scholarly journals Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 619 ◽  
Author(s):  
Jerran Santos ◽  
Thibaut Hubert ◽  
Bruce K Milthorpe

Regenerative medicine is a rapidly expanding area in research and clinical applications. Therapies involving the use of small molecule chemicals aim to simplify the creation of specific drugs for clinical applications. Adult mesenchymal stem cells have recently shown the capacity to differentiate into several cell types applicable for regenerative medicine (specifically neural cells, using chemicals). Valproic acid was an ideal candidate due to its clinical stability. It has been implicated in the induction of neural differentiation; however, the mechanism and the downstream events were not known. In this study, we showed that using valproic acid on adult mesenchymal stem cells induced neural differentiation within 24 h by upregulating the expression of suppressor of cytokine signaling 5 (SOCS5) and Fibroblast growth factor 21 (FGF21), without increasing the potential death rate of the cells. Through this, the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is downregulated, and the mitogen-activated protein kinase (MAPK) cascade is activated. The bioinformatics analyses revealed the expression of several neuro-specific proteins as well as a range of functional and structural proteins involved in the formation and development of the neural cells.

2018 ◽  
Vol 18 (3) ◽  
pp. 264 ◽  
Author(s):  
Roberto Berebichez-Fridman ◽  
Pablo R. Montero-Olvera

First discovered by Friedenstein in 1976, mesenchymal stem cells (MSCs) are adult stem cells found throughout the body that share a fixed set of characteristics. Discovered initially in the bone marrow, this cell source is considered the gold standard for clinical research, although various other sources—including adipose tissue, dental pulp, mobilised peripheral blood and birth-derived tissues—have since been identified. Although similar, MSCs derived from different sources possess distinct characteristics, advantages and disadvantages, including their differentiation potential and proliferation capacity, which influence their applicability. Hence, they may be used for specific clinical applications in the fields of regenerative medicine and tissue engineering. This review article summarises current knowledge regarding the various sources, characteristics and therapeutic applications of MSCs.Keywords: Mesenchymal Stem Cells; Adult Stem Cells; Regenerative Medicine; Cell Differentiation; Tissue Engineering.


2019 ◽  
Vol 9 (3) ◽  
pp. 497-504 ◽  
Author(s):  
Homa Salami ◽  
Seyed Javad Mowal ◽  
Rasoul Moukhah ◽  
Zahra Hajebrahimi ◽  
Seyed Abdolhakim Hosseini ◽  
...  

Purpose: The histone deacetylases (HDAC) inhibitor, valproic acid (VPA), is a common antiepileptic drug and is attractive for its broad range of therapeutic effects on many diseases. It has been employed as an inducer of pluripotency in some cultured cells. Conversely, VPA has also been employed as an inducer of in vitro differentiation in many other cells. Therefore, we employed WJMSCs as a cellular target to evaluate the differential effects of of VPA on potency state and differentiation level of Wharton’s Jelly mesenchymal stem cells (WJMSCs) in various concentrations and different culture mediums. Methods: The isolated WJMSCs were cultured in DMEM (MSC medium). According to previous protocols, WJMSCs were treated with 0, 0.5 and 1 mM VPA in MSC or embryonic stem cell (ESC) medium and 2 mM VPA in neural differentiation medium. Real-time polymerase chain reaction (PCR) and western blot analysis were performed for evaluating the expression of pluripotency markers. MTT and caspase assays were also performed on VPA-treated cells. Results: The expression of pluripotency markers and the viability of the WJMSCs – determined by MTT assay – were significantly increased after 0.5 mM VPA treatment in ESC medium. A 2 mM VPA treatment in neural differentiation medium significantly diminished the expression of pluripotency markers and the viability of WJMSCs. Conclusion: According to our results, both VPA concentration and the medium context can influence VPA effects on WJMSCs. The differential effects of VPA on WJMSCs can reflect its wide range of effects in the treatment of various diseases.


