scholarly journals Assessment of the Neuroprotective and Stemness Properties of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells under Variable (5% vs. 21%) Aerobic Conditions

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 717
Author(s):  
Ewelina Tomecka ◽  
Wioletta Lech ◽  
Marzena Zychowicz ◽  
Anna Sarnowska ◽  
Magdalena Murzyn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Atmospheric Oxygen ◽  
Neuroprotective Effect ◽  
Culture Conditions ◽  
Wharton’S Jelly ◽  
Oxygen Level ◽  
Wharton's Jelly ◽  
Cell Based Therapy ◽  
Oxygen Conditions

To optimise the culture conditions for human Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) intended for clinical use, we investigated ten different properties of these cells cultured under 21% (atmospheric) and 5% (physiological normoxia) oxygen concentrations. The obtained results indicate that 5% O2 has beneficial effects on the proliferation rate, clonogenicity, and slowdown of senescence of hWJ-MSCs; however, the oxygen level did not have an influence on the cell morphology, immunophenotype, or neuroprotective effect of the hWJ-MSCs. Nonetheless, the potential to differentiate into adipocytes, osteocytes, and chondrocytes was comparable under both oxygen conditions. However, spontaneous differentiation of hWJ-MSCs into neuronal lineages was observed and enhanced under atmospheric oxygen conditions. The cells relied more on mitochondrial respiration than glycolysis, regardless of the oxygen conditions. Based on these results, we can conclude that hWJ-MSCs could be effectively cultured and prepared under both oxygen conditions for cell-based therapy. However, the 5% oxygen level seemed to create a more balanced and appropriate environment for hWJ-MSCs.

scholarly journals Pressure Stimuli Improve the Proliferation of Wharton’s Jelly-Derived Mesenchymal Stem Cells under Hypoxic Culture Conditions

2020 ◽  
Vol 21 (19) ◽  
pp. 7092
Author(s):  
Sang Eon Park ◽  
Hyeongseop Kim ◽  
Soojin Kwon ◽  
Suk-joo Choi ◽  
Soo-young Oh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Primary Culture ◽  
Therapeutic Efficacy ◽  
Culture Conditions ◽  
Wharton’S Jelly ◽  
Wharton's Jelly ◽  
Accelerated Proliferation ◽  
Apoptotic Effects

Mesenchymal stem cells (MSCs) are safe, and they have good therapeutic efficacy through their paracrine action. However, long-term culture to produce sufficient MSCs for clinical use can result in side-effects, such as an inevitable senescence and the reduction of the therapeutic efficacy of the MSCs. In order to overcome this, the primary culture conditions of the MSCs can be modified to simulate the stem cells’ niche environment, resulting in accelerated proliferation, the achievement of the target production yield at earlier passages, and the improvement of the therapeutic efficacy. We exposed Wharton’s jelly-derived MSCs (WJ-MSCs) to pressure stimuli during the primary culture step. In order to evaluate the proliferation, stemness, and therapeutic efficacy of WJ-MSCs, image, genetic, and Western blot analyses were carried out. Compared with standard incubation culture conditions, the cell proliferation was significantly improved when the WJ-MSCs were exposed to pressure stimuli. However, the therapeutic efficacy (the promotion of cell proliferation and anti-apoptotic effects) and the stemness of the WJ-MSCs was maintained, regardless of the culture conditions. Exposure to pressure stimuli is a simple and efficient way to improve WJ-MSC proliferation without causing changes in stemness and therapeutic efficacy. In this way, clinical-grade WJ-MSCs can be produced rapidly and used for therapeutic applications.

scholarly journals Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Wioletta Lech ◽  
Anna Sarnowska ◽  
Zuzanna Kuczynska ◽  
Filip Dabrowski ◽  
Anna Figiel-Dabrowska ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ex Vivo ◽  
Neuroprotective Effect ◽  
Hippocampal Slices ◽  
Wharton’S Jelly ◽  
Trophic Factors ◽  
Differentiation Markers ◽  
Wharton's Jelly

