Hand-held electron spin resonance scanner for subcutaneous oximetry using OxyChip.

Purpose: Electron spin resonance (ESR) is used to measure oxygen partial pressure (pO) in biological media with many clinical applications. Traditional clinical ESR involves large magnets that encompass the subject of measurement. However, certain applications might benefit from a scanner operating within local static magnetic fields.

ECM-based bioactive microencapsulation significantly improves islet function and graft performance.

Microencapsulation is a promising strategy to prolong the survival and function of transplanted pancreatic islets for diabetes therapy, albeit its translation has been impeded by incoherent graft performance. The use of decellularized ECM has lately gained substantial research momentum due to its innate capacity to augment the function of cells originating from the same tissue type. In the present study, the advantages of both these approaches are leveraged in a porcine pancreatic ECM (pECM)-based microencapsulation platform, thus significantly enhancing murine pancreatic islet performance.

Cultured meat platform developed through the structuring of edible microcarrier-derived microtissues with oleogel-based fat substitute.

With the increasing global demand for meat, cultured meat technologies are emerging, offering more sustainable solutions that aim to evade a future shortage of meat. Here, we demonstrate a cultured meat platform composed of edible microcarriers and an oleogel-based fat substitute. Scalable expansion of bovine mesenchymal stem cells on edible chitosan-collagen microcarriers is optimized to generate cellularized microtissues.

Extracellular Matrix Hydrogels Originated from Different Organs Mediate Tissue-Specific Properties and Function.

Porcine extracellular matrix (pECM)-derived hydrogels were introduced, in recent years, aiming to benefit the pECM's microstructure and bioactivity, while controlling the biomaterial's physical and mechanical properties. The use of pECM from different tissues, however, offers tissue-specific features that can better serve different applications. In this study, pECM hydrogels derived from cardiac, artery, pancreas, and adipose tissues were compared in terms of composition, structure, and mechanical properties.

Nanoghosts: Mesenchymal Stem cells derived nanoparticles as a unique approach for cartilage regeneration.

Osteoarthritis (OA) is a chronic degenerative disease, which affects the joints and is characterized by inflammation, cartilage loss and bone changes. Nowadays, there are no treatments for OA, and current therapies are focused on relieving the symptoms. As a new therapy approach, micro and nanoparticles have been extensively explored and among all the studied particles, the use of cell-membrane-based particles is expanding.

Nano-ghosts: Novel biomimetic nano-vesicles for the delivery of antisense oligonucleotides.

Antisense oligonucleotides (ASOs) carry an enormous therapeutic potential in different research areas, however, the lack of appropriate carriers for their delivery to the target tissues is hampering their clinical translation. The present study investigates the application of novel biomimetic nano-vesicles, Nano-Ghosts (NGs), for the delivery of ASOs to human mesenchymal stem cells (MSCs), using a microRNA inhibitor (antimiR) against miR-221 as proof-of-concept. The integration of this approach with a hyaluronic acid-fibrin (HA-FB) hydrogel scaffold is also studied, thus expanding the potential of NGs applications in regenerative medicine.

Extracellular Vesicles Reflect the Efficacy of Wheatgrass Juice Supplement in Colon Cancer Patients During Adjuvant Chemotherapy.

Introduction: Colorectal cancer (CC) is the third most common type of cancer, accounting for 10% of all cancer cases. Adjuvant chemotherapy is recommended in stages II-III CC. Wheatgrass juice (WGJ) from wheat seeds has high nutritional values, may induce synergistic benefits to chemotherapy and may attenuate chemotherapy-related side effects.

Robust Fabrication of Composite 3D Scaffolds with Tissue-Specific Bioactivity: A Proof-of-Concept Study.

The basic requirement of any engineered scaffold is to mimic the native tissue extracellular matrix (ECM). Despite substantial strides in understanding the ECM, scaffold fabrication processes of sufficient product robustness and bioactivity require further investigation, owing to the complexity of the natural ECM. A promising bioacive platform for cardiac tissue engineering is that of decellularized porcine cardiac ECM (pcECM, used here as a soft tissue representative model).

Porcine arterial ECM hydrogel: Designing an in vitro angiogenesis model for long-term high-throughput research.

