New Drug Could Improve Effectiveness of Stem Cell Therapy – Pain News Network

By Pat Anson, PNN Editor

Scientists have developed an experimental drug that can lure stem cells to damaged tissues and help them heal -- a discovery being touted as a major advancement in the field of regenerative medicine.

The findings, recently published in the Proceedings of the National Academy of Sciences (PNAS), could improve the effectiveness of stem cell therapy in treating spinal cord injuries, stroke, amyotrophic lateral sclerosis(ALS), Parkinsons disease and other neurodegenerative disorders. It could also expand the use of stem cells to treat conditions such as heart disease and arthritis.

The ability to instruct a stem cell where to go in the body or to a particular region of a given organ is the Holy Grail for regenerative medicine, said lead authorEvan Snyder, MD, director of theCenter for Stem Cells & Regenerative Medicineat Sanford Burnham Prebys Medical Discovery Institute in La Jolla, CA. Now, for the first time ever, we can direct a stem cell to a desired location and focus its therapeutic impact.

Over a decade ago, Snyder and his colleagues discovered that stem cells are drawn to inflammation -- a biological fire alarm that signals tissue damage has occurred. However, using inflammation as a therapeutic lure for stem cells wasnt advisable because they could further inflame diseased or damaged organs, joints and other tissue.

To get around that problem, scientists modified CXCL12 -- an inflammatory molecule that Snyders team discovered could guide stem cells to sites in need of repair to create a drug called SDV1a. The new drug works by enhancing stem cell binding, while minimizing inflammatory signals.

Since inflammation can be dangerous, we modified CXCL12 by stripping away the risky bit and maximizing the good bit, Snyder explained. Now we have a drug that draws stem cells to a region of pathology, but without creating or worsening unwanted inflammation.

To demonstrate its effectiveness, Snyders team injected SDV1a and human neural stem cells into the brains of mice with a neurodegenerative disease called Sandhoff disease. The experiment showed that the drug helped stem cells migrate and perform healing functions, which included extending lifespan, delaying symptom onset, and preserving motor function for much longer than mice that didnt receive the drug. Importantly, the stem cells also did not worsen the inflammation.

Researchers are now testing SDV1as ability to improve stem cell therapy in a mouse model of ALS, also known as Lou Gehrigs disease, which is caused by a progressive loss of motor neurons in the brain. Previous studies conducted by Snyders team found that broadening the spread of neural stem cells helps more motor neurons survive so they are hopeful that SDV1a will improve the effectiveness of neuroprotective stem cells and help slow the onset and progression of ALS.

We are optimistic that this drugs mechanism of action may potentially benefit a variety of neurodegenerative disorders, as well as non-neurological conditions such as heart disease, arthritis and even brain cancer, says Snyder. Interestingly, because CXCL12 and its receptor are implicated in the cytokine storm that characterizes severe COVID-19, some of our insights into how to selectively inhibit inflammation without suppressing other normal processes may be useful in that arena as well.

Snyders research is supported by the National Institutes of Health, U.S. Department of Defense, National Tay-Sachs & Allied Disease Foundation, Childrens Neurobiological Solutions Foundation, and the California Institute for Regenerative Medicine (CIRM).

Thanks to decades of investment in stem cell science, we are making tremendous progress in our understanding of how these cells work and how they can be harnessed to help reverse injury or disease, says Maria Millan, MD, president and CEO of CIRM. This drug could help speed the development of stem cell treatments for spinal cord injury, Alzheimers, heart disease and many other conditions for which no effective treatment exists.

Originally posted here:
New Drug Could Improve Effectiveness of Stem Cell Therapy - Pain News Network

Are stable producer cells the future of viral vector manufacturing and when will allogeneic cell therapy take hold? – BioPharma-Reporter.com

The publication, based on data generated from a questionnaire with 150 industry representatives, explores the challenges and solutions facing cell and gene therapy (CGT) companies over the next few years.

The top six trends identified in the CRB survey were:

We got the inside track from Noel Maestre, director of SlateXpace, a CRB solution focused on suite-based manufacturing platforms for the Advanced Therapy Medicinal Products (ATMP) and Peter Walters, CRBs director of ATMP, on how the CGT landscape is likely to develop in the short-term.

