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.

scholarly journals Wharton’s Jelly Derived Mesenchymal Stem Cells: Future of Regenerative Medicine? Recent Findings and Clinical Significance

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Ilona Kalaszczynska ◽  
Katarzyna Ferdyn
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Adult Stem Cells ◽  
Wharton’S Jelly ◽  
Therapeutic Effects ◽  
Ethical Concerns ◽  
Wharton's Jelly ◽  
Privileged Status ◽  
Therapeutic Properties

Around 5 million annual births in EU and 131 million worldwide give a unique opportunity to collect lifesaving Wharton’s jelly derived mesenchymal stem cells (WJ-MSC). Evidences that these cells possess therapeutic properties are constantly accumulating. Collection of WJ-MSC is done at the time of delivery and it is easy and devoid of side effects associated with collection of adult stem cells from bone marrow or adipose tissue. Likewise, their rate of proliferation, immune privileged status, lack of ethical concerns, nontumorigenic properties make them ideal for both autologous and allogeneic use in regenerative medicine applications. This review provides an outline of the recent findings related to WJ-MSC therapeutic effects and possible advantage they possess over MSC from other sources. Results of first clinical trials conducted to treat immune disorders are highlighted.

scholarly journals Anti-Fibrotic Effect of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells on Skeletal Muscle Cells, Mediated by Secretion of MMP-1

2020 ◽  
Vol 21 (17) ◽  
pp. 6269
Author(s):  
Alee Choi ◽  
Sang Eon Park ◽  
Jang Bin Jeong ◽  
Suk-joo Choi ◽  
Soo-young Oh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wharton’S Jelly ◽  
Mdx Mice ◽  
Therapeutic Effects ◽  
Paracrine Factors ◽  
Wharton's Jelly ◽  
Muscle Fibrosis ◽  
Skeletal Muscle Fibrosis

Extracellular matrix (ECM) components play an important role in maintaining skeletal muscle function, but excessive accumulation of ECM components interferes with skeletal muscle regeneration after injury, eventually inducing fibrosis. Increased oxidative stress level caused by dystrophin deficiency is a key factor in fibrosis in Duchenne muscular dystrophy (DMD) patients. Mesenchymal stem cells (MSCs) are considered a promising therapeutic agent for various diseases involving fibrosis. In particular, the paracrine factors secreted by MSCs play an important role in the therapeutic effects of MSCs. In this study, we investigated the effects of MSCs on skeletal muscle fibrosis. In 2–5-month-old mdx mice intravenously injected with 1 × 105 Wharton’s jelly (WJ)-derived MSCs (WJ-MSCs), fibrosis intensity and accumulation of calcium/necrotic fibers were significantly decreased. To elucidate the mechanism of this effect, we verified the effect of WJ-MSCs in a hydrogen peroxide-induced fibrosis myotubes model. In addition, we demonstrated that matrix metalloproteinase-1 (MMP-1), a paracrine factor, is critical for this anti-fibrotic effect of WJ-MSCs. These findings demonstrate that WJ-MSCs exert anti-fibrotic effects against skeletal muscle fibrosis, primarily via MMP-1, indicating a novel target for the treatment of muscle diseases, such as DMD.

scholarly journals Evaluating the Differential Effects of Valproic Acid on Wharton’s Jelly Mesenchymal Stem Cells

2019 ◽  
Vol 9 (3) ◽  
pp. 497-504 ◽  
Author(s):  
Homa Salami ◽  
Seyed Javad Mowal ◽  
Rasoul Moukhah ◽  
Zahra Hajebrahimi ◽  
Seyed Abdolhakim Hosseini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Valproic Acid ◽  
Mesenchymal Stem Cells ◽  
Neural Differentiation ◽  
Wharton’S Jelly ◽  
Therapeutic Effects ◽  
Differential Effects ◽  
Wharton's Jelly ◽  
Differentiation Medium ◽  
Pluripotency Markers

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.

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 Human Wharton’s Jelly—Cellular Specificity, Stemness Potency, Animal Models, and Current Application in Human Clinical Trials

2020 ◽  
Vol 9 (4) ◽  
pp. 1102 ◽  
Author(s):  
Katarzyna Stefańska ◽  
Katarzyna Ożegowska ◽  
Greg Hutchings ◽  
Małgorzata Popis ◽  
Lisa Moncrieff ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Embryonic Stem ◽  
Wharton’S Jelly ◽  
Great Promise ◽  
Alternative Source ◽  
Current Application ◽  
Wharton's Jelly ◽  
Promising Source

