PAMAM dendrimer roles in gene delivery methods and stem cell research

Nanotechnology has provided new technological opportunities, which could help in challenges confronting stem cell research. Polyamidoamine (PAMAM) dendrimers, a new class of macromolecular polymers with high molecular uniformity, narrow molecular distribution specific size and shape and highly functionalised terminal surface have been extensively explored for biomedical application. PAMAM dendrimers are also nanospherical, hyperbranched and monodispersive molecules exhibiting exclusive properties which make them potential carriers for drug and gene delivery

The plasticity of gastric cancer cell lines

Cell heterogeneity is a known feature of cancer cell populations. Because of this, cell population behaviour in response to a particular environment may not be replicated in a specific subpopulation. This has prompted a new hypothesis: that cancer cells can undergo phenotypic change to acquire a stem-like cell phenotype. Thus, to determine which sub-population that displays a specific biological function and whether the environment could influence the plasticity of a group of cells within the population is essential. To investigate the potential influence on cell’s plasticity, human gastric cancer cell line SNU-1 was treated with benzo[a]pyrene (BaP), a potent IARC Group I human carcinogen, to induce a phenotypic response. BaP-AhR associated genes (CYPs) (i.e. CYP1a1, CYP1b1, AHR, AHRR, ARNT) and critical genes associated with epithelial to mesenchymal transition (i.e. Snail, TWIST1) and stemness markers (i.e. SOX2, OCT3/4 and NANOG) were examined. We suspected that subpopulations within SNU-1 were involved. Therefore, flow cytometry was used to observe the expression of CD24 and CD166. In unperturbed culture, enriched CD24+ and CD166+ respective cells were found to revert to their original expression phenotype after 72 hours. However, with BaP-treatment, the sorted cells increased surface expression of CD24 and CD166, respectively. Each sorted population (CD24+, CD166+ and CD24-CD166-) showed different regulation of genes associated with stemness and BaP-induced phenotypic change. CTNNB1, a target gene of Wnt/β-catenin signalling pathway, MYC, and EMT-inducer genes were upregulated in the unsorted SNU-1 population and sorted CD24+ (BaP 10-7M to 10-5M) while remained unchanged in CD166+ and CD24-CD166- populations. Moreover, the induced expression of AhR-related and stemness genes in the sorted CD24+ population, potentially indicates that this subpopulation probably contributes to the plasticity of SNU-1. BaP- treatment also mediates changes in stemness expression and enhanced its migrative and invasive capabilities. Thus, the co-existence and interaction of subpopulations within SNU-1 could play a role in cell plasticity and in sustaining key signalling pathway responses and stemness when exposed to BaP. Our data suggest that cell heterogeneity and plasticity of subpopulations within gastric cancer cells could contribute to BaP-induced gastric carcinogenicityOpen Acces

Generation and characterisation of human mesenchymal stem cells derived from umbilical cord and placenta

Mesenchymal stem cells (MSC) have emerged as a great therapeutic potential in regenerative medicine and tissue engineering, hence created a vast demand for its large clinical scale production. In current study, we have generated MSC from human umbilical cord and placenta tissues that are easily accessible and direct comparisons were made in opting for a better alternate source of MSC in replacement of bone marrow. MSC were successfully generated, assessed for the morphological changes; surface protein expression via immunophenotyping; early embryonic stem cell (ESC) transcriptional factor expression via RT-PCR and mesodermal differentiation ability. UC-MSC and PLC-MSC appeared fibroblastic-like cells and expressed the common mesenchymal surface markers. Both MSC expressed the ESC markers and were able to differentiate into adipocytes, osteocytes and chondrocytes upon induction. In comparison, UC-MSC showed a significantly rapid growth kinetic with higher cell yield and shorter doubling time as compared to PLC-MSC. In our findings, both UC-MSC and PLC-MSC shared similar mesenchymal markers and properties however; UC-MSC appears as a better source of MSC as they display superior differentiation potential and growth kinetics than PLC-MSC