In a recent report, the MITs Center for Biomedical Innovationprojected that around 500,000 patients will have been treated with 40-60 approved gene therapies by 2030.

Going from the current scenario whereby only a few gene therapies are approved to 60 launches in a decade would represent an extraordinary leap forward and would dramatically change how medicine is actually perceived, said Maestre.

But as regards CGT production today, especially autologous cell therapy (ACT) work, he said that while the science exists the technology - process equipment, facility design and automation platforms - is really still trying to catch up, endeavoring to address a sector that has exploded in the past five years, he commented.

Looking ahead at the CGT landscape over the next few years, he expects a significant amount of change. The science is evolving we see the industry moving away from old cell lines to new cell lines or moving away from viral vectors altogether and using cleavage enzymes as a gene editing tool.

A new host cell line stable producer lines is gaining momentum, he said.

We are seeing the industry moving towards suspension cell culture from less than optimal cell lines, and then further going into producer cell lines.

A full 65% of respondents to the CRB poll said they are developing or intend to develop this type of vector host cell, drawn by the potential for a less expensive, more scalable process.

CRB: Our survey findings provide a data-driven snapshot of an industry whose intellectual capital and cutting-edge science is too often betrayed by outdated technology and applications ill-suited for commercial scale at a time when demand for urgent therapies is rising.

Once the industry gets to the point where producer cell lines are more like a name brand, easier to pull off the shelf and use, it will be a much more cost-effective way to produce viral vectors.

But we are right on the cusp - a lot of companies are recognizing the opportunity and are investing the time and money into producing these. And we also see a lot of contract development and manufacturing organizations (CDMOs) producing their own cell lines in house and using those as a lure to [attract the clinical material work] of their clients, said Walters.

According to Maestre, and the CRB survey data backs him up, the product pipelines of companies operating in the CGT space are going to get more complex, for the next five years at least.

More than half of those polled indicated they expect to adopt a multimodal solution within the next two years, with flexibility, scalability, operational efficiency, and speed to market as the top drivers.

Every company is going to be dealing with this dilemma of whether they build dedicated spaces for each of their different modalities, or whether they build highly flexible facilities that can allow them to accommodate whatever is coming next, said Maestre.

He also sees a lot more companies wanting to integrate their supply chain, bringing a lot of manufacturing in-house whereas before they would have been reliant on a whole set of different CDMOs and manufacturers.

Project delivery is also where change is occurring.

We are seeing the industry really moving away from the way projects were executed in the past into a much more integrated model; they are looking for turnkey facility delivery and they want turnaround to be faster. COVID-19 has only accentuated that, with project timelines compressed by 30-40%, and I dont think that it is ever going back to the way it was I think that is going to become the standard, commented Maestre.

And another major trend over the next few years will be around the cost of therapies. As they become more commonplace and there are more and more CGT licensed products, the costs will come down.

Projecting forward, Walters sees an eventual shift away from autologous to allogeneic cell therapy.

As the technology continues to develop and the science continues to improve and new and better ways are found to use and leverage cells, we will see companies moving to a scalable allogeneic model, getting away from having to do that point-of-care, personalized tracking and more towards a classic manufacturing model that allows them to produce cells in advance in a way that they can be scaled up.

The idea, evidently, is to process cells for not one but dozens of patients at a time.

We see the industry moving towards donated cells for allogeneic therapy and we are also seeing the beginnings of a shift to using stem cells that can be genetically modified and scaled up and differentiated to become T-Cells or NK cells. I dont think industry has settled on a course yet but there are a lot of companies trying to find that pathway, trying to find the edge to move their manufacturing platform that way, remarked Walters.

Right now, though, all facets of CGT manufacturing are under pressure from COVID-19 vaccine production, they said.

There is significant shortage of cleanroom manufacturing space to manufacture and develop the almost 1,200 CGT products in clinical trials currently.

What we are seeing is that CDMOs have so much demand - they have 12-18 months of backlog in terms of contracts for product development so they are building [new facilities] very rapidly.

As owner operator companies are stuck with that delay in getting their products into development, they are also developing a significant amount of manufacturing space on their own. But while both branches are building as fast as they can, it still isnt enough.

