An in vitro tumorigenesis model based on live-cell-generated oxygen and nutrient gradients

The tumor microenvironment (TME) is multi-cellular, spatially heterogenous, and contains cell-generated gradients of soluble molecules. Current cell-based model systems lack this complexity or are difficult to interrogate microscopically. We present a 2D live-cell chamber that approximates the TME and demonstrate that breast cancer cells and macrophages generate hypoxic and nutrient gradients, self-organize, and have spatially varying phenotypes along the gradients, leading to new insights into tumorigenesis.

Dual-responsive biohybrid neutrobots for active target delivery

Swimming biohybrid microsized robots (e.g., bacteria- or sperm-driven microrobots) with self-propelling and navigating capabilities have become an exciting field of research, thanks to their controllable locomotion in hard-to-reach areas of the body for noninvasive drug delivery and treatment. However, current cell-based microrobots are susceptible to immune attack and clearance upon entering the body. Here, we report a neutrophil-based microrobot (“neutrobot”) that can actively deliver cargo to malignant glioma in vivo. The neutrobots are constructed through the phagocytosis of Escherichia coli membrane-enveloped, drug-loaded magnetic nanogels by natural neutrophils, where the E. coli membrane camouflaging enhances the efficiency of phagocytosis and also prevents drug leakage inside the neutrophils. With controllable intravascular movement upon exposure to a rotating magnetic field, the neutrobots could autonomously aggregate in the brain and subsequently cross the blood-brain barrier through the positive chemotactic motion of neutrobots along the gradient of inflammatory factors. The use of such dual-responsive neutrobots for targeted drug delivery substantially inhibits the proliferation of tumor cells compared with traditional drug injection. Inheriting the biological characteristics and functions of natural neutrophils that current artificial microrobots cannot match, the neutrobots developed in this study provide a promising pathway to precision biomedicine in the future.

Cardiac Regeneration: the Heart of the Issue

Purpose of Review The regenerative capacity of the heart is insufficient to compensate for the pathological loss of cardiomyocytes during a large injury, such as a myocardial infarction. Therapeutic options for patients after cardiac infarction are limited: treatment with drugs that only treat the symptoms or extraordinary measures, such as heart transplantation. Cell therapies offer a promising strategy for cardiac regeneration. In this brief review, the major issues in these areas are discussed, and possible directions for future research are indicated. Recent Findings Cardiac regeneration can be obtained by at least two strategies: the first is direct to generate an ex vivo functional myocardial tissue that replaces damaged tissue; the second approach aims to stimulate endogenous mechanisms of cardiac repair. However, current cell therapies are still hampered by poor translation into actual clinical applications. Summary In this scenario, recent advancements in cell biology and biomaterial-based technologies can play a key role to design effective therapeutic approaches.

Adoptive Transfer of Regulatory Immune Cells in Organ Transplantation

Chronic graft rejection remains a significant barrier to solid organ transplantation as a treatment for end-organ failure. Patients receiving organ transplants typically require systemic immunosuppression in the form of pharmacological immunosuppressants for the duration of their lives, leaving these patients vulnerable to opportunistic infections, malignancies, and other use-restricting side-effects. In recent years, a substantial amount of research has focused on the use of cell-based therapies for the induction of graft tolerance. Inducing or adoptively transferring regulatory cell types, including regulatory T cells, myeloid-derived suppressor cells, and IL-10 secreting B cells, has the potential to produce graft-specific tolerance in transplant recipients. Significant progress has been made in the optimization of these cell-based therapeutic strategies as our understanding of their underlying mechanisms increases and new immunoengineering technologies become more widely available. Still, many questions remain to be answered regarding optimal cell types to use, appropriate dosage and timing, and adjuvant therapies. In this review, we summarize what is known about the cellular mechanisms that underly the current cell-based therapies being developed for the prevention of allograft rejection, the different strategies being explored to optimize these therapies, and all of the completed and ongoing clinical trials involving these therapies.

