Novel thermosensitive poly (N-isopropylacrylamide-co-vinylpyrrolidone-co-methacrylic acid) nanosystems for delivery of natural products

The purpose of this research was to synthesize polymer based smart nanosystems for delivery of important bioactive natural products such as sesquiterpene coumarin derivatives of ferula szowitsiana, farnesiferol C as a potent anticancer. To this aim, polymeric micelles were prepared using N-isopropylacrylamide (NIPAAM), vinyl pyrrolidone (VP) and methacrylate (MAA) as monomers which were cross-linked with N, N-methylene bis-acrylamide (MBA). The molar ratio of the PNIPAAm: VP: MAA group was 75.7:9.5:14.8. These micelles were further characterized upon their physicochemical properties using particle size analyzer, FT-IR, H-/C-NMR, HPLC. Particle size analyzer resulted in ~500 nm micelles with ~95% drug entrapments. Drug release from the polymeric micelles after 300 hours at 37°C and 40°C were 60 and 98 %, respectively. Upon these findings, it is proposed that the P (N-isopropylacrylamide-co-Methacrylic acid-co-Vinylpyrrolidone) micelles may be considered as thermosensitive delivery nanosystem.Keywords: N-isopropylacrylamide; Thermosensitive; Nanoparticles; Farnesiferol C; Amphiphilic polymers

Responsive cell–material interfaces

Major design aspects for novel biomaterials are driven by the desire to mimic more varied and complex properties of a natural cellular environment with man-made materials. The development of stimulus responsive materials makes considerable contributions to the effort to incorporate dynamic and reversible elements into a biomaterial. This is particularly challenging for cell–material interactions that occur at an interface (biointerfaces); however, the design of responsive biointerfaces also presents opportunities in a variety of applications in biomedical research and regenerative medicine. This review will identify the requirements imposed on a responsive biointerface and use recent examples to demonstrate how some of these requirements have been met. Finally, the next steps in the development of more complex biomaterial interfaces, including multiple stimuli-responsive surfaces, surfaces of 3D objects and interactive biointerfaces will be discussed

Bioengineering the Human Muscle Stem-Cell Niche for Therapeutic Applications

In spite of decades of research, no feasible method for obtaining sufficient numbers of uncommitted muscle stem cells (MuSCs) for therapy of degenerative muscle diseases exists. One of the most fundamental problems associated with stem cell therapy of muscle is that removal of MuSCs from their tissue microenvironment and expansion in conventional culture induces their terminal commitment to myogenic differentiation. This in-vitro loss of stemness impairs the long-term engraftment potential of MuSCs and renders them unsuitable for stem cell therapy. In another disease relevant context, aging, dramatic changes in the functionality of MuSCs have been shown to depend on an altered composition of their microenvironment. Thus, muscle progenitors are fundamentally dependent on their local environment, commonly known as the âstem cell niche", and a better understanding of its role in guiding stem cell function is highly relevant for the development of therapies for aging and muscle diseases. The muscle stem cell niche is composed of diverse cellular and acellular elements, including different supportive cell types, growth factors and extracellular matrix, and as outlined above, is critical for maintaining healthy stem cell characteristics such as the capacity for self-renewal, commitment, and differentiation. Using molecular biology approaches, we decided to interrogate (I) the role of the cellular environment on stem cell commitment, (II) to test whether, in a physiological context, the systemic circulation has niche-independent effects on MuSC stemness, and (III) to study a population of MuSC-supportive cells that is affected by the aging process. In the first study of this thesis, we have successfully developed an organoid-like-approach for the scalable derivation of uncommitted MuSCs from human induced pluripotent stem cells (iPSCs) in a biologically faithful cellular 3D-environment in suspension embryoids. To this end, we employed human iPSCs and a spectrum of immortalized cell lines to screen for 3D-aggregation conditions promoting mesoderm formation and subsequent specification to the myogenic lineage without the parallel upregulation of myogenic commitment markers. Compared to myogenic cells derived from adult human skeletal muscle, this niche-mimetic embryoid derived progenitors display significantly enhanced engraftment into the muscle stem cell position peripheral to muscle fibers, and restoration of dystrophin expression when transplanted into muscles of a mouse model of Duchenne muscular dystrophy. In a second study, we present a novel method for encapsulation of human muscle progenitors in highly diffusible polyethersulfone hollow fiber capsules to identify highly specific "transcriptional-signature" induced by systemic aging in-vivo. This technique allows to study the systemic circulation in health, disease and aging at an unprecedented level in human cell types of choice. Finally, in our third study, we investigated the cellular cross-talk between muscle stem cells and non-myogenic niche-based cell type, called fibro/adipogenic progenitors (FAPs). Interestingly, the support-function and the cross-talk with stem cells are dramatically impaired in aged FAPs. We demonstrate that this mechanism can be targeted to rejuvenate myogenesis. Taken together, "mimicking" the physicochemical-interactions of MuSCs with their niche-resident cell types, represents a powerful opportunity to manipulate MuSC function in aging and disease