We are constantly hearing from our clients that they are concerned about their supply chains and being able to secure their material. Right now, a lot of companies are moving towards a combination of using CDMOs and manufacturing in-house, said Maestre.

CRB is a provider of engineering, architecture, construction and consulting solutions to the global life sciences and advanced technology industries, with over 1,300 employees.

Here is the original post:
Are stable producer cells the future of viral vector manufacturing and when will allogeneic cell therapy take hold? - BioPharma-Reporter.com

How Stem Cell Therapy Market Will Dominate In Coming Years? Report Covering Products, Financial Information, Developments, Swot Analysis And…

The Global Stem Cell Therapy Market analysis report published on IndustryGrowthInsights.com is a detailed study of market size, share and dynamics covered in XX pages and is an illustrative sample demonstrating market trends. This is a latest report, covering the current COVID-19 impact on the market. The pandemic of Coronavirus (COVID-19) has affected every aspect of life globally. This has brought along several changes in market conditions. The rapidly changing market scenario and initial and future assessment of the impact is covered in the report. It covers the entire market with an in-depth study on revenue growth and profitability. The report also delivers on key players along with strategic standpoint pertaining to price and promotion.

Get FREE Exclusive PDF Sample Copy of This Report: https://industrygrowthinsights.com/request-sample/?reportId=168110

The Global Stem Cell Therapy Market report entails a comprehensive database on future market estimation based on historical data analysis. It enables the clients with quantified data for current market perusal. It is a professional and a detailed report focusing on primary and secondary drivers, market share, leading segments and regional analysis. Listed out are key players, major collaborations, merger & acquisitions along with upcoming and trending innovation. Business policies are reviewed from the techno-commercial perspective demonstrating better results. The report contains granular information & analysis pertaining to the Global Stem Cell Therapy Market size, share, growth, trends, segment and forecasts from 2020-2026.

With an all-round approach for data accumulation, the market scenarios comprise major players, cost and pricing operating in the specific geography/ies. Statistical surveying used are SWOT analysis, PESTLE analysis, predictive analysis, and real-time analytics. Graphs are clearly used to support the data format for clear understanding of facts and figures.

Customize Report and Inquiry for The Stem Cell Therapy Market Report: https://industrygrowthinsights.com/enquiry-before-buying/?reportId=168110

Get in touch with our sales team, who will guarantee you to get a report that suits your necessities.

Primary research, interviews, news sources and information booths have made the report precise having valuable data. Secondary research techniques add more in clear and concise understanding with regards to placing of data in the report.

The report segments the Global Stem Cell Therapy Market as: Global Stem Cell Therapy Market Size & Share, by Regions

Global Stem Cell Therapy Market Size & Share, by Products Autologous Allogeneic Stem Cell Therap

Global Stem Cell Therapy Market Size & Share, Applications Musculoskeletal Disorder Wounds & Injuries Cornea Cardiovascular Diseases Others

Key Players Osiris Therapeutics NuVasive Chiesi Pharmaceuticals JCR Pharmaceutical Pharmicell Medi-post Anterogen Molmed Takeda (TiGenix) Stem Cell Therap

Avail the Discount on this Report @ https://industrygrowthinsights.com/ask-for-discount/?reportId=168110

IndustryGrowthInsights offers attractive discounts on customization of reports as per your need. This report can be personalized to meet your requirements. Get in touch with our sales team, who will guarantee you to get a report that suits your necessities.

About IndustryGrowthInsights: INDUSTRYGROWTHINSIGHTS has set its benchmark in the market research industry by providing syndicated and customized research report to the clients. The database of the company is updated on a daily basis to prompt the clients with the latest trends and in-depth analysis of the industry. Our pool of database contains various industry verticals that include: IT & Telecom, Food Beverage, Automotive, Healthcare, Chemicals and Energy, Consumer foods, Food and beverages, and many more. Each and every report goes through the proper research methodology, validated from the professionals and analysts to ensure the eminent quality reports.

Contact Info: Name: Alex Mathews Address: 500 East E Street, Ontario, CA 91764, United States. Phone No: USA: +1 909 545 6473 Email: [emailprotected] Website: https://IndustryGrowthInsights.com

See more here:
How Stem Cell Therapy Market Will Dominate In Coming Years? Report Covering Products, Financial Information, Developments, Swot Analysis And...

