopher Auger ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Low Dose ◽

Dose Range ◽

High Dose ◽

Full Thickness ◽

Burn Wound ◽

Dermal Regeneration Template ◽

Yorkshire Pigs ◽

Stromal Stem Cells

Abstract Background Multipotent mesenchymal stromal/stem cell (MSC) therapy is under investigation in promising (pre-)clinical trials for wound healing, which is crucial for survival; however, the optimal cell dosage remains unknown. The aim was to investigate the efficacy of different low-to-high MSC dosages incorporated in a biodegradable collagen-based dermal regeneration template (DRT) Integra®. Methods We conducted a porcine study (N = 8 Yorkshire pigs) and seeded between 200 and 2,000,000 cells/cm2 of umbilical cord mesenchymal stromal/stem cells on the DRT and grafted it onto full-thickness burn excised wounds. On day 28, comparisons were made between the different low-to-high cell dose groups, the acellular control, a burn wound, and healthy skin. Result We found that the low dose range between 200 and 40,000 cells/cm2 regenerates the full-thickness burn excised wounds most efficaciously, followed by the middle dose range of 200,000–400,000 cells/cm2 and a high dose of 2,000,000 cells/cm2. The low dose of 40,000 cells/cm2 accelerated reepithelialization, reduced scarring, regenerated epidermal thickness superiorly, enhanced neovascularization, reduced fibrosis, and reduced type 1 and type 2 macrophages compared to other cell dosages and the acellular control. Conclusion This regenerative cell therapy study using MSCs shows efficacy toward a low dose, which changes the paradigm that more cells lead to better wound healing outcome.

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3D Functional Corneal Stromal Tissue Equivalent Based on Corneal Stromal Stem Cells and Multi-Layered Silk Film Architecture

PLoS ONE ◽

10.1371/journal.pone.0169504 ◽

2017 ◽

Vol 12 (1) ◽

pp. e0169504 ◽

Cited By ~ 32

Author(s):

Chiara E. Ghezzi ◽

Benedetto Marelli ◽

Fiorenzo G. Omenetto ◽

James L. Funderburgh ◽

David L. Kaplan

Keyword(s):

Stem Cells ◽

Tissue Equivalent ◽

Stromal Tissue ◽

Stromal Stem Cells ◽

Silk Film

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Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

Antibiotics ◽

10.3390/antibiotics10070750 ◽

2021 ◽

Vol 10 (7) ◽

pp. 750

Author(s):

Pasquale Marrazzo ◽

Valeria Pizzuti ◽

Silvia Zia ◽

Azzurra Sargenti ◽

Daniele Gazzola ◽

...

Keyword(s):

Stem Cells ◽

Defense Mechanisms ◽

Live Cells ◽

Label Free ◽

Bacterial Diseases ◽

Prospective Application ◽

Therapy Strategies ◽

Stromal Stem Cells ◽

Different Sources

Antibiotic resistance is creating enormous attention on the development of new antibiotic-free therapy strategies for bacterial diseases. Mesenchymal stromal stem cells (MSCs) are the most promising candidates in current clinical trials and included in several cell-therapy protocols. Together with the well-known immunomodulatory and regenerative potential of the MSC secretome, these cells have shown direct and indirect anti-bacterial effects. However, the low reproducibility and standardization of MSCs from different sources are the current limitations prior to the purification of cell-free secreted antimicrobial peptides and exosomes. In order to improve MSC characterization, novel label-free functional tests, evaluating the biophysical properties of the cells, will be advantageous for their cell profiling, population sorting, and quality control. We discuss the potential of emerging microfluidic technologies providing new insights into density, shape, and size of live cells, starting from heterogeneous or 3D cultured samples. The prospective application of these technologies to studying MSC populations may contribute to developing new biopharmaceutical strategies with a view to naturally overcoming bacterial defense mechanisms.

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CD90low glioma-associated mesenchymal stromal/stem cells promote temozolomide resistance by activating FOXS1-mediated epithelial-mesenchymal transition in glioma cells

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02458-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Bing-zhou Xue ◽

Wei Xiang ◽

Qing Zhang ◽

Hao-fei Wang ◽

Yu-jie Zhou ◽

...

