scholarly journals Molecular Mechanisms Involved in Neural Substructure Development during Phosphodiesterase Inhibitor Treatment of Mesenchymal Stem Cells

2020 ◽  
Vol 21 (14) ◽  
pp. 4867
Author(s):  
Jerome Fajardo ◽  
Bruce K. Milthorpe ◽  
Jerran Santos
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Kinase ◽  
Neural Differentiation ◽  
Molecular Mechanisms ◽  
Phosphodiesterase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
High Yield ◽  
Strong Basis ◽  
Cord Injury

Stem cells are highly important in biology due to their unique innate ability to self-renew and differentiate into other specialised cells. In a neurological context, treating major injuries such as traumatic brain injury, spinal cord injury and stroke is a strong basis for research in this area. Mesenchymal stem cells (MSC) are a strong candidate because of their accessibility, compatibility if autologous, high yield and multipotency with a potential to generate neural cells. With the use of small-molecule chemicals, the neural induction of stem cells may occur within minutes or hours. Isobutylmethyl xanthine (IBMX) has been widely used in cocktails to induce neural differentiation. However, the key molecular mechanisms it instigates in the process are largely unknown. In this study we showed that IBMX-treated mesenchymal stem cells induced differentiation within 24 h with the unique expression of several key proteins such as Adapter protein crk, hypoxanthine-guanine phosphoribosyltransferase, DNA topoisomerase 2-beta and Cell division protein kinase 5 (CDK5), vital in linking signalling pathways. Furthermore, the increased expression of basic fibroblast growth factor in treated cells promotes phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) cascades and GTPase–Hras interactions. Bioinformatic and pathway analyses revealed upregulation in expression and an increase in the number of proteins with biological ontologies related to neural development and substructure formation. These findings enhance the understanding of the utility of IBMX in MSC neural differentiation and its involvement in neurite substructure development.

scholarly journals Enhancing the Therapeutic Potential of Mesenchymal Stem Cells with Light-Emitting Diode: Implications and Molecular Mechanisms

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Barbara Sampaio Dias Martins Mansano ◽  
Vitor Pocani da Rocha ◽  
Ednei Luiz Antonio ◽  
Daniele Fernanda Peron ◽  
Rafael do Nascimento de Lima ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Light Emitting Diode ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Light Emitting ◽  
Report Quality

This study evaluated the effects of light-emitting diode (LED) on mesenchymal stem cells (MSCs). An electronic search was conducted in PubMed/MEDLINE, Scopus, and Web of Science database for articles published from 1980 to February 2020. Ten articles met the search criteria and were included in this review. The risk of bias was evaluated to report quality, safety, and environmental standards. MSCs were derived from adipose tissue, bone marrow, dental pulp, gingiva, and umbilical cord. Protocols for cellular irradiation used red and blue light spectrum with variations of the parameters. The LED has been shown to induce greater cellular viability, proliferation, differentiation, and secretion of growth factors. The set of information available leads to proposing a complex signaling cascade for the action of photobiomodulation, including angiogenic factors, singlet oxygen, mitogen-activated protein kinase/extracellular signal-regulated protein kinase, Janus kinase/signal transducer, and reactive oxygen species. In conclusion, although our results suggest that LED can boost MSCs, a nonuniformity in the experimental protocol, bias, and the limited number of studies reduces the power of systematic review. Further research is essential to find the optimal LED irradiation parameters to boost MSCs function and evaluate its impact in the clinical setting.

Dual-enzymatically cross-linked gelatin hydrogel enhances neural differentiation of human umbilical cord mesenchymal stem cells and functional recovery in experimental murine spinal cord injury

2021 ◽  
Author(s):  
Minghao Yao ◽  
Jinrui Li ◽  
Junni Zhang ◽  
Shanshan Ma ◽  
Luyu Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Neuronal Differentiation ◽  
Functional Recovery ◽  
Neural Differentiation ◽  
Human Umbilical Cord ◽  
Gelatin Hydrogel ◽  
Cord Injury

A dual-enzymatically cross-linked gelatin hydrogel is proposed to undergo direct neuronal differentiation of hUC-MSCs for promoting regeneration of spinal cord injury mice.

scholarly journals Pleiotropic effects of Erythropoietin. Influence of Erythropoietin on processes of mesenchymal stem cells differentiation

