scholarly journals Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity

2020 ◽  
Vol 9 (9) ◽  
pp. 2913
Author(s):  
Ji Yeon Kang ◽  
Mi-Kyung Oh ◽  
Hansol Joo ◽  
Hyun Sung Park ◽  
Dong-Hoon Chae ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Experimental Colitis ◽  
Wharton’S Jelly ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Wharton's Jelly ◽  
Indoleamine 2,3 Dioxygenase ◽  
Immunomodulatory Properties ◽  
Anti Inflammatory

The therapeutic applications of mesenchymal stem cells (MSCs) have been actively explored due to their broad anti-inflammatory and immunomodulatory properties. However, the use of xenogeneic components, including fetal bovine serum (FBS), in the expansion media might pose a risk of xenoimmunization and zoonotic transmission to post-transplanted patients. Here, we extensively compared the physiological functions of human Wharton’s jelly-derived MSCs (WJ-MSCs) in a xeno-free medium (XF-MSCs) and a medium containing 10% FBS (10%-MSCs). Both groups showed similar proliferation potential; however, the 10%-MSCs showed prolonged expression of CD146, with higher colony-forming unit-fibroblast (CFU-F) ability than the XF-MSCs. The XF-MSCs showed enhanced adipogenic differentiation potential and sufficient hematopoietic stem cell (HSC) niche activity, with elevated niche-related markers including CXCL12. Furthermore, we demonstrated that the XF-MSCs had a significantly higher suppressive effect on human peripheral blood-derived T cell proliferation, Th1 and Th17 differentiation, as well as naïve macrophage polarization toward an M1 phenotype. Among the anti-inflammatory molecules, the production of indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase 2 (NOS2) was profoundly increased, whereas cyclooxygenase-2 (COX-2) was decreased in the XF-MSCs. Finally, the XF-MSCs had an enhanced therapeutic effect against mouse experimental colitis. These findings indicate that xeno-free culture conditions improved the immunomodulatory properties of WJ-MSCs and ex vivo-expanded XF-MSCs might be an effective strategy for preventing the progression of colitis.

scholarly journals Different Angiogenic Potentials of Mesenchymal Stem Cells Derived from Umbilical Artery, Umbilical Vein, and Wharton’s Jelly

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Lu Xu ◽  
Jianjun Zhou ◽  
Jingyu Liu ◽  
Yong Liu ◽  
Lei Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Vein ◽  
Wharton’S Jelly ◽  
Tube Length ◽  
Branch Points ◽  
Differentiation Potential ◽  
Wharton's Jelly ◽  
Allogeneic Cell Therapy ◽  
Perivascular Stem Cells

Human mesenchymal stem cells derived from the umbilical cord (UC) are a favorable source for allogeneic cell therapy. Here, we successfully isolated the stem cells derived from three different compartments of the human UC, including perivascular stem cells derived from umbilical arteries (UCA-PSCs), perivascular stem cells derived from umbilical vein (UCV-PSCs), and mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs). These cells had the similar phenotype and differentiation potential toward adipocytes, osteoblasts, and neuron-like cells. However, UCA-PSCs and UCV-PSCs had more CD146+ cells than WJ-MSCs (P<0.05). Tube formation assay in vitro showed the largest number of tube-like structures and branch points in UCA-PSCs among the three stem cells. Additionally, the total tube length in UCA-PSCs and UCV-PSCs was significantly longer than in WJ-MSCs (P<0.01). Microarray, qRT-PCR, and Western blot analysis showed that UCA-PSCs had the highest expression of the Notch ligand Jagged1 (JAG1), which is crucial for blood vessel maturation. Knockdown of Jagged1 significantly impaired the angiogenesis in UCA-PSCs. In summary, UCA-PSCs are promising cell populations for clinical use in ischemic diseases.

scholarly journals Wharton’s jelly-derived mesenchymal stem cells attenuate sepsis-induced organ injury partially via cholinergic anti-inflammatory pathway activation

2020 ◽  
Vol 318 (1) ◽  
pp. R135-R147 ◽  
Author(s):  
José Manuel Cóndor Capcha ◽  
Camila Eleutério Rodrigues ◽  
Roberto de Souza Moreira ◽  
Marcelo Duarte Silveira ◽  
Paulo Dourado ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Systemic Inflammation ◽  
Cecal Ligation ◽  
Wharton’S Jelly ◽  
Organ Injury ◽  
Experimental Sepsis ◽  
Inflammatory Pathway ◽  
Wharton's Jelly ◽  
Anti Inflammatory