Stem cell therapies offer a great promise for regenerative and reconstructive medicine, due to their self-renewal and differentiation capacity. Although embryonic stem cells are pluripotent, their utilization involves embryo destruction and is ethically controversial. Therefore, adult tissues that have emerged as an alternative source of stem cells and perinatal tissues, such as the umbilical cord, appear to be particularly attractive. Wharton’s jelly, a gelatinous connective tissue contained in the umbilical cord, is abundant in mesenchymal stem cells (MSCs) that express CD105, CD73, CD90, Oct-4, Sox-2, and Nanog among others, and have the ability to differentiate into osteogenic, adipogenic, chondrogenic, and other lineages. Moreover, Wharton’s jelly-derived MSCs (WJ-MSCs) do not express MHC-II and exhibit immunomodulatory properties, which makes them a good alternative for allogeneic and xenogeneic transplantations in cellular therapies. Therefore, umbilical cord, especially Wharton’s jelly, is a promising source of mesenchymal stem cells.

scholarly journals CHIP Reverses Hyperglycemia-associated PTEN Stability in Wharton's Jelly Derived Mesenchymal Stem Cells and Promotes Its Therapeutic Potential Against Diabetes-induced Cardiac Injury

2021 ◽  
Author(s):  
Ayaz Ali ◽  
Wei-Wen Kuo ◽  
Chia-Hua Kuo ◽  
Jeng-Feng Lo ◽  
Ray-Jade Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Injury ◽  
Wharton’S Jelly ◽  
Therapeutic Effects ◽  
Downstream Signaling ◽  
Wharton's Jelly ◽  
Induced Apoptosis ◽  
And Oxidative Stress

Abstract BackgroundRecent studies indicate that umbilical cord stem cells are cytoprotective against several disorders. One critical limitation in using stem cells is reduction in their viability under stressful conditions, such as diabetes. However, the molecular intricacies responsible for diabetic conditions are not fully elucidated.MethodsEffects of HG on Wharton's jelly derived mesenchymal stem cells (WJMSCs) viability was evaluated by MTT assay and flow cytometry. The mechanism responsible for HG-induced PTEN degradation was assessed using loss and gain of function, immunofluorescence, co-immunoprecipitation, and western blot analysis. Co-culturing of CHIP-overexpressed WJMSCs with embryo derived cardiomyoblasts was performed to analyze their ameliorative effects. The therapeutic effects of CHIP expressing WJMSCs were further validated in Sprague Dawley male (eight weeks old) STZ-induced diabetic animals by echocardiography, immunohistochemistry, hematoxylin eosin, and masson’s trichrome and TUNEL staining. Multiple comparisons were accessed through one‐way ANOVA and p-Value of <0.05 was considered statistically significant. ResultsIn this study, we found that high glucose (HG) conditions induced loss of chaperone homeostasis, stabilized PTEN, triggered the downstream signaling cascade, and induced apoptosis and oxidative stress in Wharton's jelly derived mesenchymal stem cells (WJMSCs). Increased CHIP expression promoted PTEN degradation via the ubiquitin-proteasome system and shortened its half-life during HG stress. Docking studies confirmed the interaction of CHIP with PTEN and FOXO3a with the Bim promoter region. Further, it was found that the chaperone system is involved in CHIP-mediated PTEN proteasomal degradation. CHIP depletion stabilizes PTEN whereas PTEN inhibition showed an inverse effect. CHIP overactivation suppressed the binding of FOXO3a with bim. Co-culturing CHIP overexpressed WJMSCs suppressed HG-induced apoptosis and oxidative stress in cardiac cells. Finally, CHIP overexpression and PTEN inhibition minimized blood glucose levels, improved body and heart weight, and rescued hyperglycemia-induced cardiac injury in diabetic rats. ConclusionThe current study suggests that CHIP confers resistance to apoptosis and oxidative stress and modulates PTEN and the downstream signaling cascade by promoting PTEN proteasomal degradation, thereby potentially exerting therapeutic effects against diabetes-induced cardiomyopathies.

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 Transplantation of Rat Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor 2α Improves Blood Perfusion and Arteriogenesis in a Rat Hindlimb Ischemia Model

2017 ◽  
Vol 2017 ◽  
pp. 1-11
Author(s):  
Weifeng Lu ◽  
Xiaoli Chen ◽  
Yi Si ◽  
Shichai Hong ◽  
Zhengyu Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Genetic Modification ◽  
Hypoxia Inducible Factor ◽  
Blood Perfusion ◽  
Tube Formation ◽  
Signaling Proteins ◽  
Hindlimb Ischemia ◽  
Cell Based Therapy ◽  
Therapeutic Benefits

Mesenchymal stem cells (MSCs) have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α) in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2α significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all P<0.05). rMSCHIF-2α transplantation also markedly increased the expression of proangiogenic factors VEGF, bFGF, and SDF1 and Notch signaling proteins including DII4, NICD, Hey1, and Hes1, whereas it reduced the expression of proapoptotic factor Bax in the muscle of the ischemic hindlimb. Overexpression of HIF-2α did not affect rMSC stemness and proliferation under normoxia but significantly increased rMSC migration and tube formation in matrigel under hypoxia (all P<0.05). RMSCsHIF-2α stimulated endothelial cell invasion under hypoxia significantly (P<0.05). Genetic modification of rMSCs via overexpression of HIF-2α improves posttransplantation outcomes in a rat hindlimb ischemia model possibly by stimulating proangiogenic growth factors and cytokines.

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