Adipose tissue derived stromal cells in a gelatin-based 3D matrix with exclusive ascorbic acid signalling emerged as a novel neural tissue engineering construct: an innovative prototype for soft tissue.

The current study investigated a triad, which comprises of adipose tissue derived stem cells isolated from infrapatellar fat pad and gelatin/polyvinyl alcohol (PVA)-based matrix with exclusive ascorbic acid signalling. Though, the bio-mechanical properties of the gelatin-PVA blended scaffolds in wet condition are equivalent to the ECM of soft tissues in general, in this study, the triad was tested as a model for neural tissue engineering. Apart from being cytocompatible and biocompatible, the porosity of the scaffold has been designed in such a manner that it facilitates the cell signalling and enables the exchange of nutrients and gases. The highly proliferative stem cells from Passage 2 were characterized using both, mesenchymal and embryonic stem cell markers. As an initial exploration the mesenchymal stem cells at Passage 4 were exposed to ascorbic acid and basic fibroblast growth factor signalling for neuronal differentiation in 2D environment independently. The MSCs successfully differentiated and acquired neuron specific markers related to cytoskeleton and synapses. Subsequently, three phases of experiments have been conducted on the 3D gelatin/PVA matrix to prove their efficacy, the growth of stem cells, growth of differentiated neurons and the in situ growth and differentiation of MSCs. The scaffold was conducive and directed MSCs to neuronal lineage under specific signalling. Overall, this organotypic model triad could open a new avenue in the field of soft tissue engineering as a simple and effective tissue construct.

Polymer modified magnetic-luminescent nanocomposites for combined optical imaging and magnetic fluid hyperthermia in cancer therapy: analysis of Mn2+ doping for enhanced heating effect, hemocompatibility and biocompatibility.

Magnetic MnxFe3-xO4 nanoparticles and polymer coated magnetic-luminescent MnxFe3-xO4@(Y,Dy/Eu)VO4 nanocomposites were prepared to study their comparative heat generation efficiency and biocompatibilities. Cubic crystalline phases were obtained for the nanoparticles and cubic-tetragonal biphasic phases were observed for the nanocomposites. The successful doping of Mn2+ was also confirmed by inductively coupled plasma optical emission spectroscopy. The compositions and the surface modification chemistry were confirmed by infrared spectroscopy. The formation of near-spherical and cubic/cuboid nanoparticles was observed from electron microscopy. Comparative analysis of induction heating efficiencies and magnetization values of the synthesized materials was performed for the samples. The samples showed an efficient heating effect under the influence of alternating magnetic field strengths - 3.05 × 106 kA m-1 s-1 and 4.58 × 106 kA m-1 s-1. A higher Mn2+ content was found to possess higher magnetization and perform better in heat generation. The nanocomposites give brilliant color emission on excitation using ultraviolet wavelengths - 300 and 315 nm. Their hydrodynamic radii and zeta potential values indicate good stability of the dispersions. Hemocompatibility studies were carried out to ascertain the effect on red blood cells. The materials were also found to exhibit excellent biocompatibility towards HeLa cell lines. This article will provide a new insight into the use of MnxFe3-xO4 based nanocomposites for magnetic fluid hyperthermia in cancer therapy.

Hypoxic Preconditioning Induces Neuronal Differentiation of Infrapatellar Fat Pad Stem Cells through Epigenetic Alteration.

Hypoxia is considered a key factor in cellular differentiation and proliferation, particularly during embryonic development; the process of early neurogenesis also occurs under hypoxic conditions. Apart from these developmental processes, hypoxia preconditioning or mild hypoxic sensitization develops resistance against ischemic stroke in deteriorating tissues. We therefore hypothesized that neurons resulting from hypoxia-regulated neuronal differentiation could be the best choice for treating brain ischemia, which contributes to neurodegeneration. In this study, infrapatellar fat pad (IFP), an adipose tissue present beneath the knee joint, was used as the stem cell source. IFP-derived stem cells (IFPSCs) are totally adherent and are mesenchymal stem cells. The transdifferentiation protocol involved hypoxia preconditioning, the use of hypoxic-conditioned medium, and maintenance in maturation medium with α-lipoic acid. The differentiated cells were characterized using microscopy, reverse transcription PCR, real time PCR, and immunocytochemistry. To evaluate the epigenetic reprogramming of IFPSCs to become neuron-like cells, methylation microarrays were performed. Hypoxia preconditioning stabilized and allowed for the translocation of hypoxia inducible factor 1α into the nucleus and induced achaete-scute homologue 1 and doublecortin expression. Following induction, the resultant cells expressed neuronal markers neuron-specific enolase, neurofilament-light chain, growth associated protein 43, synaptosome associated protein 25, and ß-III tubulin. The differentiated neural-lineage cells had functional gene expression pertaining to neurotransmitters, their release, and their receptors. The molecular signaling mechanisms regulated developmental neurogenesis. Furthermore, the in vitro physiological condition regulated neurotransmitter respecification or switching during IFPSC differentiation to neurons. Thus, differentiated neurons were fabricated against the ischemic region to treat neurodegenerative diseases.