Sepsis induces organ dysfunction due to overexpression of the inflammatory host response, resulting in cardiopulmonary and autonomic dysfunction, thus increasing the associated morbidity and mortality. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) express genes and secrete factors with anti-inflammatory properties, neurological and immunological protection, as well as improve survival in experimental sepsis. The cholinergic anti-inflammatory pathway (CAP) is mediated by α7-nicotinic acetylcholine receptors (α7nAChRs), which play an important role in the control of systemic inflammation. We hypothesized that WJ-MSCs attenuate sepsis-induced organ injury in the presence of an activated CAP pathway. To confirm our hypothesis, we evaluated the effects of WJ-MSCs as a treatment for cardiopulmonary injury and on neuroimmunomodulation. Male Wistar rats were randomly divided into four groups: control (sham-operated); cecal ligation and puncture (CLP) alone; CLP+WJ-MSCs (1 × 106 cells, at 6 h post-CLP); and CLP+methyllycaconitine (MLA)+WJ-MSCs (5 mg/kg body wt, at 5.5 h post-CLP, and 1 × 106 cells, at 6 h post-CLP, respectively). All experiments, including the assessment of echocardiographic parameters and heart rate variability, were performed 24 h after CLP. WJ-MSC treatment attenuated diastolic dysfunction and restored baroreflex sensitivity. WJ-MSCs also increased cardiac sympathetic and cardiovagal activity. WJ-MSCs reduced leukocyte infiltration and proinflammatory cytokines, effects that were abolished by administration of a selective α7nAChR antagonist (MLA). In addition, WJ-MSC treatment also diminished apoptosis in the lungs and spleen. In cardiac and splenic tissue, WJ-MSCs downregulated α7nAChR expression, as well as reduced the phospho-STAT3-to-total STAT3 ratio in the spleen. WJ-MSCs appear to protect against sepsis-induced organ injury by reducing systemic inflammation, at least in part, via a mechanism that is dependent on an activated CAP.

Investigation of immunomodulatory properties of Human Wharton’s Jelly-derived Mesenchymal Stem Cells after lentiviral transduction

2015 ◽  
Vol 293 (2) ◽  
pp. 59-66 ◽  
Author(s):  
Afshin Amari ◽  
Massoumeh Ebtekar ◽  
Seyed Mohammad Moazzeni ◽  
Masoud Soleimani ◽  
Leila Mohammadi Amirabad ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wharton’S Jelly ◽  
Lentiviral Transduction ◽  
Wharton's Jelly ◽  
Immunomodulatory Properties

Differentiation potential of different regions-derived same donor human Wharton’s jelly mesenchymal stem cells into functional smooth muscle-like cells

2019 ◽  
Vol 377 (2) ◽  
pp. 229-243
Author(s):  
Dinesh Bharti ◽  
Sharath Belame Shivakumar ◽  
Young-Bum Son ◽  
Young-Ho Choi ◽  
Imran Ullah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Wharton’S Jelly ◽  
Differentiation Potential ◽  
Wharton's Jelly

scholarly journals Effects of MRI on Stemness Properties of Wharton’s Jelly Derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Mahnaz Tashakori ◽  
Fatemeh Asadi ◽  
Faezeh-Sadat Khorram ◽  
Azita Manshoori ◽  
Ali Hosseini-Chegeni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Doubling Time ◽  
Expression Patterns ◽  
Wharton’S Jelly ◽  
Population Doubling ◽  
Control Group ◽  
Differentiation Potential ◽  
Wharton's Jelly ◽  
Promising Source

Abstract BackgroundMesenchymal stem cells (MSCs), derived from various tissues, have served as a promising source of cells in clinic and regenerative medicine. Umbilical cord-Wharton’s jelly (WJ-MSCs)-derived MSCs exhibit advantages over those from adult tissues, such as no ethical concerns, shorter population doubling time, broad differentiation potential, readily available non-invasive source, prolonged maintenance of stemness properties. Material and methodsThe aim of this study was to evaluate the effect of MRI (1.5 T, 10 min) on stemness gene expression patterns (OCT-4, SOX-2, NANOG) of WJ-MSCs. In addition, we assessed cell viability, growth kinetics and apoptosis of WJ-MSCs after MRI treatment. ResultsThe quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) data showed that transcript levels of SOX-2, NANOG in MRI-treated WJ-MSCs were increased 32- and 213-fold, respectively. MTT assay was performed at 24, 48, and 72 hours post-treatment and the viability was not significantly difference between two groups. The doubling time of MRI group was markedly higher than control group. In addition, the colony formation ability of WJ-MSCs after MRI treatment significantly increased. Furthermore, no change in apoptosis was seen before or after MRI treatment. ConclusionsOur results suggest the use of MRI can improve quality of MSCs and may enhance the efficacy of mesenchymal stem cell-based therapies.