2019 ◽  
Vol 5 (1) ◽  
pp. 53-66
Author(s):  
Ekaterina V. Zubareva ◽  
Sergey V. Nadezhdin ◽  
Yuriy E. Burda ◽  
Natalia A. Nadezhdina ◽  
Anastasia S. Gashevskaya
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Kinase ◽  
Bone Tissue ◽  
Protective Factor ◽  
Mitogen Activated Protein Kinase ◽  
Recombinant Erythropoietin ◽  
Glycoprotein Hormone ◽  
Hematopoietic Stem ◽  
Erythroid Precursor

Structure and synthesis of Erythropoietin: Erythropoietin (EPO) is a glycoprotein hormone.Recombinant Erythropoietin (Epoetin): Human recombinant erythropoietin is characterised as a factor which stimulates differentiation and proliferation of erythroid precursor cells, and as a tissue protective factor.Anti-ischemic effects of recombinant Erythropoietin: Erythropoietin is one of the most perspective humoral agents which are involved in the preconditioning phenomenon.Erythropoietin receptors and signal transduction pathways: Erythropoietin effects on cells through their interconnection with erythropoietin receptors, which triggers complex intracellular signal cascades, such as JAK2/STAT signaling pathway, phosphatidylinositol 3-kinase (PI3K), protein kinase C, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB signaling pathways.Mechanisms of the effect of Erythropoietin on hematopoietic and non-hematopoietic cells and tissues: In addition to regulation of haemopoiesis, erythropoietin mediates bone formation as it has an effect on hematopoietic stem cells and osteoblastic niche, and this illustrates connection between the processes of haematopoiesis and osteopoiesis which take place in the red bone marrow.The effect of Erythropoietin on mesenchymal stem cells and process of bone tissue formation: Erythropoietin promotes mesenchymal stem cells proliferation, migration and differentiation in osteogenic direction. The evidence of which is expression of bone phenotype by cells under the influence of EPO, including activation of bone specific transcription factors Runx2, osteocalcin and bone sialoprotein.Conclusion: Erythropoietin has a pleiotropic effect on various types of cells and tissues. But the mechanisms which are involved in the process of bone tissue restoration via erythropoietin are still poorly understood.

Valproic acid, A Potential Inducer of Osteogenesis in Mouse Mesenchymal Stem Cells

2020 ◽  
Vol 14 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Narayanan Akshaya ◽  
Prakash Prasith ◽  
Balakrishnan Abinaya ◽  
Badrinath Ashwin ◽  
S.V. Chandran ◽  
...  
Keyword(s):  
Stem Cells ◽  
Valproic Acid ◽  
Mesenchymal Stem Cells ◽  
Osteoblast Differentiation ◽  
Molecular Mechanisms ◽  
Cellular Level ◽  
Mitogen Activated Protein Kinase ◽  
Marker Genes ◽  
Herbaceous Plant ◽  
Alizarin Red

Background: Recent reports have unveiled the potential of flavonoids to enhance bone formation and assuage bone resorption due to their involvement in cell signaling pathways. They also act as an effective alternative to circumvent the disadvantages associated with existing treatment methods, which has increased their scope in orthopedic research. Valproic acid (VA, 2-propylpentanoic acid) is one such flavonoid, obtained from an herbaceous plant, used in the treatment of epilepsy and various types of seizures. Objective: In this study, the role of VA in osteogenesis and the molecular mechanisms underpinning its action in mouse mesenchymal stem cells (mMSCs) were determined. Methods & Results: Cytotoxic studies validated VA’s amiable nature in mMSCs. Alizarin red and von Kossa staining results showed an increased deposition of calcium phosphate in VA-treated mMSCs, which confirmed the occurrence of osteoblast differentiation and mineralization at a cellular level. At the molecular level, there were increased levels of expression of Runx2, a vital bone transcription factor, and other major osteoblast differentiation marker genes in the VAtreated mMSCs. Further, VA-treatment in mMSCs upregulated mir-21 and activated the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway, which might be essential for the expression/activity of Runx2. Conclusion: Thus, the current study confirmed the osteoinductive nature of VA at the cellular and molecular levels, opening the possibility for its application in bone therapeutics with mir-21.

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