Proliferation Potential Of Mesenchymal Stem Cells Research Articles

Optimizing Mesenchymal Stem Cells for Regenerative Medicine: Influence of Diabetes, Obesity, Autoimmune, and Inflammatory Conditions on Therapeutic Efficacy: A Review.

Mesenchymal stem cells (MSCs) are a promising tool that may be used in regenerative medicine. Thanks to their ability to differentiate and paracrine signaling, they can be used in the treatment of many diseases. Undifferentiated MSCs can support the regeneration of surrounding tissues through secreted substances and exosomes. This is possible thanks to the production of growth factors. These factors stimulate the growth of neighboring cells, have an anti-apoptotic effect, and support angiogenesis, and MSCs also have an immunomodulatory effect. The level of secreted factors may vary depending on many factors. Apart from the donor's health condition, it is also influenced by the source of MSCs, methods of harvesting, and even the banking of cells. This work is a review of research on how the patient's health condition affects the properties of obtained MSCs. The review discusses the impact of the patient's diabetes, obesity, autoimmune diseases, and inflammation, as well as the impact of the source of MSCs and methods of harvesting and banking cells on the phenotype, differentiation capacity, anti-inflammatory, angiogenic effects, and proliferation potential of MSCs. Knowledge about specific clinical factors allows for better use of the potential of stem cells and more appropriate targeting of procedures for collecting, multiplying, and banking these cells, as well as for their subsequent use. This article aims to review the characteristics, harvesting, banking, and paracrine signaling of MSCs and their role in diabetes, obesity, autoimmune and inflammatory diseases, and potential role in regenerative medicine.

Effects of therapeutic doses of heparin on MSC functional activity in modeling the mechanisms of osteointegration under in vitro cultivation

The use of artificial materials in regenerative medicine is accompanied by the development of an inflammatory response and the initiation of blood clotting due to the contact of the implant with the soft tissues of the body. All this leads to the formation of thrombosis of the major and main arteries and the development of serious complications. To prevent the development of postoperative pathological conditions caused by hypercoagulable syndrome, classical therapeutic strategies with anticoagulants (mainly heparin) are used. However, the described treatment tactics lead to an interruption of the migration and adhesion processes of mesenchymal stem cells (MSC), which negatively affects the callus formation and the processes of osseointegration of the implant. The aim of this study was to investigate the effect of a suspension of HA nanoparticles in the presence of heparin in a gradient of therapeutic concentrations on migratory and proliferative activity of MSCs in human adipose tissue under in vitro cultivation conditions. Methods. To evaluate the migration and proliferation potential of MSC in the presence of HA nanosuspension and/or heparin, an electrode system for continuous observation — xCELLigence ® RTCA DP was used. Results. A significant decrease in the migratory activity and proliferative potential of MSC was observed under the conditions of their co-cultivation with HA nanosuspension in the presence/absence of heparin (0.5–1 IU/ml). onclusion. The results of the study may serve as a prerequisite for the development of new therapeutic approaches for the use of heparin in surgical patients at high risk of postoperative thrombosis after osteosynthesis.

Correlation of TCF4, GSK, TERT and TERC Expressions with Proliferation Potential of Early and Late Culture of Human Peripheral Blood Mesenchymal Stem Cells.

Objective In the recent years, mesenchymal stem cells (MSCs) were considered as the suitable source of cells for transplantation into the damaged tissues in regenerative medicine. There was low number of these cells in different organs and this characteristic was the main drawback to use them in treatment of diseases. Cellular senescence of the stem cells has been demonstrated to be dependent to the telomerase activity. The aim of present experimental study was to evaluate correlation of the expression of telomerase components and WNT signaling pathway in MSCs derived from human peripheral blood (PB-MSCs). Materials and Methods In this experimental study, following the isolation of MSCs from peripheral blood mononuclear cells, RNA was extracted from these cells in the early culture (8-9th days) and late culture (14-17th days). Then, expression of TERT, TERC, TCF4, GSK and CTNNB1 was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) based on SYBR Green. Results Our data indicated that there was a significantly reduced expression of TERT in the late culture of human MSCs derived from peripheral blood (P<0.05). Although a negative correlation was observed between GSK and TERC expression levels in the early culture of MSCs, spearman analysis showed that there was no significant correlation between the expression of telomerase components (TERC and TERT) and WNT signaling pathway (P>0.05). ConclusionThe obtained results suggested that WNT signaling pathway likely plays a minor role in the maintenance of telomere length and proliferation potential of MSCs.

