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Epigenetic Effects of Maternal Obesity on Wharton's Jelly (WJ) Mesenchymal Stromal Cells (MSCs): Implications For Cellular Therapy.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE107215 | GEO | 2017/11/21

SECONDARY ACCESSION(S): PRJNA419325

REPOSITORIES: GEO

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Epigenetic Effects of Maternal Obesity on Wharton's Jelly (WJ) Mesenchymal Stromal Cells (MSCs): Implications For Cellular Therapy. (expression study)

Project description:7 WJ-MSC lines from non-obese BMI <25 kg/m2 were compared with 7 WJ-MSC lines obese BMI >30 kg/m2. No template was used as a negative control Triplicates for each line were analyses for human whole-genome gene expression profile using HumanHT-12 v4.0 Expression BeadChip (Illumina).

2017-11-21 | GSE107214 | GEO

Epigenetic Effects of Maternal Obesity on Wharton's Jelly (WJ) Mesenchymal Stromal Cells (MSCs): Implications For Cellular Therapy. (methylation study)

Project description:7 WJ-MSC lines from non-obese BMI <25 kg/m2 were compared with 7 WJ-MSC lines obese BMI >30 kg/m2. No template was used as a negative control Triplicates for each line were analyses for epigenome-wide methylation (>480,000 CpG sites) using Infinium Human Methylation 450 BeadChip Kit (Illumina).

2016-10-16 | GSE74167 | GEO

Effects of maternal obesity on Wharton's Jelly mesenchymal stromal cells.

Project description:We investigated whether maternal metabolic environment affects mesenchymal stromal/stem cells (MSCs) from umbilical cord's Wharton's Jelly (WJ) on a molecular level, and potentially render them unsuitable for clinical use in multiple recipients. In this pilot study on umbilical cords post partum from healthy non-obese (BMI = 19-25; n = 7) and obese (BMI ≥ 30; n = 7) donors undergoing elective Cesarean section, we found that WJ MSC from obese donors showed slower population doubling and a stronger immunosuppressive activity. Genome-wide DNA methylation of triple positive (CD73+CD90+CD105+) WJ MSCs found 67 genes with at least one CpG site where the methylation difference was ≥0.2 in four or more obese donors. Only one gene, PNPLA7, demonstrated significant difference on methylome, transcriptome and protein level. Although the number of analysed donors is limited, our data suggest that the altered metabolic environment related to excessive body weight might bear consequences on the WJ MSCs.

| S-EPMC5730612 | biostudies-literature

Epigenetic Effects of Maternal Obesity on Wharton's Jelly (WJ) Mesenchymal Stromal Cells (MSCs): Implications For Cellular Therapy.

Project description:Epigenetic Effects of Maternal Obesity on Wharton's Jelly (WJ) Mesenchymal Stromal Cells (MSCs): Implications For Cellular Therapy.

| PRJNA419325 | ENA

Epigenetic Effects of Maternal Obesity on Wharton's Jelly (WJ) Mesenchymal Stromal Cells (MSCs): Implications For Cellular Therapy. (expression study)

Project description:Epigenetic Effects of Maternal Obesity on Wharton's Jelly (WJ) Mesenchymal Stromal Cells (MSCs): Implications For Cellular Therapy. (expression study)

| PRJNA419340 | ENA

An Injectable Hyaluronan-Methylcellulose (HAMC) Hydrogel Combined with Wharton's Jelly-Derived Mesenchymal Stromal Cells (WJ-MSCs) Promotes Degenerative Disc Repair.

Project description:Intervertebral disc (IVD) degeneration is one of the predominant causes of chronic low back pain (LBP), which is a leading cause of disability worldwide. Despite substantial progress in cell therapy for the treatment of IVD degeneration, significant challenges remain for clinical application. Here, we investigated the effectiveness of hyaluronan-methylcellulose (HAMC) hydrogels loaded with Wharton's Jelly-derived mesenchymal stromal cell (WJ-MSCs) in vitro and in a rat coccygeal IVD degeneration model. Following induction of injury-induced IVD degeneration, female Sprague-Dawley rats were randomized into four groups to undergo a single intradiscal injection of the following: (1) phosphate buffered saline (PBS) vehicle, (2) HAMC, (3) WJ-MSCs (2 × 104 cells), and (4) WJ-MSCs-loaded HAMC (WJ-MSCs/HAMC) (n = 10/each group). Coccygeal discs were removed following sacrifice 6 weeks after implantation for radiologic and histologic analysis. We confirmed previous findings that encapsulation in HAMC increases the viability of WJ-MSCs for disc repair. The HAMC gel maintained significant cell viability in vitro. In addition, combined implantation of WJ-MSCs and HAMC significantly promoted degenerative disc repair compared to WJ-MSCs alone, presumably by improving nucleus pulposus cells viability and decreasing extracellular matrix degradation. Our results suggest that WJ-MSCs-loaded HAMC promotes IVD repair more effectively than cell injection alone and supports the potential clinical use of HAMC for cell delivery to arrest IVD degeneration or to promote IVD regeneration.

| S-EPMC7582266 | biostudies-literature

Osteogenic commitment of Wharton's jelly mesenchymal stromal cells: mechanisms and implications for bioprocess development and clinical application.