Effect of Human Platelet Lysate in Differentiation of Wharton’s Jelly Derived Mesenchymal Stem Cells

2019 ◽  
Vol 19 (8) ◽  
pp. 1177-1191 ◽  
Author(s):  
Rosy Vennila ◽  
Raja Sundari M. Sundaram ◽  
Sakthivel Selvaraj ◽  
Prasanna Srinivasan ◽  
Surajit Pathak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Platelet Lysate ◽  
Wharton’S Jelly ◽  
Differentiation Potential ◽  
Animal Products ◽  
Clinical Therapy ◽  
Wharton's Jelly ◽  
Human Platelet Lysate ◽  
Brdu Assay

Background: Mesenchymal stem cells (MSCs) are highly preferred in clinical therapy for repair and regeneration of diseased tissues for their multipotent properties. Conventionally, MSCs have been cultured in media supplemented with animal derived serum, however, it is ideal to expand MSCs in media containing supplements of human origin for clinical therapy. Currently, a number of human derived products are being studied as an alternative to animal sources. Amongst these, platelet lysate (PL) has gained interest in the culture of MSCs without affecting their phenotypic property. Objective: In this study, we used various concentration of PL (2.5, 5, 7.5 & 10%) in the growth medium of MSCs to identify the least concentration of PL that could be an effective alternative to animal products. Methods: MSCs were isolated from Wharton’s Jelly by using explant method and expanded in various concentration of PL supplemented medium against the standard FBS containing medium. WJ-MSCs were characterised as per the minimal criteria proposed by International Society for Cell therapy (ISCT), Proliferation study by BrdU assay, gene expression study by qRT-PCR, sterility test for bacteria, Mycoplasma by PCR and endotoxin detection by LAL assay. Results: Whartons jelly derived MSCs (WJ-MSCs) cultured using standard medium supplemented with various concentration of PL exhibited enhanced proliferation and differentiation potential, unaltered immunophenotypic property and genetic stability when compared with the commercial medium containing 10% FBS. Conclusion: The least concentration of PL for an ideal expansion of MSCs was found to be 2.5% and was comparable to FBS.

scholarly journals Comparative Proteomic Analysis Identifies EphA2 as a Specific Cell Surface Marker for Wharton’s Jelly-Derived Mesenchymal Stem Cells

2020 ◽  
Vol 21 (17) ◽  
pp. 6437
Author(s):  
Ashraf Al Madhoun ◽  
Sulaiman K. Marafie ◽  
Dania Haddad ◽  
Motasem Melhem ◽  
Mohamed Abu-Farha ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transmembrane Domain ◽  
Expression Patterns ◽  
Wharton’S Jelly ◽  
Mass Spectrometry Analysis ◽  
Specific Cell ◽  
Specific Marker ◽  
Differentiation Potential ◽  
Wharton's Jelly

Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are a valuable tool in stem cell research due to their high proliferation rate, multi-lineage differentiation potential, and immunotolerance properties. However, fibroblast impurity during WJ-MSCs isolation is unavoidable because of morphological similarities and shared surface markers. Here, a proteomic approach was employed to identify specific proteins differentially expressed by WJ-MSCs in comparison to those by neonatal foreskin and adult skin fibroblasts (NFFs and ASFs, respectively). Mass spectrometry analysis identified 454 proteins with a transmembrane domain. These proteins were then compared across the different cell-lines and categorized based on their cellular localizations, biological processes, and molecular functions. The expression patterns of a selected set of proteins were further confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence assays. As anticipated, most of the studied proteins had common expression patterns. However, EphA2, SLC25A4, and SOD2 were predominantly expressed by WJ-MSCs, while CDH2 and Talin2 were specific to NFFs and ASFs, respectively. Here, EphA2 was established as a potential surface-specific marker to distinguish WJ-MSCs from fibroblasts and for prospective use to prepare pure primary cultures of WJ-MSCs. Additionally, CDH2 could be used for a negative-selection isolation/depletion method to remove neonatal fibroblasts contaminating preparations of WJ-MSCs.

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