Author(s):  
Seyed Mehdi Hoseini ◽  
Maryam Moghaddam-Matin ◽  
Ahmad Reza Bahrami ◽  
Fateme Montazeri ◽  
Seyed Mehdi Kalantar

Introduction: Amniotic fluid contains a mixture of different cell types sloughed from the fetal skin, respiratory, alimentary and urogenital tracts, as well as the amnion membrane. As amniotic fluid develops prior to the process of gastrulation, many cells found in its heterogeneous population do not undergo lineage specialization. Therefore, amniotic fluid-derived mesenchymal stem cells (AF-MSCs) may correspond to a new class of stem cells with properties of intermediate plasticity between pluripotent and adult stem cell types. Compared to mesenchymal stem cells (MSCs) from other sources, such as bone marrow, AF-MSCs have better properties for clinical applications, such as differentiation into the cells of three germ layers, high clonal capacity, ability to form embryoid bodies, expression of pluripotent markers, high self-renewal capacity (over 250 population doublings) with normal karyotype at late passages, long telomere length due to continued telomerase activity, specially non-tumorigenicity, low immunogenicity, anti-inflammatory and immunomodulatory properties. Conclusion: Such features have nominated AF-MSC for a range of clinical applications, including in regenerative medicine. In several studies, these cells have been used to regenerate nerve, lung, and heart tissues. Overall, AF-MSCs are expected to be an ideal source of stem cells for future regenerative medicine and tissue engineering.


Life Sciences ◽  
2020 ◽  
Vol 256 ◽  
pp. 118002 ◽  
Author(s):  
Maria Maqsood ◽  
Mingzhu Kang ◽  
Xiaotao Wu ◽  
Jinghua Chen ◽  
Liping Teng ◽  
...  

Author(s):  
Martina Trávníčková ◽  
Lucie Bačáková

Tissue engineering is a very promising field of regenerative medicine. Life expectancy has been increasing, and tissue replacement is increasingly needed in patients suffering from various degenerative disorders of the organs. The use of adult mesenchymal stem cells (e.g. from adipose tissue or from bone marrow) in tissue engineering seems to be a promising approach for tissue replacements. Clinical applications can make direct use of the large secretome of these cells, which can have a positive influence on other cells around. Another advantage of adult mesenchymal stem cells is the possibility to differentiate them into various mature cells via appropriate culture conditions (i.e. medium composition, biomaterial properties, and dynamic conditions). This review is focused on current and future ways to carry out tissue replacement of damaged bones and blood vessels, especially with the use of suitable adult mesenchymal stem cells as a potential source of differentiated mature cells that can later be used for tissue replacement. The advantages and disadvantages of different stem cell sources are discussed, with a main focus on adipose-derived stem cells. Patient factors that can influence later clinical applications are taken into account.


2019 ◽  
Vol 20 (5) ◽  
pp. 1132 ◽  
Author(s):  
Yoichi Yamada ◽  
Sayaka Nakamura-Yamada ◽  
Kaoru Kusano ◽  
Shunsuke Baba

Dental pulp stem cells (DPSCs) are mesenchymal stem cells (MSCs) that have multipotent differentiation and a self-renewal ability. They have been useful not only for dental diseases, but also for systemic diseases. Extensive studies have suggested that DPSCs are effective for various diseases, such as spinal cord injuries, Parkinson’s disease, Alzheimer’s disease, cerebral ischemia, myocardial infarction, muscular dystrophy, diabetes, liver diseases, eye diseases, immune diseases, and oral diseases. DPSCs have the potential for use in a cell-therapeutic paradigm shift to treat these diseases. It has also been reported that DPSCs have higher regenerative potential than the bone marrow-derived mesenchymal stem cells known as representative MSCs. Therefore, DPSCs have recently gathered much attention. In this review, the therapeutic potential of DPSCs, the latest progress in the pre-clinical study for treatment of these various systemic diseases, and the clinical applications of DPSCs in regenerative medicine, are all summarized. Although challenges, including mechanisms of the effects and establishment of cell processing and transplantation methods for clinical use, still remain, DPSCs could be promising stem cells sources for various clinical applications, because of their easy isolation by a noninvasive procedure without ethical concerns.


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