Characterization of Streptomyces Isolates with UV, FTIR Spectroscopy and HPLC Analyses

Introduction: Streptomyces, gram-positive and aerobic bacteria, are distinguished genus of Actinomycetes. This economically important genus is well studied owing to its capacity in producing more than 70% of antibiotics. In fact, need for novel, safe and more efficient antibiotics is a key challenge to the pharmaceutical industry today, moreover, increase in opportunistic infections in the immune compromised host has influenced this demand. Nowadays, evaluating morphological and biochemical differences as well as studying streptomyces genetic diversity via molecular indicators seem to be the most common method for screening this genus. Methods: In this research we evaluate the potential of antibiotic production and characterize the UV and FTIR spectroscopy and HPLC (High performance liquid chromatography) analysis pattern of streptomyces from various locations in northwest of Iran. Regarding this, 30 soil samples were collected randomly from different zones of northwest region of Iran. Then, following the extraction of secondary metabolite, the UV and FTIR spectroscopy analysis was carried out for characterization of the various extracts. Results: Considering the coordinate analysis of UV and FTIR spectroscopy pattern, the isolate G614C1 with substantial antimicrobial activity exhibited absorption at 3411 cm-1 which is indicator of hydroxyl groups, absorption at 2856 and 2915 cm-1 indicating hydrocarbon chassis, and absorption at 1649 cm-1 indicating a double bond of polygenic compound. Conclusion: These results highlight the importance of streptomyces isolates in antibiotic production. HPLC confirmed the production when compared with standards

Osmolarity: A hidden factor in Nanotoxicology

In the field of drug delivery, long circulating nanocarriers in the blood have many advantages such as targeted drug delivery and sustained release. Based on our current knowledge, evaluation of the effect of long circulating nanocarriers in the blood stream on osmolarity of plasma has not been reported before. In this study, osmotic pressure developed by some commercially available nanocarriers was estimated based on Van't Hoff equation. It is noteworthy that theoretically, nanocarriers do not have any significant effect on osmolarity of plasma. However, it is worth being evaluated experimentally in order to be taken into account in future studies

