Effects of Human Fibroblast-Derived Extracellular Matrix on Mesenchymal Stem Cells

The mechanical stimulation from extracellular matrix could regulate physiological behavior of cells through the mechanism of mechanotransduction. Previous researches had shown that apoptosis could be regulated by the size of the cell adhesion area.However, the regulation of cell apoptosis by different adhesion shape with the same area is still unclear. This workfocused on the regulation of apoptosis for bone marrow mesenchymal stem cells (MSCs) by different circularity and area of adhesion geometry. We manufactured micro-pattern surface which was suitable for adhesion of MSCs by the technique of micro-contact printing. Three typesof geometry for individual is land of micro-pattern were designed. We adopted terminal-deoxynucleoitidyl transfer as emediated nick end labeling (TUNEL) method to detectcell apoptosis. This research shows that the adhesion geometry which has smaller area and greater circularity will promote apoptosis of MSCs. This indicates that MSCsmay prefer to live on the surface without any restrict. Ourstudies focused on the significantly important problem about interaction between extracellular matrix and physiological behavior of mesenchymal stem cells.

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Patient Heterogeneity in Acute Myeloid Leukemia: Leukemic Cell Communication by Release of Soluble Mediators and Its Effects on Mesenchymal Stem Cells

Diseases ◽

10.3390/diseases9040074 ◽

2021 ◽

Vol 9 (4) ◽

pp. 74

Author(s):

Elise Aasebø ◽

Annette K. Brenner ◽

Maria Hernandez-Valladares ◽

Even Birkeland ◽

Olav Mjaavatten ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Extracellular Matrix ◽

Acute Myeloid Leukemia ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Untreated Control ◽

Myeloid Leukemia ◽

Control Mscs ◽

Acute Myeloid

Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy, and non-leukemic stromal cells (including mesenchymal stem cells, MSCs) are involved in leukemogenesis and show AML-supporting effects. We investigated how constitutive extracellular mediator release by primary human AML cells alters proteomic profiles of normal bone marrow MSCs. An average of 6814 proteins (range 6493−6918 proteins) were quantified for 41 MSC cultures supplemented with AML-cell conditioned medium, whereas an average of 6715 proteins (range 6703−6722) were quantified for untreated control MSCs. The AML effect on global MSC proteomic profiles varied between patients. Hierarchical clustering analysis identified 10 patients (5/10 secondary AML) showing more extensive AML-effects on the MSC proteome, whereas the other 31 patients clustered together with the untreated control MSCs and showed less extensive AML-induced effects. These two patient subsets differed especially with regard to MSC levels of extracellular matrix and mitochondrial/metabolic regulatory proteins. Less than 10% of MSC proteins were significantly altered by the exposure to AML-conditioned media; 301 proteins could only be quantified after exposure to conditioned medium and 201 additional proteins were significantly altered compared with the levels in control samples (153 increased, 48 decreased). The AML-modulated MSC proteins formed several interacting networks mainly reflecting intracellular organellar structure/trafficking but also extracellular matrix/cytokine signaling, and a single small network reflecting altered DNA replication. Our results suggest that targeting of intracellular trafficking and/or intercellular communication is a possible therapeutic strategy in AML.

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Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium induce Bone Regeneration via Endochondral Ossification

Biomedicines ◽

10.3390/biomedicines9101408 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1408

Author(s):

Susumu Horikoshi ◽

Mikihito Kajiya ◽

Souta Motoike ◽

Mai Yoshino ◽

Shin Morimoto ◽

...

Keyword(s):

Stem Cells ◽

Extracellular Matrix ◽

Mesenchymal Stem Cells ◽

Bone Formation ◽

Bone Regeneration ◽

Endochondral Ossification ◽

Healing Process ◽

Early Period ◽

Cartilage Matrix

Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be transplanted into tissue defect site with no artificial scaffold. Importantly, most bone formation in the developing process or fracture healing proceeds via endochondral ossification. Accordingly, this present study investigated whether C-MSCs generated with chondro-inductive medium (CIM) can induce successful bone regeneration and assessed its healing process. Human bone marrow-derived MSCs were cultured with xeno-free/serum-free (XF) growth medium. To obtain C-MSCs, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. The cell clumps, i.e., C-MSCs, were maintained in XF-CIM. C-MSCs generated with XF-CIM showed enlarged round cells, cartilage matrix, and hypertrophic chondrocytes genes elevation in vitro. Transplantation of C-MSCs generated with XF-CIM induced successful bone regeneration in the SCID mouse calvaria defect model. Immunofluorescence staining for human-specific vimentin demonstrated that donor human and host mouse cells cooperatively contributed the bone formation. Besides, the replacement of the cartilage matrix into bone was observed in the early period. These findings suggested that cartilaginous C-MSCs generated with XF-CIM can induce bone regeneration via endochondral ossification.

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