Mesenchymal stem cells (MSC) have received much attention in the field of hematopoietic stem cell transplantation because not only do they support hematopoiesis but also exhibit a profound immunosuppressive activity that can be exploited to prevent undesired alloreactivity. We have previously shown that their immunosuppressive activity is mainly exerted at the level of T-cell proliferation. Here, we show that MSC exhibit a similar antiproliferative activity on tumor cells of hematopoietic and non hematopoietic origin. In vitro, MSC produced the transient arrest of tumor cells in the G 1 phase of cell cycle; this was accompanied by a reduction in the apoptotic rate even when survival factors were limiting. However, when tumor cells were injected into non-obese diabetic-severe combined immunodeficient mice in conjunction with MSC, their growth was much faster as compared to the group receiving only tumor cells. To explain the discrepancy between the in vitro and in vivo behavior, we suggest that MSC have the ability to form a cancer stem cell niche in which tumor cells can preserve the potential to proliferate and sustain the malignant process. We conclude that the clinical use of MSC in conditions in which a malignant disease is involved should be handled with extreme caution.
We conclude that MSCs impair monocyte differentiation and function by interfering with the cell cycle. These findings imply that MSC-induced immunosuppression might be a side product of a more general antiproliferative effect.
Material
binding peptides are proving to have great potential in
improving material synthesis and advancing device fabrication; however,
their specificity and interaction mechanisms with target surfaces
remain largely elusive. This study contributes to the developing understanding
of fundamental principles through which ZnO binding peptides (ZnO-BPs)
interact with and modify ZnO growth/morphology. The ZnO-BPs used were
the reported phage display (PD) identified sequence (G-12 (GLHVMHKVAPPR)
and its derivative, GT-16 (GLHVMHKVAPPR-GGGC)) as well as novel sequences
generated from postselection modifications including alanine mutants
of G-12 (G-12A6, G-12A11, and G-12A12) chosen on the basis of peptide
stability calculated in silico. ZnO growth was monitored
in the absence and presence of ZnO-BPs during solution synthesis using
two different growth routes: the Zn(NO3)2·6H2O–HMTA system and the Zn(CH3COO)2–NH3 system. The outcomes of the ZnO synthesis
studies demonstrate that a single ZnO-BP can utilize different sequence
and concentration dependent mechanisms to control ZnO growth and generate
different morphologies. The specific synthesis system used dictated
the species present in solution and the solid phases formed, some
of which ZnO-BPs could interact with and consequently modify ZnO growth
and resultant morphologies. The role of histidine within ZnO-BPs in
interaction with ZnO and stabilization of LBZs is also demonstrated.
MSCs (mesenchymal stem cells) promise a great potential for regenerative medicine due to their unique properties of self-renewal, high plasticity, modulation of immune response and the flexibility for genetic modification. Therefore, the increasing demand for cellular therapy necessitates a larger-scale production of MSC; however, the technical and ethical issues had put a halt on it. To date, studies have shown that MSC could be derived from human UC (umbilical cord), which is once considered as clinical waste. We have compared the two conventional methods which are classic enzymatic digestion and explant method with our newly tailored enzymatic-mechanical disassociation method to generate UC-MSC. The generated UC-MSCs from the methods above were characterized based on their immunophenotyping, early embryonic transcription factors expression and mesodermal differentiation ability. Our results show that enzymatic-mechanical disassociation method increase the initial nucleated cell yield greatly (approximately 160-fold) and maximized the successful rate of UC-MSC generation. Enzymatic-mechanical disassociation-derived UC-MSC exhibited fibroblastic morphology and surface markers expression of CD105, CD73, CD29, CD90 and MHC class I. Furthermore, these cells constitutively express early embryonic transcription factors (Nanog, Oct-4, Sox-2 and Rex-1), as confirmed by RT-PCR, indicating their multipotency and high self-renewal capacity. They are also capable of differentiating into osteoblasts and adipocytes when given an appropriate induction. The present study demonstrates a new and efficient approach in generating MSC from UC, hence serving as ideal alternative source of mesenchymal stem cell for clinical and research use.
AIM:To explore the feasibility of placenta tissue as a reliable and efficient source for generating mesenchymal stem cells (MSC).
METHODS:MSC were generated from human placenta tissue by enzymatic digestion and mechanical dissociation. The placenta MSC (PLC-MSC) were characterized for expression of cell surface markers, embryonic stem cell (ECS) gene expression and their differentiation ability into adipocytes and osteocytes. The immunosuppressive properties of PLC-MSC on resting and phytohemagglutinin (PHA) stimulated allogenic T cells were assessed by means of cell proliferation via incorporation of tritium thymidine ( 3 H-TdR).
RESULTS:The generated PLC-MSC appeared as spindle-shaped cells, expressed common MSC surface markers and ESC transcriptional factors. They also differentiated into adipogenic and osteogenic lineages when induced. However, continuous cultivation up to passage 15 caused changes in morphological appearance and cellular senescence, although the stem cell nature of their protein expression was unchanged. In terms of their immunosuppressive properties, PLC-MSC were unable to stimulate resting T cell proliferation; they inhibited the PHA stimulated T cells in a dose dependent manner through cell to cell contact. In our study, MSC generated from human placenta exhibited similar mesenchymal cell surface markers; MSC-like gene expression pattern and MSC-like differentiation potential were comparable to other sources of MSC.
CONCLUSION:We suggest that placenta tissues can serve as an alternative source of MSC for future experimental and clinical studies.
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