Immunomodulation is essential for controlling the immune system to maintain efficient immune surveillance and inflammation. Both arms of immunomodulation, namely immunostimulation and immunosuppression, are equally crucial in setting the optimal balance of immune response. However, diseases or conditions such as autoimmune diseases, tissue rejection due to transplantation and chronic inflammation require downregulation of overwhelming immune reactions. The conventional immunosuppressive drugs prevent the activation of immune cells, yet create an unsafe condition with toxic adverse effects. In such predicament, mesenchymal stem cells (MSCs) emerged as one of the safe immunosuppressive regiments and widely tested in clinical trials for numerous chronic inflammatory dis-eases. Mesenchymal stem cells are the origin of the stromal/mesenchymal cells in almost all solid organs, including the pulp of the tooth. In addition to providing structural support to the organ, MSCs participate in the tissue repair and regeneration by ameliorating an overly activated immune response locally and systemically. Regardless of the source, MSCs profoundly suppress the proliferation and effector functions of both innate and adaptive immune cells. The mechanism of inhibition primarily took place in the early phase of cell cycle and mediated via suppression of mainstream signalling pathways that involve cyclins and other cell cycle proteins. The antiproliferative activity of MSCs is not only limited to the healthy immune cells but extends to the various tumour cells of the immune system. Similarly, an array of cell signalling pathways that executed by cell cycle proteins found downregulated in the pres-ence of MSCs. The immunosuppressive activity exerted by MSCs is not specific to particular immune cells where it impairs a group of the common cell signalling pathways or putative cell cycle proteins which are vital elements for the proliferation.
Human cartilage contains multipotent stem cells, namely mesenchymal stem cells (MSCs) which are progenitors of connective tissue that play homeostatic and reparative roles. Although the major constituent cells in the cartilage are chondrocytes, they possess a limited regenerative ability, and as a result, spontaneous cartilage repair by chondro- cytes leads to the synthesis of fibrocartilage. Similarly, MSCs derived from articular cartilage of osteoarthritis patients have demonstrated inadequacy in cartilage repair. The role of MSCs in the pathophysiology of osteoarthritis (OA) is not entirely understood, whether the inflammatory milieu associated with OA joints affects the reparative properties of MSCs or the inherent defects of OA cartilage-derived MSCs impair the proper execution of the required immu- nosuppressive and reparative functions. Therefore, the current review explores the biological characteristics and features of MSCs derived from physiological state and OA condition with the aim of identifying how OA affects MSC functions as well as the role of MSCs in the pathophysiology of OA.
Introduction: Monocytes are essential phagocytic cells of the innate immune system as they are required for
the maintenance of tissue homeostasis. However, accumulation of monocytes is implicated in various chronic
inflammatory diseases like coronary heart disease, atherosclerosis and in autoimmune disorders. Therefore, the
number of monocytes must be carefully regulated to avoid monocyte induced inflammatory disorders. Mesenchymal
stem cells (MSCs) have shown to be effective against various inflammatory diseases due to their immunosuppressive
properties. The present study was designed to evaluate the less understood immunomodulatory effect of MSCs on
monocyte proliferation and survival. Method: Primary monocytes were isolated from peripheral human blood using
CD14+ monocyte isolation kit. The in house produced umbilical cord MSCs were co-cultured with monocytes
at different ratio and time; assessed for the monocyte viability, proliferation and cell cycle. Results: Mesenchymal
stem cells suppressed monocyte proliferation in a dose-dependent manner. The antiproliferative effect of MSCs was
mediated by cell cycle arrest, whereby monocytes were arrested in the G0/G1 phase of the cell cycle by preventing
them from progress into S and G2/M phases. Although cell cycle arrest could potentially lead to apoptosis; however,
MSCs significantly enhanced the monocytes survival and inhibited apoptosis. Conclusion: Human MSCs inhibit the
stimulated monocyte proliferation without inducing cellular apoptosis at in vitro. These results reveal that MSCs can
be utilised to control monocytes’ quantity during an unwanted immune response to maintain homeostasis.
Mesenchymal stem cells (MSCs) hold a great therapeutic potential for regenerative
medicine and tissue engineering due to inherent immunomodulatory and reparative properties. Hence,
it necessitates a readily available supplyof MSCs to meet the clinical demands adequately. Although,
a human placenta can produce MSCs, the in vitro culture-mediated cellular senescence often affect the
quality of cell product. Thus, the current study has explored the feasibility of basic fibroblast growth
factor (bFGF) to enhance the growth of placenta-derived MSCs (PLC-MSCs). Methods:The basic
fibroblast growth factor (bFGF) was supplemented to optimise the growth of MSCs. The effects of
bFGF on morphology, growth kinetics and cytokine secretion of PLC-MSCs were assessed. Results:
The bFGF supplementation increased the proliferation of PLC-MSCs in a dose-dependent manner and
40 ng/ml showed a high trophism effect on PLC-MSC’s growth. In the presence of bFGF, PLC-MSCs
acquired a small and well-defined morphology that reflect an active proliferative status. BFGF has
induced PLC-MSCs to achieve a shorter doubling time (45 hrs) as compared to the non-supplemented
PLC-MSCs culture (81 hrs). Furthermore, bFGF impelled PLC-MSCs into cell cycle machinery where
a substantial fraction of cells was driven to S and G2/M phases. Amongst, 36 screened cytokines, bFGF
had only altered the secretion of IL-8, IL-6, TNFR1, MMP3 and VEGF. Conclusion:The present study
showed that bFGF supplementation promotes the growth of PLC-MSCs without significantly deviating
from the standard criteria of MSCs. Thus, bFGF could be considered as a potential mitogen to facilitate
the large-scale production of PLC-MSCs.