Impacts of quantum dots in molecular detection and bioimaging of cancer

Introduction: A number of assays have so far been exploited for detection of cancer biomarkers in various malignancies. However, the expression of cancer biomarker(s) appears to be extremely low, therefore accurate detection demands sensitive optical imaging probes. While optical detection using conventional fluorophores often fail due to photobleaching problems, quantum dots (QDs) offer stable optical imaging in vitro and in vivo. Methods: In this review, we briefly overview the impacts of QDs in biology and its applications in bioimaging of malignancies. We will also delineate the existing obstacles for early detection of cancer and the intensifying use of QDs in advancement of diagnostic devices. Results: Of the QDs, unlike the II-VI type QDs (e.g., cadmium (Cd), selenium (Se) or tellurium (Te)) that possess inherent cytotoxicity, the I-III-VI 2 type QDs (e.g., AgInS2, CuInS2, ZnS-AgInS2) appear to be less toxic bioimaging agents with better control of band-gap energies. As highly-sensitive bioimaging probes, advanced hybrid QDs (e.g., QD-QD, fluorochrome-QD conjugates used for sensing through fluorescence resonance energy transfer (FRET), quenching, and barcoding techniques) have also been harnessed for the detection of biomarkers and the monitoring of delivery of drugs/genes to the target sites. Antibody-QD (Ab-QD) and aptamer-QD (Ap-QD) bioconjugates, once target the relevant biomarker, can provide highly stable photoluminescence (PL) at the target sites. In addition to their potential as nanobiosensors, the bioconjugates of QDs with homing devices have successfully been used for the development of smart nanosystems (NSs) providing targeted bioimaging and photodynamic therapy (PDT). Conclusion: Having possessed great deal of photonic characteristics, QDs can be used for development of seamless multifunctional nanomedicines, theranostics and nanobiosensors

Neural priming of adipose-derived stem cells by cell-imprinted substrates

Cell-imprinting technology is a novel method for directing stem cell fate using substrates molded from target cells. Here, we fabricated and studied cell-imprinted substrates for neural priming in human adipose-derived stem cells in the absence of chemical cues. We molded polydimethylsiloxane (PDMS) silicone substrates on fixed differentiated neural progenitor cells (ReNcellTM VM). The ReNcellTM cell line consists of immortalized human neural progenitor cells that are capable to differentiate into neural cells. The fabricated cell-imprinted silicone substrates represent the geometrical micro- and nanotopology of the target cell morphology. During the molding procedure, no transfer of cellular proteins was detectable. In the first test with undifferentiated ReNcellTM VM cells, the cell-imprinted substrates could accelerate neural differentiation. With adipose-derived stem cells cultivated on the imprinted substrates, we observed modifications of cell morphology, shifting from spread to elongated shape. Both immunofluorescence and quantitative gene expression analysis showed upregulation of neural stem cell and early neuronal markers. Our study, for the first time, demonstrated the effectiveness of cell-imprinted substrates for neural priming of adipose-derived stem cells for regenerative medicine applications

Nutritional Control of Intestinal Stem Cells in Homeostasis and Tumorigenesis

Food and nutrition have a profound impact on organismal health and diseases, and tissue-specific adult stem cells play a crucial role in coordinating tissue maintenance by responding to dietary cues. Emerging evidence indicates that adult intestinal stem cells (ISCs) actively adjust their fate decisions in response to diets and nutritional states to drive intestinal adaptation. Here, we review the signalingmechanismsmediating the dietary responses imposed by caloric intake and nutritional composition (i.e., macronutrients and micronutrients), fasting-feeding patterns, diet-induced growth factors, and microbiota on ISCs and their relevance to the beginnings of intestinal tumors

Possibilities in Germ Cell Research: An Engineering Insight

Germ cells (GCs) are responsible for fertility and disruptions in their development or function cause infertility. However, current knowledge about the diverse mechanisms involved in GC development and function is still in its infancy. This is mainly because there are low numbers of GCs, especially during embryonic development. A deeper understanding of GCs would enhance our ability to produce them from stem cells. In addition, such information would enable the production of healthy gametes for infertile couples. In this regard, pluripotent stem cells (PSCs) demonstrated a promising ability to produce GCs in vitro. In this review, we highlight recent advances in the field of tissue engineering that suggest novel strategies to enhance GC research

Regulation of stem cell fate by nanomaterial substrates

Stem cells are increasingly studied because of their potential to underpin a range of novel therapies, including regenerative strategies, cell type-specific therapy and tissue repair, among others. Bionanomaterials can mimic the stem cell environment and modulate stem cell differentiation and proliferation. New advances in these fields are presented in this review. This work highlights the importance of topography and elasticity of the nano-/micro-environment, or niche, for the initiation and induction of stem cell differentiation and proliferation