Multifaceted applications of nanomaterials in cell engineering and therapy

Nanomaterials with superior physiochemical properties have been rapidly developed and integrated in every aspect of cell engineering and therapy for translating their great promise to clinical success. Here we demonstrate the multifaceted roles played by innovatively-designed nanomaterials in addressing key challenges in cell engineering and therapy such as cell isolation from heterogeneous cell population, cell instruction in vitro to enable desired functionalities, and targeted cell delivery to therapeutic sites for prompting tissue repair. The emerging trends in this interdisciplinary and dynamic field are also highlighted, where the nanomaterial-engineered cells constitute the basis for establishing in vitro disease model; and nanomaterial-based in situ cell engineering are accomplished directly within the native tissue in vivo. We will witness the increasing importance of nanomaterials in revolutionizing the concept and toolset of cell engineering and therapy which will enrich our scientific understanding of diseases and ultimately fulfill the therapeutic demand in clinical medicine.     

Effects of N6, 2′-O-dibutyryl cyclic adenosine monophosphate and the leukemia inhibitory factor on embryo development of the giant freshwater prawn,Macrobrachium rosenbergii

Summary

The effects of N⁶, 2′-O-dibutyryl cyclic adenosine monophosphate (dbcAMP) and the leukemia inhibitory factor (LIF) on embryo development of the giant freshwater prawn, Macrobrachium rosenbergii, were studied. Embryos 1.5 days old were cultured in vitro in 15% artificial seawater supplemented with 0.05 mM, 0.1 mM or 0.5 mM dbcAMP, or with 10 ng/ml, 20 ng/ml or 50 ng/ml LIF for 2 days. No differences in the morphology or growth of the embryos between the supplemented and the control groups were observed. The developmental rates as revealed by the eye formation rates were not altered with either supplement. The survival rates of the embryos declined during the course of development; and, again, the rates were not altered when supplemented with dbcAMP or LIF. Although there were no significant changes in the eye formation rate in embryos supplemented with 0.05 mM dbcAMP, an increase in the hatching rate was found. In contrast, supplementation with LIF did not improve the hatching rates. Germ cell development seemed to be most affected. The number of primordial germ cells (PGCs), the progenitors of gametes, was significantly increased with both dbcAMP and LIF supplementation. However, supplementation with 0.05 mM dbcAMP and 10 ng/ml LIF combined did not provide any additional effect on this feature.     

Fatty acid synthase causes drug resistance by inhibiting TNF-α and ceramide production

Fatty acid synthase (FASN) is a key enzyme in the synthesis of palmitate, the precursor of major nutritional, energetic, and signaling lipids. FASN expression is upregulated in many human cancers and appears to be important for cancer cell survival. Overexpression of FASN has also been found to associate with poor prognosis and higher risk of recurrence of human cancers. Indeed, elevated FASN expression has been shown to contribute to drug resistance. However, the mechanism of FASN-mediated drug resistance is currently unknown. In this study, we show that FASN overexpression causes resistance to multiple anticancer drugs via inhibiting drug-induced ceramide production, caspase 8 activation, and apoptosis. We also show that FASN overexpression suppresses tumor necrosis factor-α production and nuclear factor-κB activation as well as drug-induced activation of neutral sphingomyelinase. Thus, TNF-α may play an important role in mediating FASN function in drug resistance.     

Lymphatic Endothelial Differentiation in Pulmonary Lymphangioleiomyomatosis Cells

Pulmonary lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm affecting almost exclusively women of childbearing age. LAM belongs to the family of perivascular epithelioid cell tumors, characterized by spindle and epithelioid cells with smooth muscle and melanocytic differentiation. LAM cells infiltrate the lungs, producing multiple, bilateral lesions rich in lymphatic channels and forming cysts, leading to respiratory insufficiency. Here we used antibodies against four lymphatic endothelial markers—podoplanin (detected by D2-40), prospero homeobox 1 (PROX1), vascular endothelial growth factor receptor 3 (VEGFR-3), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1)—to determine whether LAM cells show lymphatic differentiation. Twelve of 12 diagnostic biopsy specimens (early-stage LAM) and 19 of 19 explants (late-stage LAM) showed immunopositivity for D2-40 in most neoplastic cells. PROX1, VEGFR-3, and LYVE1 immunoreactivity varied from scarce in the early stage to abundant in the late stage. Lymphatic endothelial, smooth muscle, and melanocytic markers were partially co-localized. These findings indicate that lymphatic endothelial differentiation is a feature of LAM and provide evidence of a previously unidentified third lineage of differentiation in this neoplasm. This study has implications for the histological diagnosis of LAM, the origin of the neoplastic cells, and potential future treatment with drugs targeting lymphangiogenesis.     

Growth Arrest Specific 1 (GAS1) Is Abundantly Expressed in the Adult Mouse Central Nervous System

Growth arrest specific 1 (GAS1) is a pleiotropic protein that induces apoptosis and cell arrest in different tumors, but it is also involved in the development of the nervous system and other tissues and organs. This dual ability is likely caused by its capacity to interact both by inhibiting the intracellular signaling cascade induced by glial cell-line derived neurotrophic factor and by facilitating the activity of the sonic hedgehog pathway. The presence of GAS1 mRNA has been described in adult mouse brain, and here we corroborated this observation. We then proceeded to determine the distribution of the protein in the adult central nervous system (CNS). We detected, by western blot analysis, expression of GAS1 in olfactory bulb, caudate-putamen, cerebral cortex, hippocampus, mesencephalon, medulla oblongata, cerebellum, and cervical spinal cord. To more carefully map the expression of GAS1, we performed double-label immunohistochemistry and noticed expression of GAS1 in neurons in all brain areas examined. We also observed expression of GAS1 in astroglial cells, albeit the pattern of expression was more restricted than that seen in neurons. Briefly, in the present article, we report the widespread distribution and cellular localization of the GAS1 native protein in adult mammalian CNS.     

Behavioural salinity preferences of juvenile green sturgeon Acipenser medirostris acclimated to fresh water and full‐strength salt water

To quantify the salinity preference of juvenile green sturgeon Acipenser medirostris, two groups of A. medirostris [140 days post hatch (dph); total length (L_T) 38·0–52·5 cm] were acclimated to either near fresh water (mean ± s.e . salinity = 3·2 ± 0·6) or full‐strength salt water (34·1 ± 1·2) over 8 weeks. Following acclimation, the two groups were divided into experimental and control groups, where experimental A. medirostris from both freshwater and saltwater acclimations were individually introduced (200–220 dph) into a rectangular salinity‐preference flume (maximum salinity gradient: 5–33). Control A. medirostris were presented with only their acclimation water (fresh water or salt water) on both sides of the flume. It was demonstrated that A. medirostris acclimated to both salt water and fresh water spent a significantly greater amount of time on the side of the testing area with the highest salinity concentration (P < 0·05 and P < 0·001, respectively) while control A. medirostris spent an equal amount of time on each side of the flume. These findings indicate that juvenile A. medirostris are not only capable of detecting salt water within the first year of their lives but perhaps are actively seeking out saline environments as they move through a watershed. Establishing A. medirostris salinity preferences provides a better understanding of the early life history of this threatened species, shedding light on possible outmigration timing.