Extended GLRT Detection of Moving Targets for Multichannel SAR Based on Generalized Steering Vector

A generalized likelihood ratio test (GLRT) with the constant false alarm rate (CFAR) property was recently developed for adaptive detection of moving targets in focusing synthetic aperture radar (SAR) images. However, in the multichannel SAR-ground moving-target indication (SAR-GMTI) system, image defocus is inevitable, which will remarkably degrade the performance of the GLRT detector, especially for the lower radar cross-section (RCS) and slower radial velocity moving targets. To address this issue, based on the generalized steering vector (GSV), an extended GLRT detector is proposed and its performance is evaluated by the optimum likelihood ratio test (LRT) in the Neyman-Pearson (NP) criterion. The joint data vector formulated by the current cell and its adjacent cells is used to obtain the GSV, and then the extended GLRT is derived, which coherently integrates signal and accomplishes moving-target detection and parameter estimation. Theoretical analysis and simulated SAR data demonstrate the effectiveness and robustness of the proposed detector in the defocusing SAR images.

From the Basis of Epimorphic Regeneration to Enhanced Regenerative Therapies

Current cell-based therapies to treat degenerative diseases such as osteoarthritis (OA) fail to offer long-term beneficial effects. The therapeutic effects provided by mesenchymal stem cell (MSC) injection, characterized by reduced pain and an improved functional activity in patients with knee OA, are reported at short-term follow-up since the improved outcomes plateau or, even worse, decline several months after MSC administration. This review tackles the limitations of MSC-based therapy for degenerative diseases and highlights the lessons learned from regenerative species to comprehend the coordination of molecular and cellular events critical for complex regeneration processes. We discuss how MSC injection generates a positive cascade of events resulting in a long-lasting systemic immune regulation with limited beneficial effects on tissue regeneration while in regenerative species fine-tuned inflammation is required for progenitor cell proliferation, differentiation, and regeneration. Finally, we stress the direct or indirect involvement of neural crest derived cells (NCC) in most if not all adult regenerative models studied so far. This review underlines the regenerative potential of NCC and the limitations of MSC-based therapy to open new avenues for the treatment of degenerative diseases such as OA.

CAN INDIA EMERGE AS AN ALTERNATE HUB FOR CELL PHONE MANUFACTURING POST COVID 19?

The COVID 19 pandemic outbreak has forced countries worldwide to undergo lockdown which in turn has brought economic stability to a standstill. The disruptions caused in the supply chain due to restriction of flow of material across countries has been a wakeup call for many countries for employing a de-risk manufacturing strategy and look for alternatives other than China by exploring various other promising countries. This research aims to understand the impact of COVID 19 on the global supply chain of cell phone manufacturing industry .The study gives an understanding on post COVID scenario of cell phone manufacturing industry in India considering the de-risk strategies employed by various countries. The research highlights the strengths and weaknesses of the current cell phone manufacturing industry, and also suggests key recommendations on the roadmap to emerge as the new manufacturing hub in near future.

Cell-Based Therapy Manufacturing in Stirred Suspension Bioreactor: Thoughts for cGMP Compliance

Cell-based therapy (CBT) is attracting much attention to treat incurable diseases. In recent years, several clinical trials have been conducted using human pluripotent stem cells (hPSCs), and other potential therapeutic cells. Various private- and government-funded organizations are investing in finding permanent cures for diseases that are difficult or expensive to treat over a lifespan, such as age-related macular degeneration, Parkinson’s disease, or diabetes, etc. Clinical-grade cell manufacturing requiring current good manufacturing practices (cGMP) has therefore become an important issue to make safe and effective CBT products. Current cell production practices are adopted from conventional antibody or protein production in the pharmaceutical industry, wherein cells are used as a vector to produce the desired products. With CBT, however, the “cells are the final products” and sensitive to physico- chemical parameters and storage conditions anywhere between isolation and patient administration. In addition, the manufacturing of cellular products involves multi-stage processing, including cell isolation, genetic modification, PSC derivation, expansion, differentiation, purification, characterization, cryopreservation, etc. Posing a high risk of product contamination, these can be time- and cost- prohibitive due to maintenance of cGMP. The growing demand of CBT needs integrated manufacturing systems that can provide a more simple and cost-effective platform. Here, we discuss the current methods and limitations of CBT, based upon experience with biologics production. We review current cell manufacturing integration, automation and provide an overview of some important considerations and best cGMP practices. Finally, we propose how multi-stage cell processing can be integrated into a single bioreactor, in order to develop streamlined cGMP-compliant cell processing systems.