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Cell Therapy for COVID-19
Technology for Fighting COVID-19
Other Resources
Model (cell/organoid/animal) for COVID-19
Resource ID#: 188
Description:
The Wake Forest Institute for Regenerative Medicine has developed a “body on a chip” platform that has demonstrated exceptional performance in modeling normal and pathological human physiology. The platform includes a perfused microfluidic system connecting a series of tissue chambers, each housing a different microengineered organ/tissue equivalent (OTE). Solid organs are represented as 3D spherical structures, while the lung construct is arranged in a pseudostratified architecture and includes an epithelial air interface with underlying interstitium and endothelial fluid interface. Production of mucus and surfactant provides a physiologically relevant mechanical barrier, a critical factor for modeling viral infectivity in a realistic manner. Additionally, the lung OTE epithelial cells become ciliated to a degree equivalent to that of native lung. This is important, as it dramatically increases the surface area to which virus may attach. These phenotypic characteristics increase the fidelity of the OTE for modeling viral infection kinetics. The presence of immune cells and fibroblasts in the interstitium also allows for modeling of inflammation and subsequent fibrosis, respectively. ACE-2 receptor, the port of cellular entry for SARS-CoV-2, has been demonstrated on the epithelial cells of the lung OTE at levels similar to those seen in native lung. Preliminary studies show that SARS-CoV-2 is able to infect these lung OTE constructs and that the infection propagates and spreads within the system. One of the major benefits of this model is the ability to include downstream OTEs in the microfluidic circuit. For SARS-CoV-2 infections this is critical, as many tissue types including liver, cardiac, and vasculature have been implicated in the overall pathology of COVID-19. Because these constructs are engineered from populations of donor derived human cells, the role of specific cell types in the disease process may be modeled. For instance, epithelial cells from an elderly donor may be matched with macrophages from a younger donor, and vice versa. This opens the potential for conducting studies for uncovering the mechanism that drive many of the unique epidemiological characteristics that have been observed in COVID-19.
Resource ID#: 192
Description:
Allevi is using its state-of-the-art 3D bioprinting platform to fabricate SARS-CoV-2-infected, human airway and lung organoid models. These models are being used to study COVID-19 disease progression and for rapid drug screening.
Allevi's commercially available 3D bioprinters enable automated biofabrication of a variety of tissue types.
Resource ID#: 193
Description:
Human Organ-on-a-chip in vitro culture devices can be used to model human lung airway epithelium microenvironment to study SAR-Cov-2 (COVID-19) diseases pathogenesis such as virus entry, replication, strain-dependent virulence, host cytokine production, and recruitment of circulating immune cells in response to infection, as well as to study the effect of existing and novel therapeutics on the infected epithelium. The human Airway Chips have provided a more stringent and physiologically relevant platform to assess inhibitory activities of several clinically approved drugs under dynamic flow condition to expedite drug repurposing for considerations in future clinical testing reported in the two following publications.
https://www.biorxiv.org/content/10.1101/2020.04.13.039917v3
https://www.biorxiv.org/content/10.1101/2020.04.13.039917v2.article-metrics
The Organ-on-Chip technology was initially developed at the Wyss Institute, Harvard University, and is now commercially available through Emulatebio company.