Abstract Tuning stem cells microenvironment in vitro may influence their regenerative properties. In this study Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) were encapsulated in 3D hydrogels derived from human fibrin (FB) or platelet lysate (PL) and the oxygen level was adjusted to physiological normoxia (5% O2). The influence of the type of the scaffold and physiological normoxia conditions was tested on the WJ-MSCs' survivability, proliferation, migratory potential, the level of expression of selected trophic factors, cytokines, and neural markers. Encapsulated WJ-MSCs revealed high survivability, stable proliferation rate, and ability to migrate out of the hydrogel and the up-regulated expression of all tested factors, as well as the increased expression of neural differentiation markers. Physiological normoxia stimulated proliferation of encapsulated WJ-MSCs and significantly enhanced their neuronal, but not glial, differentiation. Ex vivo studies with indirect co-culture of organotypic hippocampal slices and cell-hydrogel bio-constructs revealed strong neuroprotective effect of WJ-MSCs against neuronal death in the CA1 region of the rat hippocampus. This effect was potentiated further by FB scaffolds under 5% O2 conditions. Our results indicating significant effect of oxygen and 3D cytoarchitecture suggest the urgent need for further optimization of the microenvironmental conditions to improve therapeutical competence of the WJ-MSCs population.

scholarly journals Immunomodulatory Properties of Wharton’s Jelly-Derived Mesenchymal Stem Cells from Three Anatomical Segments of Umbilical Cord

2021 ◽  
Vol 50 (6) ◽  
pp. 1715-1726
Author(s):  
Jezamine Lim ◽  
Sue Ping Eng ◽  
Wei Yen Yeoh ◽  
Yik Wan Low ◽  
Nur Mohd Shafwan bin Jusoh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Lymphocyte Proliferation ◽  
Mononuclear Cells ◽  
Wharton’S Jelly ◽  
Wharton's Jelly ◽  
Cell Based Therapy ◽  
Hla Dr ◽  
Significant Difference

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that are reported to be immune-privileged and immune-evasive. MSCs are capable of differentiating into specific cell types for subsequent use in cell-based therapy. They express low levels of human leucocyte antigen (HLA)-ABC and no HLA-DR. Wharton’s jelly-derived MSCs (WJ-MSCs) were also found to express human leukocyte antigen G (HLA-G), which renders them immunosuppressive. This study aimed to determine whether cultured WJ-MSCs retain their immune-privileged and immune-evasive properties after cell differentiation, and whether these properties differ among MSCs derived from different anatomical segments of the umbilical cord. Umbilical cords of healthy pregnant mothers undergoing caesarean section were obtained and grouped by three anatomical segments: fetal, middle, and maternal segments. WJ-MSCs were isolated, culture-expanded, and differentiated into osteogenic cells. Expression of HLA-DR, HLA-ABC, and HLA-G were quantified using flow cytometry. Both undifferentiated and osteodifferentiated WJ-MSCs were subsequently co-cultured with allogeneic peripheral blood mononuclear cells with/without lipopolysaccharide (LPS) stimulation for five days. Lymphocyte proliferation assay was performed using carboxyfluorescein succinimidyl ester (CFSE) as a tracker. Our results showed no significant difference existed in the HLA profiles among WJ-MSCs from different segments and between WJ-MSCs with and without osteogenic differentiation. Mean levels for HLA-G, HLABC, and HLA-DR were 24.82±17.64, 52.50±18.41, and 1.00±1.68%, respectively. Stimulation with LPS and WJ-MSCs increased peripheral blooc mononuclear cells (PBMC) proliferation. However, PBMC proliferation was significantly lower when PBMCs were co-cultured with osteodifferentiated WJ-MSCs (p < .05; with LPS stimulation and p < .001 without LPS stimulation) than when they were co-cultured with undifferentiated WJ-MSCs. These findings suggest that cultured WJ-MSCs stimulate lymphocyte proliferation and are not immune-privileged. Osteodifferentiated WJ-MSCs reduced the immunogenicity of WJ-MSCs, and this reduction in PBMC proliferation was even more pronounced in the presence of LPS (p < .05). In conclusion, cultured WJ-MSCs are not immune-privileged. Osteodifferentiated WJ-MSCs are less immunogenic than undifferentiated WJ-MSCs, in which case hypoimmunogenicity is more profound under LPS-stimulated conditions.

