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: Adult stem cells are of particular importance for applications in regenerative medicine. Umbilical cord was established recently as an alternative source of mesenchymal stem cell (MSC) instead of bone marrow (BM) and is superior to BM and other adult tissues according to several MSC properties. Additionally, for the purpose of cell therapy in clinical scale, steps of cell isolation, expansion and culture required to be precisely adjusted in order to obtain the most cost-effective, least time-consuming, and least labor-intensive method. Therefore, in this study, we are going to compare two simple and cost-effective explant culture methods for isolation of MSCs from human umbilical cord. One of the methods isolates cells from entire cord and the other from Wharton's jelly matrix. Isolated cells then cultured in simple medium without addition of any growth factor. MSCs obtained via both methods display proper and similar characteristics according to morphology, population doubling time, post-thaw survival, surface antigenicity and differentiation into adipocytes, osteocytes, and chondrocytes. MSCs can easily be obtained from the entire cord and Wharton's jelly, and it seems that both tissues are appropriate sources of stem cells for potential use in regenerative medicine. However, from technical largescale preview, MSC isolation from entire cord piece is less labor-intensive and time-consuming than from Wharton's jelly part of the cord.Cell and Tissue Banking 02/2014; · 1.17 Impact Factor
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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: In addition to their differentiation potential, self-renewal capability is an important characteristic of stem cells. The limited self-renewal activity of mesenchymal stem cells is the greatest obstacle to the application of stem cell therapy in regenerative medicine. The human TERT gene enhances the self-renewal of MSCs, but the mechanism of self-renewal and the interactions among TERT-gene-related molecules remain unknown. The objectives of this study were to generate immortalized MSCs derived from MSCs isolated from placenta (naive) by human TERT gene transfection with the AMAXA gene delivery system, to compare their characteristics, and to investigate whether increased TERT expression affected the pituitary tumor transforming gene (PTTG1; also known as securin), which is involved in chromosome segregation during mitosis. TERT-immortalized cells (TERT+) with a prolonged life span displayed high PTTG1 expression. TERT+ cells also retained the stemness capacity and multipotency of naive cells and displayed high PTTG1 expression. However, down-regulation of PTTG1 by treatment with short interfering RNA induced cell senescence and decreased telomerase activity. Moreover, TERT bound to PTTG1 formed complexes with chaperones such as Ku70 and heat shock protein 90. Thus, placental MSCs immortalized by TERT gene transfection display differentiation potential and exhibit enhanced self-renewal through a balanced interaction of PTTG1 and chaperones. The interaction between TERT and PTTG1 by association of Ku70 might be important for the enhancement of the limited self-renewal activity of MSCs and for understanding the regulatory mechanisms of self-renewal.Cell and Tissue Research 05/2014; · 3.68 Impact Factor