Mesenchymal stem cells and JIA

Background Mesenchymal stem cells (MSC) are adult stem cells present in bone marrow (BM), fat and in many other tissues. MSC have strong immunosuppressive qualities in vitro. The immunosuppression seems to work both by paracrine action and cell-cell contact. MSC inhibit NKcells, B-cells, dendritic cells, Th1-cells and activate regulatory T-cells. The presence of floating single MSC in human synovial fluid (SF) is a normal phenomenon and the number of MSC in SF is much lower in RA than in osteoarthritis (OA). SF in RA might be impaired in recruiting MSC to the joint and the proliferation potential of MSC in RA patients could be suppressed by the synovitis or be exhausted as suggested by the decreased telomere length. Administration of additional MSC might therefore have great potential in the treatment of inflammatory arthritis as we and others have shown in different experimental arthritis models.

Clonal analysis of the proliferation potential of human bone marrow mesenchymal stem cells as a function of potency

Human mesenchymal stem cells (MSCs) from bone marrow are a heterogeneous ensemble of progenitors and lineage-committed cells, with a broad range of regenerative properties. Ex vivo expansion to produce sufficient quantities of MSCs is essential for most therapeutic applications. The present study resolves the relationship between proliferation potential of MSCs and their potency. Clonal analysis generated single-cell derived colonies of MSCs that were classified according to their trilineage potential to exhibit adipo- (A), chondro- (C), and osteogenesis (O) as a measure of potency. Multipotent OAC clones were highly proliferative with colony-forming efficiencies that ranged from 35% to 90%; whereas, O clones formed colonies with an efficiency of 5% or less (P < 0.01). Similar trends were evident during ex vivo expansion: for example, the median specific growth rate was 0.8 day(-1) (20 h doubling time) for cultures inoculated with OAC clones and was 5-fold less for inocula of O clones (P < 0.01). OA and OC clones had similar proliferation potentials. More than 75% of cells in subconfluent cultures inoculated with O clones stained positive for senescence-associated β-galactosidase activity vs. less than 10% for OAC clones (P < 0.001). Apoptotic cells were in the minority for all potency groups. Preliminary data generated during clonal analysis suggest that osteogenic potential of MSCs to produce mineralized matrix is a function of potency, as well. These results are discussed in the context of the preparation of efficacious MSC therapies by ex vivo expansion.

Histocompatibility testing of cultivated human bone marrow stromal cells – A promising step towards pre-clinical screening for allogeneic stem cell therapy

Mesenchymal stem cells (MSCs) lack major histocompatibility complex (MHC)-II and only show minimal MHC-I expression. Despite MSCs demonstrating T-cell anergy, there are no established methods to evaluate their suitability. It is crucial to evaluate the complete mismatch of MHC compatibility in view of the hypo-immunogenic nature and immunomodulatory properties of MSCs with respect to their proliferation potential (PP) and utility in terms of passage number. With bone marrow (BM) being the major source of MSCs, the use of these cells becomes even more complicated, due to many other receptors coming to fore and triggering alternative pathways. This prospective study included five BM aspirates for MSC cultures and five allogeneic peripheral blood mono nuclear cells (PBMNCs) from healthy volunteers. MHC compatibility was assessed by polymerase chain reaction-sequence specific primer (PCR-SSP). The PP and a T-cell response to MSCs was addressed in mixed cultures and evaluated on the basis of their stimulation index (SI). Allogeneic circulatory antibodies against the donor MSCs was performed by cytotoxicity assay. The PP of MSCs during interactions with PBMNCs (T-cells) demonstrated T-cell anergy and the response to circulatory antibodies was minimal, in consonance with other published reports. Although, the results are encouraging for potential clinical application of MSC transplantation, autologous is always preferable to allogeneic, at least until the long-term safety of these cells is established in clinical trials.