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 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 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.

scholarly journals Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1536 ◽  
Author(s):  
Norlaily Mohd Ali ◽  
Lily Boo ◽  
Swee Keong Yeap ◽  
Huynh Ky ◽  
Dilan A. Satharasinghe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Culture Condition ◽  
Therapeutic Potential ◽  
Age Groups ◽  
Human Mesenchymal Stem Cells ◽  
Culture Conditions ◽  
Differentiation Potential

Decline in the therapeutic potential of bone marrow-derived mesenchymal stem cells (MSC) is often seen with older donors as compared to young. Although hypoxia is known as an approach to improve the therapeutic potential of MSC in term of cell proliferation and differentiation capacity, its effects on MSC from aged donors have not been well studied. To evaluate the influence of hypoxia on different age groups, MSC from young (<30 years) and aged (>60 years) donors were expanded under hypoxic (5% O2) and normal (20% O2) culture conditions. MSC from old donors exhibited a reduction in proliferation rate and differentiation potential together with the accumulation of senescence features compared to that of young donors. However, MSC cultured under hypoxic condition showed enhanced self-renewing and proliferation capacity in both age groups as compared to normal condition. Bioinformatic analysis of the gene ontology (GO) and KEGG pathway under hypoxic culture condition identified hypoxia-inducible miRNAs that were found to target transcriptional activity leading to enhanced cell proliferation, migration as well as decrease in growth arrest and apoptosis through the activation of multiple signaling pathways. Overall, differentially expressed miRNA provided additional information to describe the biological changes of young and aged MSCs expansion under hypoxic culture condition at the molecular level. Based on our findings, the therapeutic potential hierarchy of MSC according to donor’s age group and culture conditions can be categorized in the following order: young (hypoxia) > young (normoxia) > old aged (hypoxia) > old aged (normoxia).

scholarly journals Therapeutic potential of extracellular vesicles derived from human mesenchymal stem cells in a model of progressive multiple sclerosis

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0202590 ◽  
Author(s):  
Fernando Laso-García ◽  
Jaime Ramos-Cejudo ◽  
Francisco Javier Carrillo-Salinas ◽  
Laura Otero-Ortega ◽  
Ana Feliú ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Human Mesenchymal Stem Cells ◽  
Progressive Multiple Sclerosis

scholarly journals Distinct Immunomodulatory and Migratory Mechanisms Underpin the Therapeutic Potential of Human Mesenchymal Stem Cells in Autoimmune Demyelination

2013 ◽  
Vol 22 (8) ◽  
pp. 1409-1425 ◽  
Author(s):  
Natalie L. Payne ◽  
Guizhi Sun ◽  
Courtney McDonald ◽  
Daniel Layton ◽  
Leon Moussa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Human Mesenchymal Stem Cells ◽  
Autoimmune Demyelination
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