Project description:BACKGROUND:Orthopaedic diseases are one of the major targets for regenerative medicine. In this context, Wharton's jelly (WJ) is an alternative source to bone marrow (BM) for allogeneic transplantation since its isolation does not require an invasive procedure for cell collection and does not raise major ethical concerns. However, the osteogenic capacity of human WJ-derived multipotent mesenchymal stromal cells (MSC) remains unclear. METHODS:Here, we compared the baseline osteogenic potential of MSC from WJ and BM cell sources by cytological staining, quantitative real-time PCR and proteomic analysis, and assessed chemical and biological strategies for priming undifferentiated WJ-MSC. Concretely, different inhibitors/activators of the TGFβ1-BMP2 signalling pathway as well as the secretome of differentiating BM-MSC were tested. RESULTS:Cytochemical staining as well as gene expression and proteomic analysis revealed that osteogenic commitment was poor in WJ-MSC. However, stimulation of the BMP2 pathway with BMP2 plus tanshinone IIA and the addition of extracellular vesicles or protein-enriched preparations from differentiating BM-MSC enhanced WJ-MSC osteogenesis. Furthermore, greater outcome was obtained with the use of conditioned media from differentiating BM-MSC. CONCLUSIONS:Altogether, our results point to the use of master banks of WJ-MSC as a valuable alternative to BM-MSC for orthopaedic conditions.

| S-EPMC6883559 | biostudies-literature

Concise Review: Wharton's Jelly: The Rich, but Enigmatic, Source of Mesenchymal Stromal Cells.

Project description:The umbilical cord has become an increasingly used source of mesenchymal stromal cells for preclinical and, more recently, clinical studies. Despite the increased activity, several aspects of this cell population have been under-appreciated. Key issues are that consensus on the anatomical structures within the cord is lacking, and potentially different populations are identified as arising from a single source. To help address these points, we propose a histologically based nomenclature for cord structures and provide an analysis of their developmental origins and composition. Methods of cell isolation from Wharton's jelly are discussed and the immunophenotypic and clonal characteristics of the cells are evaluated. The perivascular origin of the cells is also addressed. Finally, clinical trials with umbilical cord cells are briefly reviewed. Interpreting the outcomes of the many clinical studies that have been undertaken with mesenchymal stromal cells from different tissue sources has been challenging, for many reasons. It is, therefore, particularly important that as umbilical cord cells are increasingly deployed therapeutically, we strive to better understand the derivation and functional characteristics of the cells from this important tissue source. Stem Cells Translational Medicine 2017;6:1620-1630.

| S-EPMC5689772 | biostudies-literature

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

Project description: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.

| S-EPMC7547118 | biostudies-literature

Efficient Non-Viral Gene Modification of Mesenchymal Stromal Cells from Umbilical Cord Wharton's Jelly with Polyethylenimine.

Project description:Mesenchymal stromal cells (MSC) derived from human umbilical cord Wharton's jelly (WJ) have a wide therapeutic potential in cell therapy and tissue engineering because of their multipotential capacity, which can be reinforced through gene therapy in order to modulate specific responses. However, reported methodologies to transfect WJ-MSC using cationic polymers are scarce. Here, WJ-MSC were transfected using 25 kDa branched- polyethylenimine (PEI) and a DNA plasmid encoding GFP. PEI/plasmid complexes were characterized to establish the best transfection efficiencies with lowest toxicity. Expression of MSC-related cell surface markers was evaluated. Likewise, immunomodulatory activity and multipotential capacity of transfected WJ-MSC were assessed by CD2/CD3/CD28-activated peripheral blood mononuclear cells (PBMC) cocultures and osteogenic and adipogenic differentiation assays, respectively. An association between cell number, PEI and DNA content, and transfection efficiency was observed. The highest transfection efficiency (15.3 ± 8.6%) at the lowest toxicity was achieved using 2 ng/?L DNA and 3.6 ng/?L PEI with 45,000 WJ-MSC in a 24-well plate format (200 ?L). Under these conditions, there was no significant difference between the expression of MSC-identity markers, inhibitory effect on CD3+ T lymphocytes proliferation and osteogenic/adipogenic differentiation ability of transfected WJ-MSC, as compared with non-transfected cells. These results suggest that the functional properties of WJ-MSC were not altered after optimized transfection with PEI.

| S-EPMC7559368 | biostudies-literature

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