Resource ID#: 199
Description:
PepGel LLC has developed 3D model systems mimicking extracellular matrix that produces high content physiologically formed stem cell spheroids or tumor spheroids or organoids (~2x104 spheroids/mL) with high representation of in vivo like information at gene and RNA levels with 15-25 proliferation doublings and viability of 85-95%. Importantly, these spheroids can be easily harvested from the 3D model and then can also be re-encapsulated in PGmatrix for further downstream applications such as differentiation into various somatic cells (i.e., hepatocytes or cardiomyocytes). PGmatrix-Spheroids system is designed to mimic the natural extracellular matrix (ECM), a 3D network matrix composed of fibrous matrix that provides structural integrity for cell survival, with a system that can be handled at room conditions and physiological conditions. PGmatrix-Spheroid system is an advanced 3D model for effective and high predictive development in drug discoveries, disease modeling, cell therapies and regenerative medicine arena, particularly for fighting for the COVID-19. For more information, visit www.pepgel.com or email to info@pepgel.com,
Resource ID#: 201
Description:
The Wake Forest Institute for Regenerative Medicine has an established 3D bioprinting platform that fabricates complex and composite three-dimensional free-form tissue constructs. This platform was initially developed to produce clinically relevant size tissue constructs to replace injured or missing tissues to achieve long-term function through proper vascularization at the micro- and macro-scale. We have established a strong foundation for complex cellular printing and precise tissue patterning using optimized tissue-specific bioink formulations with materials derived from natural to synthetic sources. The composite tissue printing platform generates multi-cellular constructs with tissue and organ-specific functions. This bioprinting platform would be ideal for producing in vitro tissue and organ models for testing the effects of COVID-19 infections, which would allow for an enhanced understanding of the pathogenesis and tissue responses. More importantly, the life-sized infected tissue models could be used to test the effects of various therapeutic agents and evaluate the tissue responses. This platform allows for printing different human cells to generate tissues and organ models of target populations, including age, gender, and race. This platform opens numerous possibilities to understand the pathophysiology of COVID-19 better and develop therapeutic modalities at the tissue and organ levels.
Resource ID#: 202
Description:
Coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is defined by respiratory symptoms, but cardiac complications including viral myocarditis are also prevalent. Although ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well understood. Here, we utilize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and RNA sequencing demonstrate that SARS-CoV-2 can enter hiPSC-CMs via ACE2. Viral replication and cytopathic effect induce hiPSC-CM apoptosis and cessation of beating after 72 h of infection. SARS-CoV-2 infection activates innate immune response and antiviral clearance gene pathways, while inhibiting metabolic pathways and suppressing ACE2 expression. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating infection mechanisms and potentially a cardiac-specific antiviral drug screening platform.
Resource ID#: 205
Description:
COVID-19 was rapidly declared a pandemic by the World Health Organization, only three months after the initial outbreak in Wuhan, China. Early clinical care mainly focused on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are also emerging. To determine whether SARS-CoV-2 could target the human brain, we infected iPSC-derived human brain organoids. Our findings show that SARS-CoV-2 was able to infect and kill neural cells, including cortical neurons. This phenotype was accompanied by impaired synaptogenesis. Finally, Sofosbuvir, an FDA-approved antiviral drug, was able to rescue these alterations. Given that there are currently no vaccine or antiviral treatments available, urgent therapies are needed. Our findings put Sofosbuvir forward as a potential treatment to alleviate COVID-19-related neurological symptoms.
Cell Therapy for COVID-19
Resource ID#: 191
Description:
Existing Approved Clinical Trial about to begin recruitment for management/treatment of post-COVID-19 lung damage.
Citation: Alexander, Robert W., (2020) Overview of COVID-19 Lung Damage Clinical Trial Using Cellular Stromal Vascular Fraction (cSVF) and Functional Respiratory Imaging (FRI): Analysis of Pulmonary Injury & Post-Viral (SARS-CoV)-2 Adult Respiratory Distress Syndrome (ARDS). Stem Cell Res. 1(1): 1-19.
Resource ID#: 206
Description:
We are working on several different cell therapy strategies to address safety and efficacy in the treatment of COVID-19.
Technology for Fighting COVID-19
Resource ID#: 187
Description:
Our Xvivo System is a next generation isolator that can provide physiologically relevant gas levels and temperatures for cell incubation as well as cell handling. Available for cGMP-compliant aseptic cell production, the modular Xvivo System is rapidly deployable and already in use for generating human cells for COVID-19 clinical trials.
https://biospherixmedical.com/next-generation-isolator/
We also design and build equipment for researchers looking to provide physiologically relevant conditions to cells in their labs for better scientific reproducibility and faster translatability. The world is waiting for new answers to this global pandemic. We can help you find them. Check out our laboratory equipment here: https://www.biospherix.com/covid-19
Resource ID#: 189
Description:
Bioreactors:
https://www.gembio.com/scinus-bioreactor
https://www.gembio.com/petakar-g3-cassettes
Resource ID#: 191
Description:
Orbital Transports, Inc. has developed a solution for performing cellular and molecular research on CubeSats, and returning the research materials to the scientists. This enables new opportunities for space-based research that can be conducted without human intervention, and thus free scientists from crew time and other limitations inherent to the International Space Station. Also, polar orbits are particularly useful for research requiring exposure to space radiation, and these are not accessible via the International Space Station.