Introduction: The phenotype and genotype of cancer cells portray hallmarks of cancer which may
have clinical value. Cancer cell lines are ideal models to study and confirm these characteristics. We
previously established two subtracted cDNA libraries with differentially expressed genes from an
acute myeloid leukaemia patient with poor prognosis (PP) and good prognosis (GP). Objective: To
compare gene expression of the leukaemia associated genes with selected biological characteristics
in leukaemia cell lines and normal controls. Methodology: Expression of 28 PP genes associated
with early fetal/embryonic development, HOX-related genes, hematopoiesis and aerobic glycolysis/
hypoxia genes and 36 GP genes involved in oxidative phosphorylation, protein synthesis, chromatin
remodelling and cell motility were examined in B-lymphoid (BV173, Reh and RS4;11) and myeloid
(HL-60, K562) leukaemia cell lines after 72h in culture as well as peripheral blood mononuclear cells
from healthy controls (N=5) using semi-quantitative polymerase chain reaction (PCR) method. Cell
cycle profiles were analysed on flow cytometry while MTT cytotoxicity assay was used to determine
drug resistance to epirubicin. Results: Genes expressed significantly higher in B-lymphoid leukaemia
cell lines compared to healthy controls were mostly of the GP library i.e. oxidative phosphorylation
(3/10), protein synthesis (4/11), chromatin remodelling (3/3) and actin cytoskeleton genes (1/5). Only
two genes with significant difference were from the PP library. Cancer associated genes, HSPA9 and
PSPH (GP library) and BCAP31 (PP library) were significantly higher in the B-lymphoid leukemia cell
lines. No significant difference was observed between myeloid cell lines and healthy controls. This
may also be due heterogeneity of cell lines studied. PBMC from healthy controls were not in cell cycle.
G2/M profiles and growth curves showed B-lymphoid cells just reaching plateau after 72 hour culture
while myeloid cells were declining. IC50 values from cytotoxicity assay revealed myeloid cell lines had
an average 13-fold higher drug resistance to epirubicin compared to B-lymphoid cell lines. Only CCL1,
was expressed at least two-fold higher in myeloid compared to B-lymphoid cell lines. In contrast,
MTRNR2, EEF1A1, PTMA, HLA-DR, C6orf115, PBX3, ENPP4, SELL, and IL3Ra were expressed
more than 2-fold higher in B-lymphoid compared to myeloid cell lines studied here. Conclusion: Thus,
B-lymphoid leukaemia cell lines here exhibited active, proliferating characteristics closer to GP genes.
Higher expression of several genes in B-lymphoid compared to myeloid leukaemia cell lines may be
useful markers to study biological differences including drug resistance between lineages.
Introduction: This study was conducted to determine immunological and metabolic effects of different concentrations of ginger rhizome (Zingiber officinale Roscoe) in streptozotocin (STZ)-nicotinamide (NA) induced diabetic rats.
Methods: Forty-eight fasted male Sprague-Dawley rats were induced diabetes using a single intraperitoneal injection of NA(110 mg/kg b.w.) and STZ (65 mg/kg b.w, 15 min after NA). Diabetic rats orally received either different concentrations (250, 500 and 750 mg/kg body weight) of ginger rhizome suspension or glibenclamide (10 mg/kg body weight) for 6 weeks. Two control diabetic and normal groups were gavaged with only distilled water as a vehicle.
Results: The results indicated that the lower concentrations of ginger modulated body weight, fasting blood glucose, level of triglyceride and tumor necrosis factor-a (TNF-a) (p
Down syndrome (DS) is a genetic condition resulting from triplication of human chromosome (HSA)21. Besides intellectual disability, DS is frequently associated with hypotonia. Satellite cells are the resident cells that provides robust and remarkable regenerative capacity to the skeletal muscles, and its population size has been reported to be disease-associated. However, little is known about the population size of satellite cells in DS and the association of its intrinsic cellular functionality and hypotonia seen in DS. Here, we studied the Ts1Cje mouse, a DS murine model displays the muscle weakness characteristic. Satellite cell populations were immunostained with Pax7 and myonuclei numbers in the Ts1Cje extensor digitorum longus muscle were assessed. Their cellular function was further determined via in vitro assay in high-serum conditioned medium. Subsequently, the in vitro self-renewal, proliferative, and differentiation activities of these myogenic precursor cells were assessed after 24, 48, and 72h using Pax7, MyoD, and Ki67 immunomarkers. Our results showed that the population and functionality of Ts1Cje satellite cell did not differ significantly when compared to the wildtype cells isolated from disomic littermates. In conclusion, our findings indicated that intrinsic cellular functionality of the satellite cells, do not contribute to muscle weakness in Ts1Cje mouse.