Thermally Modified Iron-Inserted Calcium Phosphate for Magnetic Hyperthermia in an Acceptable Alternating Magnetic Field.

Magnetic hyperthermia treatment using calcium phosphate nanoparticles is an evolutionary choice because of its excellent biocompatibility. In the present work, Fe3+ is incorporated into HAp nanoparticles by thermal treatment at various temperatures. Induction heating was examined within the threshold H f value of 4.58 × 106 kA m-1 s-1 (H is the strength of alternating magnetic field and f is the operating frequency) and sample concentration of 10 mg/mL. The temperature-dependent structural modifications are well correlated with the morphological, surface charge, and magnetic properties. Surface charge changes from +10 mV to -11 mV upon sintering because of the diffusion of iron in the HAp lattice. The saturation magnetization has been achieved by sintering the nanoparticles at 400 and 600 °C, which has led to the specific absorption rate of 12.2 and 37.2 W/g, respectively. Achievement of the hyperthermia temperature (42 °C) within 4 min is significant when compared with the existing magnetic calcium phosphate nanoparticles. The systematic investigation reveals that the HAp nanoparticles partially stabilized with FeOOH and biocompatible α-Fe2O3 exhibit excellent induction heating. In vitro tests confirmed the samples are highly hemocompatible. The importance of the present work lies in HAp nanoparticles exhibiting induction heating without compromising the factors such as H f value, low sample concentration, and reduced duration of applied field.

Induction Heating Efficiency of Water-Dispersible Mn0.5Fe2.5O4@YVO4:Eu3+ Magnetic-Luminescent Nanocomposites in an Acceptable ac Magnetic Field: Hemocompatibility and Cytotoxicity Studies.

Not many reports are available on magnetic-luminescent nanocomposites for cancer hyperthermia applications. Further, such nanocomposites on Mn2+-doped iron oxide may be available rather rarely. Studies on the induction heating properties within the threshold magnetic field and frequency factors are still rare. In most cases, magnetic nanoparticles are studied for hyperthermia and lanthanide-doped luminescent nanoparticles for certain biomedical applications. Here, we report on water-dispersible superparamagnetic manganese-doped iron oxide (Mn0.5Fe2.5O4) nanoparticles and a polyethylene glycol6000-coated magnetic-luminescent nanocomposite. The nanocomposite is composed of magnetic Mn0.5Fe2.5O4 (average size 10-20 nm) nanoparticles and red-emitting YVO4:Eu3+ (average size 40-50 nm) nanoparticles. These magnetic nanoparticles and nanocomposites are studied for their induction heating abilities at different acceptable Hf values ( H, strength of alternating magnetic field and f, the operating frequency). The operational Hf values lie in the ranges of 2.15 × 106 to 4.58 × 106 kA m-1 s-1 that are well below the threshold limit of 5 × 106 kA m-1 s-1. A specific absorption rate as high as 132 and 63 W/g, respectively, for Mn0.5Fe2.5O4 and Mn0.5Fe2.5O4@YVO4:Eu3+, can be achieved. The rate of heating and the temperature achieved with time can be tuned with concentrations as well as magnetic constituents in the nanocomposites. Hemocompatibility analysis revealed high blood compatibility with <5% hemolysis. The cytotoxicity analysis in the MCF-7 cell line showed that the cell viability is 74-85% for 0.2-0.5 mg of the magnetic-luminescent nanocomposites. Beyond this concentration, the percentage of cell death is very high. The red-emitting magnetic-luminescent nanocomposites will be useful for in vitro optical imaging and tracking of magnetic nanoparticles. The magnetization analysis showed that the samples have high enough saturation magnetization and low residual magnetization, which is quite suitable for clinical applications. The water dispersibility, hemocompatibility, and cytotoxicity assay in conjunction with their efficient induction heating abilities have shown that these magnetic-luminescent nanocomposites will have potential applications in magnetic fluid hyperthermia and optical imaging.