scholarly journals Enhanced Hepatogenic Differentiation of Human Wharton’s Jelly–Derived Mesenchymal Stem Cells by Using Three-Step Protocol

2019 ◽  
Vol 20 (12) ◽  
pp. 3016 ◽  
Author(s):  
Wachira Panta ◽  
Sumeth Imsoonthornruksa ◽  
Ton Yoisungnern ◽  
Sanong Suksaweang ◽  
Mariena Ketudat-Cairns ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Glycogen Storage ◽  
Wharton’S Jelly ◽  
Wharton's Jelly ◽  
Lineage Differentiation ◽  
Cell Based Therapy ◽  
Hepatogenic Differentiation ◽  
Pre Treatment

Currently, human Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) are an attractive source of stem cells for cell-based therapy, owing to their ability to undergo self-renewal and differentiate into all mesodermal, some neuroectodermal, and endodermal progenies, including hepatocytes. Herein, this study aimed to investigate the effects of sodium butyrate (NaBu), an epigenetic regulator that directly inhibits histone deacetylase, on hepatic endodermal lineage differentiation of hWJ-MSCs. NaBu, at 1 mM, optimally promoted endodermal differentiation of hWJ-MSCs, along with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) supplementation (EGF + bFGF + 1 mM NaBu). CXCR4, HNF3β, SOX17 (endodermal), and GATA6 (mesendodermal) mRNAs were also up-regulated (p < 0.001). Immunocytochemistry and a Western blot analysis of SOX17 and HNF3β confirmed that the EGF + bFGF + 1 mM NaBu condition was appropriately pre-treated with hWJ-MSCs before hepatogenic differentiation. Furthermore, the hepatogenic medium + NaBu pre-treatment up-regulated hepatoblast (AFP and HNF3β) and hepatic (CK18 and ALB) markers, and increased the proportion of mature hepatocyte functions, including G6P, C/EBPα, and CYP2B6 mRNAs, glycogen storage and urea secretion. The hepatogenic medium + NaBu in the pre-treatment step can induce hWJ-MSC differentiation toward endodermal, hepatoblastic, and hepatic lineages. Therefore, the hepatogenic medium + NaBu pre-treatment for differentiating hWJ-MSCs could represent an alternative protocol for cell-based therapy and drug screening in clinical applications.

scholarly journals Regenerative Potential of the Product “CardioCell” Derived from the Wharton’s Jelly Mesenchymal Stem Cells for Treating Hindlimb Ischemia

2019 ◽  
Vol 20 (18) ◽  
pp. 4632 ◽  
Author(s):  
Musiał-Wysocka ◽  
Kot ◽  
Sułkowski ◽  
Majka
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Wharton’S Jelly ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Hindlimb Ischemia ◽  
Wharton's Jelly ◽  
Cell Based Therapy ◽  
Therapeutic Benefits

In recent years, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality in regenerative medicine. They hold great promise for treating civilization-wide diseases, including cardiovascular diseases, such as acute myocardial infarction and critical limb ischemia. MSCs isolated from Wharton’s jelly (WJ-MSCs) may be utilized in both cell-based therapy and vascular graft engineering to restore vascular function, thereby providing therapeutic benefits for patients. The efficacy of WJ-MSCs lies in their multipotent differentiation ability toward vascular smooth muscle cells, endothelial cells and other cell types, as well as their capacity to secrete various trophic factors, which are potent in promoting angiogenesis, inhibiting apoptosis and modulating immunoreaction. Ischemic limb disease is caused by insufficient nutrient and oxygen supplies resulting from damaged peripheral arteries. The lack of nutrients and oxygen causes severe tissue damage in the limb, thereby resulting in severe morbidities and mortality. The therapeutic effects of the conventional treatments are still not sufficient. Cell transplantations in small animal model (mice) are vital for deciphering the mechanisms of MSCs’ action in muscle regeneration. The stimulation of angiogenesis is a promising strategy for the treatment of ischemic limbs, restoring blood supply for the ischemic region. In the present study, we focus on the therapeutic properties of the human WJ-MSCs derived product, Cardio. We investigated the role of CardioCell in promoting angiogenesis and relieving hindlimb ischemia. Our results confirm the healing effect of CardioCell and strongly support the use of the WJ-MSCs in regenerative medicine.

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