Human chorionic-plate-derived mesenchymal stem cells and Wharton's jelly-derived mesenchymal stem cells: a comparative analysis of their potential as placenta-derived stem cells.
ABSTRACT Placenta-derived stem cells (PDSCs) have gained interest as an alternative source of stem cells for regenerative medicine because of their potential for self-renewal and differentiation and their immunomodulatory properties. Although many studies have characterized various PDSCs biologically, the properties of the self-renewal and differentiation potential among PDSCs have not yet been directly compared. We consider the characterization of chorionic-plate-derived mesenchymal stem cells (CP-MSCs) and Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) among various PDSCs and the assessment of their differentiation potential to be important for future studies into the applicability and effectiveness of PDSCs in cell therapy. In the present study, the capacities for self-renewal and multipotent differentiation of CP-MSCs and WJ-MSC isolated from normal term placentas were compared. CP-MSCs and WJ-MSCs expressed mRNAs for the pluripotent stem cell markers Oct-4, Nanog, and Sox-2. Additionally, HLA-G for immunomodulatory effects was found to be expressed at both the mRNA and protein levels in both cell types. The CP-MSCs and WJ-MSCs also had the capacities to differentiate into cells of mesodermal (adipogenic and osteogenic) and endodermal (hepatogenic) lineages. Expression of adipogenesis-related genes was higher in CP-MSCs than in WJ-MSCs, whereas WJ-MSCs accumulated more mineralized matrix than CP-MSCs. The WJ-MSCs expressed more of CYP3A4 mRNA, a marker for mature hepatocytes, than CP-MSCs. Thus, we propose that CP-MSCs and WJ-MSCs are useful sources of cells for appropriate clinical applications in the treatment of various degenerative diseases.
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ABSTRACT: Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) have shown a good safety profile and therapeutic effect in severe and refractory systemic lupus erythematosus (SLE) in our single-center pilot study. The present multicenter clinical trial was undertaken to assess the safety and efficacy of allogenic UC MSC transplantation (MSCT) in active and refractory SLE patients. Forty patients with active SLE were enrolled from 4 clinical centers in China. Allogenic UC MSCs were infused intravenously on days 0 and 7. Primary endpoints were safety profiles. Second endpoints included major clinical response (MCR), partial clinical response (PCR) and relapse. Clinical index including SLEDAI score, BILAG score, renal functional indices were also determined. The overall survival rate was 92.5% (37/40). UC-MSCT was well tolerated, and no transplantation-related adverse event was observed. Thirteen and eleven patients achieved MCR (13/40, 32.5%) and PCR (11/40, 27.5%) during 12 months follow-up, respectively. Then three and four patients experienced disease relapse at 9 (12.5%) and 12 (16.7%) months follow-up, after a prior clinical response. SLEDAI score significantly decreased at 3, 6, 9 and 12 months follow-up. Total BILAG score markedly decreased at 3 months and continued to decrease at subsequent follow-up visits. BILAG scores for renal, hematopoietic and cutaneous systems significantly improved. For those with lupus nephritis, 24-hour proteinuria declined after transplantation, with statistical differences at 9 and 12 months. Serum creatinine and urea nitrogen decreased to the lowest level at 6 months, while these values slightly increased at 9 and 12 months as a result of 7 relapsed cases. In addition, serum levels of albumin and complement 3 increased after MSCT, peaked at 6 months and then slightly declined at 9 and 12 months follow-up. Serum antinuclear antibody and anti-double-strand DNA antibody decreased after MSCT, with statistical differences at 3 months follow-up. UC-MSCT results in satisfactory clinical response in SLE patients. However, several cases experienced disease relapse after 6 months, indicating the necessity to repeat MSCT after 6 months.Registration number: NCT01741857.Arthritis research & therapy 03/2014; 16(2):R79. · 4.27 Impact Factor
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ABSTRACT: Keloid scars are abnormal benign fibroproliferative tumors with high recurrence rates and no current efficacious treatment. Accumulating evidence suggests that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have antifibrotic properties. Paracrine signaling is considered one of the main underlying mechanisms behind the therapeutic effects of mesenchymal stem cells. However, the paracrine signaling effects of WJ-MSCs on keloids have not yet been reported. The aim of this study is to investigate paracrine signaling effects of human WJ-MSCs on keloid fibroblasts in vitro. Human umbilical cords and keloid skin samples were obtained, and WJ-MSCs and keloid fibroblasts were isolated and cultured. One-way and two-way paracrine culture systems between both cell types were investigated. Plasminogen activator inhibitor-I and transforming growth factor-β2 (TGF-β2) transcripts were upregulated in keloid fibroblasts cultured with WJ-MSC-conditioned medium (WJ-MSC-CM) and cocultured with inserts, while showing lower TGF-β3 gene expression. Interleukin (IL)-6, IL-8, TGF-β1, and TGF-β2 protein expression was also enhanced. The WJ-MSC-CM-treated keloid fibroblasts showed higher proliferation rates than their control keloid fibroblasts with no significant change in apoptosis rate or migration ability. In our culture conditions, the indirect application of WJ-MSCs on keloid fibroblasts may enhance their profibrotic phenotype.STEM CELLS TRANSLATIONAL MEDICINE 01/2014; · 3.60 Impact Factor
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ABSTRACT: Mesenchymal stem cells (MSCs) have a capacity for self-renewal and multi-potential differentiations. These cells are considered powerful sources for cell therapy in regenerative medicine and tissue engineering. The cells can be isolated from various tissues; however, harvesting from human umbilical cord and amniotic membrane is easy and accessible source.International journal of organ transplantation medicine. 01/2013; 4(3):111-6.