Magnetically levitated mesenchymal stem cell spheroids cultured with a collagen gel maintain phenotype and quiescence

Multicellular spheroids are an established system for three-dimensional cell culture. Spheroids are typically generated using hanging drop or non-adherent culture; however, an emerging technique is to use magnetic levitation. Herein, mesenchymal stem cell spheroids were generated using magnetic nanoparticles and subsequently cultured within a type I collagen gel, with a view towards developing a bone marrow niche environment. Cells were loaded with magnetic nanoparticles, and suspended beneath an external magnet, inducing self-assembly of multicellular spheroids. Cells in spheroids were viable and compared to corresponding monolayer controls, maintained stem cell phenotype and were quiescent. Interestingly, core spheroid necrosis was not observed, even with increasing spheroid size, in contrast to other commonly used spheroid systems. This mesenchymal stem cell spheroid culture presents a potential platform for modelling in vitro bone marrow stem cell niches, elucidating interactions between cells, as well as a useful model for drug delivery studies.

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Proteomic Profiling Identifies Distinct Bone Marrow Niche Mesenchymal Stem Cell Populations In AML Patients

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2015.07.042 ◽

2015 ◽

Vol 15 ◽

pp. S19

Author(s):

Peter P. Ruvolo ◽

Rui-Yu Wang ◽

Vivian Ruvolo ◽

Zhihong Zeng ◽

YiHua Qiu ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cell Populations ◽

Bone Marrow Niche ◽

Proteomic Profiling ◽

Stem Cell Populations

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Laminin-521 Promotes Rat Bone Marrow Mesenchymal Stem Cell Sheet Formation on Light-Induced Cell Sheet Technology

BioMed Research International ◽

10.1155/2017/9474573 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Zhiwei Jiang ◽

Yue Xi ◽

Kaichen Lai ◽

Ying Wang ◽

Huiming Wang ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cell Sheet ◽

Sheet Thickness ◽

Collagen Type I ◽

Type I ◽

Cell Sheets ◽

Cell Sheet Technology ◽

Rat Bone

Rat bone marrow mesenchymal stem cell sheets (rBMSC sheets) are attractive for cell-based tissue engineering. However, methods of culturing rBMSC sheets are critically limited. In order to obtain intact rBMSC sheets, a light-induced cell sheet method was used in this study. TiO2 nanodot films were coated with (TL) or without (TN) laminin-521. We investigated the effects of laminin-521 on rBMSCs during cell sheet culturing. The fabricated rBMSC sheets were subsequently assessed to study cell sheet viability, reattachment ability, cell sheet thickness, collagen type I deposition, and multilineage potential. The results showed that laminin-521 could promote the formation of rBMSC sheets with good viability under hyperconfluent conditions. Cell sheet thickness increased from an initial 26.7 ± 1.5 μm (day 5) up to 47.7 ± 3.0 μm (day 10). Moreover, rBMSC sheets maintained their potential of osteogenic, adipogenic, and chondrogenic differentiation. This study provides a new strategy to obtain rBMSC sheets using light-induced cell sheet technology.

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A novel 3D mesenchymal stem cell model of the multiple myeloma bone marrow niche: biologic and clinical applications

Oncotarget ◽

10.18632/oncotarget.12643 ◽

2016 ◽

Vol 7 (47) ◽

pp. 77326-77341 ◽

Cited By ~ 19

Author(s):

Jana Jakubikova ◽

Danka Cholujova ◽

Teru Hideshima ◽

Paulina Gronesova ◽

Andrea Soltysova ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cell Model ◽

Clinical Applications ◽

Bone Marrow Niche ◽

Stem Cell Model

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Porous matrix nanometric scaffold repairs rabbit tibia injury by promoting bone marrow mesenchymal stem cell osteogenic differentiation and up-regulating type I and II collagen content

Materials Express ◽

10.1166/mex.2021.2025 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1031-1037

Author(s):

