Tissue and cell interactions in mammalian PGC development

ABSTRACT Primordial germ cells (PGCs) form early in embryo development and are crucial precursors to functioning gamete cells. Considerable research has focussed on identifying the transcriptional characteristics and signalling pathway requirements that confer PGC specification and development, enabling the derivation of PGC-like cells (PGCLCs) in vitro using specific signalling cocktails. However, full maturation to germ cells still relies on co-culture with supporting cell types, implicating an additional requirement for cellular- and tissue-level regulation. Here, we discuss the experimental evidence that highlights the nature of intercellular interactions between PGCs and neighbouring cell populations during mouse PGC development. We posit that the role that tissue interactions play on PGCs is not limited solely to signalling-based induction but extends to coordination of development by robust regulation of the proportions and position of the cells and tissues within the embryo, which is crucial for functional germ cell maturation. Such tissue co-development provides a dynamic, contextual niche for PGC development. We argue that there is evidence for a clear role for inter-tissue dependence of mouse PGCs, with potential implications for generating mammalian PGCLCs in vitro.

Developing Mg-Zn-Fish Bone Derived Hydroxyapatite Composites for Biomedical Applications: In vitro Degradation Studies

The study of magnesium (Mg) based biomaterials has emerged as a potential research area in recent times. Controlling the rapid corrosion and improving the implant-tissue interface kinetics for better tissue regeneration are the prime interests behind developing novel Mg-based composites. In the current work, the metal matrix composites of Mg-Zn, dispersed with nano-hydroxyapatite derived from fish bones (fHA), were produced by powder metallurgy route. The powders were mixed with the help of ball milling in the presence of ethanol and then sintered at 440 °C. From the microstructural studies, micro-lamellar morphology was noticed for the sintered compacts due to the flake-like morphology of the milled powders. The sintered compacts were then subjected to in vitro biodegradation studies in simulated conditions for one week. From the results, the presence of fHA was found to be highly influential in increasing the rate of mineral deposition on the surface of the composites. These higher mineral depositions protected the surface of the composites from further degradation. The results demonstrate that adding fHA to Mg accelerates biomineralization and controls degradation, leading to better implant-tissue interactions.

Bioactive Titanium-Hydroxyapatite Composites by Powder Metallurgy Route

Titanium (Ti) and its alloys have become the most promising biomaterials due to their low elastic modulus, high corrosion resistance, and relatively long-lasting ability in a physiological environment. Bioactive implants enhance the tissue interactions at the surface of the implants and promote a higher healing rate. However, titanium exhibits bio-inert nature. Hence in the present study, hydroxyapatite (HA), a well-known bioceramic, has been selected to disperse into Ti with an aim to develop bioactive Ti-based implants. Ti-HA composites with 5% and 10% HA were successfully produced by high-energy ball milling for 20 h followed by sintering (at 850 °C). Fine-grained composites were successfully produced and were found to be free from any impurities. The composites were immersed in simulated body fluid (SBF) for 4 weeks to investigate the in vitro bioactivity. From the XRD studies and scanning electron microscope observations, the presence of HA in the composite enhanced the bioactivity as reflected with higher Ca/P mineral phases on the surface of the composites compared with pure Ti substrate. From the results, it can be concluded that the bioactive nature of Ti can be enhanced by reinforcing HA to manufacture medical implants with a higher healing rate.

A Systems-Level Analysis of Total-Body PET Data Reveals Complex Skeletal Metabolism Networks in vivo

Bone is now regarded to be a key regulator of a number of metabolic processes, in addition to the regulation of mineral metabolism. However, our understanding of complex bone metabolic interactions at a systems level remains rudimentary. in vitro molecular biology and bioinformatics approaches have frequently been used to understand the mechanistic changes underlying disease at the cell level, however, these approaches lack the capability to interrogate dynamic multi-bone metabolic interactions in vivo. Here we present a novel and integrative approach to understand complex bone metabolic interactions in vivo using total-body positron emission tomography (PET) network analysis of murine 18F-FDG scans, as a biomarker of glucose metabolism in bones. In this report we show that different bones within the skeleton have a unique glucose metabolism and form a complex metabolic network, which could not be identified using single tissue simplistic PET standard uptake values analysis. The application of our approach could reveal new physiological and pathological tissue interactions beyond skeletal metabolism, due to PET radiotracers diversity and the advent of clinical total-body PET systems.

Drosophila Larval Models of Invasive Tumorigenesis for In Vivo Studies on Tumour/Peripheral Host Tissue Interactions during Cancer Cachexia

Cancer cachexia is a common deleterious paraneoplastic syndrome that represents an area of unmet clinical need, partly due to its poorly understood aetiology and complex multifactorial nature. We have interrogated multiple genetically defined larval Drosophila models of tumourigenesis against key features of human cancer cachexia. Our results indicate that cachectic tissue wasting is dependent on the genetic characteristics of the tumour and demonstrate that host malnutrition or tumour burden are not sufficient to drive wasting. We show that JAK/STAT and TNF-α/Egr signalling are elevated in cachectic muscle and promote tissue wasting. Furthermore, we introduce a dual driver system that allows independent genetic manipulation of tumour and host skeletal muscle. Overall, we present a novel Drosophila larval paradigm to study tumour/host tissue crosstalk in vivo, which may contribute to future research in cancer cachexia and impact the design of therapeutic approaches for this pathology.