Additional information: https://catalog.orbitaltransports.com/bio-payload-experiment/
Resource ID#: 203
Description:
Title: Mesenchymal Stem/Stromal Cells for COVID-19 Cell Therapy Development
Mesenchymal stem/stromal cells (MSCs) are emerging as a potential treatment modality for COVID-191-3. MSCs have immunomodulatory properties that can be used to combat the inflammatory response caused by the SARS-CoV-2 coronavirus, and the United States Food and Drug Administration (FDA) has granted accelerated approvals to several MSC-based clinical trials for COVID-19. Currently, there are 58 “active” (i.e., Expanded Access: Available; Recruiting; Active, not recruiting; Enrolling by invitation) MSC-based trials for COVID-19. Two of these trials have already reached late stage development (Phase 3) indicating that MSCs have the potential to serve as a powerful therapeutic for combating the effects of COIVD-19.
OrganaBio manufactures off-the-shelf research grade MSCs for allogeneic cell therapy development and is building cGMP manufacturing capabilities, with a forecasted launch in Q3 2021. OrganaBio MSCs are derived from full-term placenta and umbilical cord tissue obtained from consented, non-compensated donors under IRB approved protocols.
For ordering and more information visit www.organabio.com/products
Resource ID#: 204
Description:
Title: Readily Accessibly Cleanrooms for Clinical Trial Manufacturing of COVID-19 Therapies
With so many companies participating in the race to produce a vaccine for COVID-19, the demand for cGMP manufacturing capabilities is rapidly increasing. CDMOs will be able to meet some of this demand, but as availability dwindles there will be a need for alternative GMP manufacturing solutions.
OrganaBio is building a cGMP facility in Miami, FL to manufacture the company’s cellular raw materials for therapeutics development. The facility, which is scheduled to open in Q3 2021, has enough space to accommodate additional ISO 7 cleanrooms that can be reserved by third parties looking for readily accessible GMP manufacturing capabilities. Moreover, OrganaBio can also offer the support services to rapidly manufacture clinical materials. This new paradigm in cGMP manufacturing affords companies flexibility and agility, significantly reducing manufacturing costs and timelines.
For more information visit www.organabio.com/manufacturing
Resource ID#: 207
Description:
3DHistech Digital Pathology Solutions
3DHistech Digital Pathology Solutions, distributed by Epredia, offer a wide variety of whole slide digital imaging scanners, tissue microarrayers and software solutions, that can assist with the research of Sars-CoV-2 infection samples. Advanced quantification software modules, in conjunction with brightfield or fluorescent scanners can also be used to characterize cells and organoids being used in the research of therapeutic applications. All 3DHISTECH whole slide scanners and tissue micorarrayers are research use only in the United States.
Resource ID#: 208
Description:
Arcos and Arcos SL Sample Management Systems
The Arcos tissue block and Arcos SL slide management systems from Epredia, are designed to automate the archiving and retrieval workflow. Using a unique scanner, PDA and barcoded tray components, Arcos and Arcos SL enable researchers assisting in fighting the COVID-19 pandemic a more efficient and accountable management process for critical samples.
Resource ID#: 209
Description:
The Revos Tissue Processor from Epredia enables labs to quickly achieve high-quality tissue processing which protects the genetic material needed while testing and validating organoid models used in the analysis of COVID-19. Less stress on the tissue’s molecular content may lead to more robust research results.
Other Resources
Resource ID#: 198
Description:
Through its hybrid model bringing the best of the CMO and DIY worlds together we offer flexible services and facilities to therapy developers. Our 2,100m2 cleanroom facility offers 6 GMP-ready cleanrooms (4 class C and 2 class B) which can be rented on a flexible basis. We believe such flexibility can be extremely useful for companies looking to scale up/scale out quickly without making large CAPEX investment in a time of uncertainty that is still part of the COVID-19 epidemic.
