Biology subjects

Soker, S.

Publications and source records attributed to Soker, S..

3 recordsLinked to original sources

bioRxiv2024

Sex-Specific Cardiovascular Adaptations to Simulated Microgravity in Sprague-Dawley Rats

Men and women have different cardiovascular responses to spaceflight; however few studies have focused on direct comparisons between sexes. Therefore, we investigated cardiovascular system differences, including arterial stiffness between socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hindlimb unloading (HLU) - an analogue for spaceflight-induced microgravity. Two weeks of HLU had no effect on body weight in either male or female rats. The index of arterial stiffness determined by ultrasound, pulse wave velocity (PWV), was greater in the aortic arch and carotid artery of females after HLU versus control females. HLU had no effect on arterial PWV in males. smooth muscle actin, myosin, collagen, elastin, and collagen-to-elastin ratio were not different in rats of either sex in response to HLU. HLU exposure did not alter individual collagen fiber characteristics in studied groups. The levels of G protein-coupled estrogen receptor (GPER) were lower in the aorta of SD females exposed to HLU compared with female controls but not in males. These changes were associated with lower PPAR {gamma} and increased oxidative stress markers (8-hydroxy-2-deoxyguanosine and p47phox) in the females. Diastolic cardiac function was altered in females after HLU versus control females. GPER agonist, G1 prevented the increase in pulse wave velocity and 8-hydroxy-2-deoxyguanosine, without altering PPAR {gamma} or p47phox. Our data revealed that lower GPER in the HLU females contributes to the development of arterial stiffness, and that the SD rat is a suitable model to study the cardiovascular response of females to HLU.

physiology↗

bioRxiv2021

Engineering a thixotropic and biochemically tunable hyaluronan and collagen bioink for biofabrication of multiple tissue construct types

The field of three-dimensional (3D) bioprinting has advanced rapidly in recent years. Significant reduction in the costs associated with obtaining functional 3D bioprinting hardware platforms is both a cause and a result of these advances. As such, there are more laboratories than ever integrating bioprinting methodologies into their research. However, there is a lack of standards in the field of biofabrication governing any requirements or characteristics to support cross-compatibility with biomaterial bioinks, hardware, and different tissue types. Here we describe a modular extracellular matrix (ECM) inspired bioink comprised of collagen and hyaluronic acid base components that: 1) employ reversible internal hydrogen bonding forces to generate thixotropic materials that dynamically reduce their elastic moduli in response to increased shear stress, thus enabling increased compatibility with printing hardware; and 2) modular addons in the form of chemically-modified fibronectin and laminin that when covalently bound within the bioink support a variety of tissue types, including liver, neural, muscle, pancreatic islet, and adipose tissue. These features aim to accelerate the deployment of such bioinks for tissue engineering of functional constructs in the hands of various end users.

bioengineering↗

bioRxiv2019

Simulating the human tumor microenvironment in colorectal cancer organoids in vitro and in vivo

The tumor microenvironment (TME) plays a significant role in cancer growth and metastasis. Bioengineered models of the TME will advance our understanding of cancer progression and facilitate identification of novel anti-cancer therapeutics that target TME components such as extracellular matrix (ECM) and stromal cells. However, most current in vitro models fail to recapitulate the extensive features of the human tumor stroma, especially ECM architecture, and are not exposed to intact body physiology. On the other hand, in vivo animal models do not accurately capture human tumor architecture. Using the features of biopsied colorectal cancer (CRC) tissue as a guide, we address these deficiencies by creating human organoids containing a colonic stromal ECM layer and CRC spheroids. Organoids were studied in vitro and upon implantation in mice for 28 days. We show that the stromal ECM micro-architecture, generated in vitro, was maintained in vivo for at least 28 days. Furthermore, comparisons with biopsied CRC tumors revealed that organoids with orderly structured TMEs induce an epithelial phenotype in CRC cells, similar to low-grade tumors, compared to a mesenchymal phenotype observed in disordered TMEs, similar to high-grade tumors. Altogether, these results are the first demonstration of replicating the human tumor ECM architecture in biofabricated tumor organoids under ex vivo and in vivo conditions.

cancer biology↗