Keyword(s):

Stem Cells ◽

Cell Line ◽

Epithelial Mesenchymal Transition ◽

Chemotherapy Resistance ◽

Glioma Cells ◽

Conditioned Media ◽

Cell Counting ◽

Mesenchymal Transition ◽

Mesenchymal Transformation ◽

Stromal Stem Cells

Abstract Background The tumour microenvironment contributes to chemotherapy resistance in gliomas, and glioma-associated mesenchymal stromal/stem cells (gaMSCs) are important stromal cell components that play multiple roles in tumour progression. However, whether gaMSCs affect chemotherapy resistance to the first-line agent temozolomide (TMZ) remains unclear. Herein, we explored the effect and mechanism of gaMSCs on resistance to TMZ in glioma cells. Methods Human glioma cells (cell line U87MG and primary glioblastoma cell line GBM-1) were cultured in conditioned media of gaMSCs and further treated with TMZ. The proliferation, apoptosis and migration of glioma cells were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and wound-healing assays. The expression of FOXS1 in glioma cells was analysed by gene microarray, PCR and Western blotting. Then, FOXS1 expression in glioma cells was up- and downregulated by lentivirus transfection, and markers of the epithelial-mesenchymal transformation (EMT) process were detected. Tumour-bearing nude mice were established with different glioma cells and treated with TMZ to measure tumour size, survival time and Ki-67 expression. Finally, the expression of IL-6 in gaMSC subpopulations and its effects on FOXS1 expression in glioma cells were also investigated. Results Conditioned media of gaMSCs promoted the proliferation, migration and chemotherapy resistance of glioma cells. The increased expression of FOXS1 and activation of the EMT process in glioma cells under gaMSC-conditioned media were detected. The relationship of FOXS1, EMT and chemotherapy resistance in glioma cells was demonstrated through the regulation of FOXS1 expression in vitro and in vivo. Moreover, FOXS1 expression in glioma cells was increased by secretion of IL-6 mainly from the CD90low gaMSC subpopulation. Conclusions CD90low gaMSCs could increase FOXS1 expression in glioma cells by IL-6 secretion, thereby activating epithelial-mesenchymal transition and resistance to TMZ in glioma cells. These results indicate a new role of gaMSCs in chemotherapy resistance and provide novel therapeutic targets.

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A novel method for processing adipose-derived stromal stem cells using a closed cell washing concentration device with a hollow fiber membrane module

Biomedical Microdevices ◽

10.1007/s10544-020-00541-0 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Shinji Hayashi ◽

Rieko Yagi ◽

Shuhei Taniguchi ◽

Masami Uji ◽

Hidaka Urano ◽

...

Keyword(s):

Stem Cells ◽

Hollow Fiber ◽

Hollow Fiber Membrane ◽

Membrane Module ◽

Fiber Membrane ◽

Cell Processing ◽

Closed Cell ◽

A Cell ◽

Novel Method ◽

Stromal Stem Cells

AbstractCell-assisted lipotransfer (CAL) is an advanced lipoinjection method that uses autologous lipotransfer with addition of a stromal vascular fraction (SVF) containing adipose-derived stromal stem cells (ASCs). The CAL procedure of manual isolation of cells from fat requires cell processing to be performed in clean environment. To isolate cells from fat without the need for a cell processing center, such as in a procedure in an operation theater, we developed a novel method for processing SVF using a closed cell washing concentration device (CCD) with a hollow fiber membrane module. The CCD consists of a sterilized closed circuit, bags and hollow fiber, semi-automatic device and the device allows removal of >99.97% of collagenase from SVF while maintaining sterility. The number of nucleated cells, ASCs and viability in SVF processed by this method were equivalent to those in SVF processed using conventional manual isolation. Our results suggest that the CCD system is as reliable as manual isolation and may also be useful for CAL. This approach will help in the development of regenerative medicine at clinics without a cell processing center.

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