The field of angiogenesis research provides deep understanding regarding this important process, which plays fundamental roles in tissue development and different abnormalities. In vitro models offer the advantages of low-cost high-throughput research of angiogenesis while sparing animal lives, and enabling the use of human cells. Nevertheless, prevailing in vitro models lack stability and are limited to a few days' assays.

Nano-Ghosts: Biomimetic membranal vesicles, technology and characterization.

Currently, nano-carriers for anti-cancer drug delivery are complex systems, which struggle with immunogenicity and enhanced permeability effect (EPR)-related problems that halt the clinical translation of many therapeutics. Consequently, a rapidly growing field of research has been focusing on biomimetic nano-vesicles (BNVs) as an effective delivery alternative. Nevertheless, the translation of many BNVs is limited due to scalability problems, inconsistent production process, and insufficient loading efficiency.

Engineered heart tissue models from hiPSC-derived cardiomyocytes and cardiac ECM for disease modeling and drug testing applications.

Cardiac tissue engineering provides unique opportunities for cardiovascular disease modeling, drug testing, and regenerative medicine applications. To recapitulate human heart tissue, we combined human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with a chitosan-enhanced extracellular-matrix (ECM) hydrogel, derived from decellularized pig hearts. Ultrastructural characterization of the ECM-derived engineered heart tissues (ECM-EHTs) revealed an anisotropic muscle structure, with embedded cardiomyocytes showing more mature properties than 2D-cultured hiPSC-CMs.

Pretreating Mesenchymal Stem Cells with Cancer Conditioned-Media or Proinflammatory Cytokines Changes the Tumor and Immune Targeting by Nanoghosts Derived from these Cells.

Nanoghosts (NGs) are nanovesicles reconstructed from the cytoplasmic membranes of mesenchymal stem cells (MSCs). By retaining MSC membranes, the NGs retain the ability of these cells to home in on multiple tumors, laying the foundations, thereby, for the development of a targeted drug delivery platform. The susceptibility of MSCs to functional changes, following their exposure to cytokines or cancer-derived conditioned-media (CM), presents the opportunity to modify the NGs by conditioning their source cells.

3D Structure and Processing Methods Direct the Biological Attributes of ECM-Based Cardiac Scaffolds.

High hopes are held for cardiac regenerative therapy, driving a vast research effort towards the development of various cardiac scaffolds using diverse technologies and materials. Nevertheless, the role of factors such as fabrication process and structure in determining scaffold's characteristics is yet to be discovered. In the present study, the effects of 3D structure and processing method on cardiac scaffolds are addressed using three distinct scaffolds made through different production technologies from the same biomaterial: decellularized porcine cardiac extracellular matrix (pcECM).

Radiolabeling of cell membrane-based nano-vesicles with C-linoleic acid for robust and sensitive quantification of their biodistribution.

The rapid development of biomimetic cell membrane-based nanoparticles is still overshadowed by many practical challenges, one of which is the difficulty to precisely measure the biodistribution of such nanoparticles. Currently, this challenge is mostly addressed using fluorescent techniques with limited sensitivity, or radioactive labeling methods, which rarely account for the nanoparticles themselves, but their payloads instead. Here we report the development of a robust method for the innate radioactive labeling of cells and membrane-based nanoparticles and their consequent sensitive detection and biodistribution measurements.

Biological and mechanical interplay at the Macro- and Microscales Modulates the Cell-Niche Fate.

Tissue development, regeneration, or de-novo tissue engineering in-vitro, are based on reciprocal cell-niche interactions. Early tissue formation mechanisms, however, remain largely unknown given complex in-vivo multifactoriality, and limited tools to effectively characterize and correlate specific micro-scaled bio-mechanical interplay. We developed a unique model system, based on decellularized porcine cardiac extracellular matrices (pcECMs)-as representative natural soft-tissue biomaterial-to study a spectrum of common cell-niche interactions.

Therapy-Educated Mesenchymal Stem Cells Enrich for Tumor-Initiating Cells.

Stromal cells residing in the tumor microenvironment contribute to the development of therapy resistance. Here we show that chemotherapy-educated mesenchymal stem cells (MSC) promote therapy resistance via cross-talk with tumor-initiating cells (TIC), a resistant tumor cell subset that initiates tumorigenesis and metastasis. In response to gemcitabine chemotherapy, MSCs colonized pancreatic adenocarcinomas in large numbers and resided in close proximity to TICs.

