Microwell Geometry Modulates Interleukin-6 Secretion in Human Mesenchymal Stem Cells

MRS Advances ◽  
2017 ◽  
Vol 2 (47) ◽  
pp. 2561-2570
Author(s):  
Xun Xu ◽  
Weiwei Wang ◽  
Zhengdong Li ◽  
Karl Kratz ◽  
Nan Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Interleukin 6 ◽  
Therapeutic Potential ◽  
Chemical Properties ◽  
Human Mesenchymal Stem Cells ◽  
Secretion Profile ◽  
Highly Sensitive ◽  
Physical And Chemical ◽  
Cell Culture Substrate

ABSTRACTThe therapeutic effect of mesenchymal stem cells (MSCs) has been investigated in various clinical applications, in which their functional benefits are mainly attributed to the secretion of soluble factors. The enhancement of their therapeutic potential by physical and chemical properties of cell culture substrate is a safe and effective strategy, since they are highly sensitive to their microenvironment such as the elasticity and surface topography. In this study, we demonstrated that the geometry of polymeric substrate regulated the interleukin-6 (IL-6) secretion of human adipose derived MSCs. Polystyrene substrates comprising arrays of square-shaped (S50) or round-shaped (R50) microwells (side length or diameter of 50 μm and depth of 10 μm) were prepared by injection molding. Cellular apoptototic rate of MSCs was not affected by the microwell geometry, while the upregulated secretion of IL-6 and the enhancement of nuclear transcription factor STAT3 were detected in MSCs seeded on S50 substrate. The geometry-dependent modulatory effect was highly associated with ROCK signaling cascade. The inhibition of ROCK abolished the disparity in IL-6 secretion. These findings highlight the possibility to steer the secretion profile of stem cells via microwell geometry in combination with the manipulation of ROCK signaling pathway.

Integrin β1 activation by micro-scale curvature promotes pro-angiogenic secretion of human mesenchymal stem cells

2017 ◽  
Vol 5 (35) ◽  
pp. 7415-7425 ◽  
Author(s):  
Zhengdong Li ◽  
Weiwei Wang ◽  
Xun Xu ◽  
Karl Kratz ◽  
Jie Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Β1 Integrin ◽  
Integrin Β1 ◽  
Micro Scale ◽  
Culture Substrate ◽  
A Cell ◽  
Scale Surface ◽  
Cell Culture Substrate

A cell culture substrate with micro-scale surface curvature promotes β1 integrin activation and pro-angiogenic secretion of mesenchymal stem cells.

scholarly journals Ex VivoExpansion of Human Mesenchymal Stem Cells in Defined Serum-Free Media

2012 ◽  
Vol 2012 ◽  
pp. 1-21 ◽  
Author(s):  
Sunghoon Jung ◽  
Krishna M. Panchalingam ◽  
Lawrence Rosenberg ◽  
Leo A. Behie
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Culture Media ◽  
Human Mesenchymal Stem Cells ◽  
Efficient Production ◽  
Serum Free ◽  
Medium Development ◽  
Current Cell ◽  
Free Media

Human mesenchymal stem cells (hMSCs) are presently being evaluated for their therapeutic potential in clinical studies to treat various diseases, disorders, and injuries. To date, early-phase studies have indicated that the use of both autologous and allogeneic hMSCs appear to be safe; however, efficacy has not been demonstrated in recent late-stage clinical trials. Optimized cell bioprocessing protocols may enhance the efficacy as well as safety of hMSC therapeutics. Classical media used for generating hMSCs are typically supplemented with ill-defined supplements such as fetal bovine serum (FBS) or human-sourced alternatives. Ideally, culture media are desired to have well-defined serum-free formulations that support the efficient production of hMSCs while maintaining their therapeutic and differentiation capacity. Towards this objective, we review here current cell culture media for hMSCs and discuss medium development strategies.

scholarly journals Analyzing Metabolic States of Adipogenic and Osteogenic Differentiation in Human Mesenchymal Stem Cells via Genome Scale Metabolic Model Reconstruction

2021 ◽  
Vol 9 ◽  
Author(s):  
Thora Bjorg Sigmarsdottir ◽  
Sarah McGarrity ◽  
James T. Yurkovich ◽  
Óttar Rolfsson ◽  
Ólafur Eysteinn Sigurjónsson
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Cell Lineage ◽  
Human Mesenchymal Stem Cells ◽  
Metabolic Model ◽  
Metabolic Function ◽  
Metabolic States ◽  
Initial Discovery ◽  
Genome Scale

Since their initial discovery in 1976, mesenchymal stem cells (MSCs) have been gathering interest as a possible tool to further the development and enhancement of various therapeutics within regenerative medicine. However, our current understanding of both metabolic function and existing differences within the varying cell lineages (e.g., cells in either osteogenesis or adipogenesis) is severely lacking making it more difficult to fully realize the therapeutic potential of MSCs. Here, we reconstruct the MSC metabolic network to understand the activity of various metabolic pathways and compare their usage under different conditions and use these models to perform experimental design. We present three new genome-scale metabolic models (GEMs) each representing a different MSC lineage (proliferation, osteogenesis, and adipogenesis) that are biologically feasible and have distinctive cell lineage characteristics that can be used to explore metabolic function and increase our understanding of these phenotypes. We present the most distinctive differences between these lineages when it comes to enriched metabolic subsystems and propose a possible osteogenic enhancer. Taken together, we hope these mechanistic models will aid in the understanding and therapeutic potential of MSCs.

scholarly journals Contribution of the Interleukin-6/STAT-3 Signaling Pathway to Chondrogenic Differentiation of Human Mesenchymal Stem Cells

2015 ◽  
Vol 67 (5) ◽  
pp. 1250-1260 ◽  
Author(s):  
Masahiro Kondo ◽  
Kunihiro Yamaoka ◽  
Kei Sakata ◽  
Koshiro Sonomoto ◽  
Lin Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Interleukin 6 ◽  
Chondrogenic Differentiation ◽  
Human Mesenchymal Stem Cells

scholarly journals Retinal Lineage Therapeutic Specific Effect of Human Orbital and Abdominal Adipose-Derived Mesenchymal Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Bryan Krief ◽  
Shira Weisthal Algor ◽  
Itay Nakdimon ◽  
Ayala Elhikis ◽  
Moshe Benhamou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Retinal Degeneration ◽  
Therapeutic Potential ◽  
Subcutaneous Fat ◽  
Human Mesenchymal Stem Cells ◽  
Specific Effect ◽  
Photoreceptor Layer ◽  
Retinal Tissue ◽  
Embryonic Origin

Retinal degenerative diseases are one of the main causes of complete blindness in aged population. In this study, we compared the therapeutic potential for retinal degeneration of human mesenchymal stem cells derived from abdominal subcutaneous fat (ABASCs) or from orbital fat (OASCs) due to their accessibility and mutual embryonic origin with retinal tissue, respectively. OASCs were found to protect RPE cells from cell death and were demonstrated to increase early RPE precursor markers, while ABASCs showed a raise in retinal precursor marker expression. Subretinal transplantation of OASCs in a mouse model of retinal degeneration led to restoration of the RPE layer while transplantation of ABASCs resulted in a significant restoration of the photoreceptor layer. Taken together, we demonstrated a lineage-specific therapeutic effect for either OASCs or ABASCs in retinal regeneration.

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