Bozan Dong ◽

Dongjie Zhang

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Osteogenic Differentiation ◽

Type Ii Collagen ◽

Porous Matrix ◽

Type I ◽

Model Group ◽

Rabbit Tibia ◽

Collagen Level

To explore the effect of porous matrix nanometer scaffold on Bone marrow mesenchymal stem cell osteogenic differentiation and type I and II collagen content in rabbit tibial injury. 22 rabbits, weighing 2.20–3.10 kg, were equally divided into model and treatment groups. Von Kossa was used to detect osteogenic differentiation, while Western blot detected type I and type II collagen. The bone density meter measurement software was used to assess tibial bone density. Universal material testing machine was used to detect biomechanical indicators level, while HE staining detected bone morphology. Adherent Cells growth were observed in a week; where cells clusters appeared and continued to grow 2 weeks later, and the number of osteoblasts and mineralized nodules increased significantly 3 weeks later. The collagen level in the treatment group was significantly higher than that in model group (P < 0.05). The tibia bone mineral density in model group was significantly lower at the sixth and twelfth weeks after surgery (P < 0.05). The maximum bending load and bending stiffness of model group were significantly lower than those of treatment group with higher damage degree (P < 0.05). Treatment increased the bone tissue and osteoblasts, leading to production of trabecular bone structure. No clustered regenerated bone-like tissues in model group were observed. The porous matrix nanometer scaffold can repair rabbit tibia injury possibly by promoting Bone marrow mesenchymal stem cell osteogenic differentiation and increasing type I and type II collagen level.

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MT1-MMP Regulates Hematopoiesis Through HIF-Mediated Chemo-/Cytokine Release From the Bone Marrow Niche,

Blood ◽

10.1182/blood.v118.21.3409.3409 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3409-3409

Author(s):

Chiemi Nishida ◽

Kaori Kusubata ◽

Yoshihiko Tashiro ◽

Ismael Gritli ◽

Aki Sato ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Cell Fate ◽

Conflicts Of Interest ◽

Stem Cell Differentiation ◽

Cell Phenotype ◽

Bone Marrow Niche ◽

Matrix Remodeling ◽

Hematopoietic Stem

Abstract Abstract 3409 Stem cells reside in a physical niche, a particular microenvironment. The organization of cellular niches has been shown to play a key role in regulating normal stem cell differentiation, stem cell maintenance and regeneration. Various stem cell niches have been shown to be hypoxic, thereby maintaining the stem cell phenotype, e.g. for hematopoietic stem cells (HSCs) or cancer stem cells. The bone marrow (BM) niche is a rich reservoir for tissue-specific pluripotent HSCs. Proteases, such as matrix metalloproteinases (MMPs) can modulate stem cell fate due to their proteolytic or non-proteolytic functions (abilities). We have investigated the role of membrane-type1 matrix metalloproteinase (MT1-MMP), known for its role in pericellular matrix remodeling and cell migration, in hematopoiesis. MT1-MMP is highly expressed in HSCs and stromal cells. In MT1-MMP−/− mice, release of kit ligand (KitL), stromal cell derived factor-1 (SDF-1/CXCL12), erythropoietin (Epo) and interleukin-7 were impaired resulting in erythroid, myeloid and T and B lymphoid differentiation. Addition of exogenous rec. KitL and rec. SDF-1 restored hematopoiesis in vivo and in vitro. Further mechanistic studies revealed that MT1-MMP in a non-proteolytic manner activates the HIF-1 pathway, thereby inducing the transcription of the HIF-responsive genes KitL, SDF-1 and Epo. These results suggested MT1-MMP as a critical regulator of postnatal hematopoiesis, which as a modulator of the HIF pathway alters critical hematopoietic niche factors necessary for terminal differentiation and or migration. Thus, our results indicate that MT1-MMP as a key molecular link between hypoxia and the regulation of vital HSC niche factors. Disclosures: No relevant conflicts of interest to declare.

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