Delivery of the gene encoding the tumor suppressor Sef into prostate tumors by therapeutic-ultrasound inhibits both tumor angiogenesis and growth.

Carcinomas constitute over 80% of all human cancer types with no effective therapy for metastatic disease. Here, we demonstrate, for the first time, the efficacy of therapeutic-ultrasound (TUS) to deliver a human tumor suppressor gene, hSef-b, to prostate tumors in vivo. Sef is downregulated in various human carcinomas, in a manner correlating with tumor aggressiveness.

Restoring the biophysical properties of decellularized patches through recellularization.

Various extracellular matrix (ECM) scaffolds, isolated through decellularization, were suggested as ideal biomimetic materials for 'Functional tissue engineering' (FTE). The decellularization process comprises a compromise between damaging and preserving the ultrastructure and composition of ECM-previously shown to affect cell survival, proliferation, migration, organization, differentiation and maturation. Inversely, the effects of cells on the ECM constructs' biophysical properties, under physiological-like conditions, remain still largely unknown.

Ultrasound-Mediated Mesenchymal Stem Cells Transfection as a Targeted Cancer Therapy Platform.

Mesenchymal stem cells (MSCs) hold tremendous potential as a targeted cell-based delivery platform for inflammatory and cancer therapy. Genetic manipulation of MSCs, however, is challenging, and therefore, most studies using MSCs as therapeutic cell carriers have utilized viral vectors to transduce the cells. Here, we demonstrate, for the first time, an alternative approach for the efficient transfection of MSCs; therapeutic ultrasound (TUS).

Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction.

Unlabelled: Injectable scaffolds for cardiac tissue regeneration are a promising therapeutic approach for progressive heart failure following myocardial infarction (MI). Their major advantage lies in their delivery modality that is considered minimally invasive due to their direct injection into the myocardium. Biomaterials comprising such scaffolds should mimic the cardiac tissue in terms of composition, structure, mechanical support, and most importantly, bioactivity.

Dynamic Autologous Reendothelialization of Small-Caliber Arterial Extracellular Matrix: A Preclinical Large Animal Study.

Effective cellularization is a key approach to prevent small-caliber (<4 mm) tissue-engineered vascular graft (TEVG) failure and maintain patency and contractility following implantation. To achieve this goal, however, improved biomimicking designs and/or relatively long production times (typically several months) are required. We previously reported on porcine carotid artery decellularization yielding biomechanically stable and cell supportive small-caliber (3-4 mm diameter, 5 cm long) arterial extracellular matrix (scaECM) vascular grafts.

Natural myocardial ECM patch drives cardiac progenitor based restoration even after scarring.

Objective: To evaluate the regenerative capacity of non-supplemented and bioactive patches made of decellularized porcine cardiac extracellular matrix (pcECM) and characterize the biological key factors involved in possible cardiac function (CF) restoration following acute and 8weeks chronic MI.

Background: pcECM is a key natural biomaterial that can affect cardiac regeneration following myocardial infarction (MI), through mechanisms, which are still not clearly understood.

Methods: Wistar rats underwent MI and received pcECM patch (pcECM-P) treatment in either acute or chronic inflammatory phases.

Nanoghosts as a Novel Natural Nonviral Gene Delivery Platform Safely Targeting Multiple Cancers.

Nanoghosts derived from mesenchymal stem cells and retaining their unique surface-associated tumor-targeting capabilities were redesigned as a selective and safe universal nonviral gene-therapy platform. pDNA-loaded nanoghosts efficiently targeted and transfected diverse cancer cells, in vitro and in vivo, in subcutaneous and metastatic orthotopic tumor models, leading to no adverse effects. Nanoghosts loaded with pDNA encoding for a cancer-toxic gene inhibited the growth of metastatic orthotopic lung cancer and subcutaneous prostate cancer models and dramatically prolonged the animals' survival.

PLGA-Listeriolysin O microspheres: Opening the gate for cytosolic delivery of cancer antigens.

Strategies for cancer protein vaccination largely aim to activate the cellular arm of the immune system against cancer cells. This approach, however, is limited since protein vaccines mostly activate the system's humoral arm instead. One way to overcome this problem is to enhance the cross-presentation of such proteins by antigen-presenting cells, which may consequently lead to intense cellular response.