The Promise of Using Cell Cultures To Fight SARS-CoV-2 – Technology Networks

Read Time:

The COVID-19 pandemic has significantly disrupted scientific activities. Labs have been forced to shut down. Researchers have been placed on furloughs and advised to work from home. Animal facilities have also been scaled down and shipping of research supplies has been delayed. However, despite these challenges, many researchers remain undeterred and are applying their scientific expertise in the fight against SARS-CoV-2, the coronavirus responsible for COVID-19. Portable diagnostic kits with short turnaround time have been invented to facilitate timely and on-field viral detection. Masks made of different materials have been tested for their ability to prevent aerosol transmission and re-usable masks that can be disinfected with electrical fields/heat have been commercialized. Furthermore, the pandemic has significantly accelerated vaccine development and in an unprecedented case, motivated companies with competing interests to work together in efforts to address this global health crisis. In order to fully win the fight against SARS-CoV-2, it is paramount to understand the biological mechanisms of COVID-19 viral infection. A variety of models have been used, but none as frequently as cell culture. Cell cultures, including immortalized cell lines, stem cell lines and primary cells from patients, are being used as in vitro models to understand viral entry into human cells. They are useful for drug screening purposes and as cellular factories to generate viral particles for testing. This article highlights the promising research being conducted using cell cultures and illustrates how these models are contributing to the fight against COVID-19. Cell cultures A variety of in vitro cell cultures exist and depending on the purpose of the experiments, they each have their pros and cons. Immortalized cell lines The most common cell cultures are immortalized cell lines, such as HeLa, CHO and Vero cells. As the name suggests, these are cells that either by natural mutation or genetic engineering, have become immortal, enabling them to be grown in culture indefinitely. These cells divide at a relatively fast rate, are cheaper to obtain and maintain, and are generally more homogenous in their biological properties. Cell lines are most suitable for use when there is a demand for high cell numbers such as in an initial phase of high-throughput COVID-19 drug screening to identify a target. Stem cell lines Stem cell lines, such as mesenchymal and induced pluripotent stem cells (iPSCs), on the other hand, have the inherent ability to proliferate indefinitely, provided that they receive the appropriate growth signals. Stem cells can either be obtained directly from their sources or have been treated with a de-differentiation chemical cocktail to revert them to a stem-like state. As they bear more similar biological characteristics to cells in vivo, they are better models for biological testing. However, primary stem cells can be difficult and expensive to maintain. For instance, some primary stem cells require feeder cells to maintain their stemness and most can only grow on surfaces coated with specific biomaterials. In cases where patientscells are not easily obtainable, iPSCs can also be differentiated to diverse lineages including neurons, cardiomyocytes, and immune cells for applications like COVID-19 drug testing to investigate potential adverse effects of drugs. iPSCs have also been used to construct 3D cell cultures known as organoids to facilitate biological investigations in a 3D environment in efforts to more closely recapitulate the in vivo setting. Primary cells The final type of cell cultures are primary cells from patients. It remains extremely challenging to grow these cells because commercially available products like media are not optimized for them, and thus these cells do not proliferate well ex vivo. Thus far, the exception may be primary leukocytes from patients which can be cultured efficiently ex vivo. This is also partly driven by developments in Chimeric Antigen Receptor (CAR) T-cell therapy to manufacture engineered T cells for cancer immunotherapy. Ex vivo culture of primary immune cells has been particularly useful to study the immune repertoire involved in antigen recognition and antibody production against SARS-CoV-2. Cell culture for understanding disease One of the most important questions regarding COVID-19 is the mechanism of viral entry into host cells. Cell culture has been an invaluable tool for discovering the role of the human angiotensin-converting enzyme 2 (hACE2) cell surface receptor in facilitating viral entry into human cells. Shang and colleagues at the University of Minnesota made use of a variety of immortalized cell lines (HEK293T, HeLa, Calu-3 and MRC-5) and found that a viral surface spike protein binds to hACE2 through its receptor-binding domain (RBD) and is proteolytically activated by human host proteases. The coronavirus membrane fusion S2 protein was also discovered as an essential protein for viruscell membrane fusion. This study suggests that antibody-based therapeutics with high affinity to hACE2 or RBD could inhibit SARS-CoV-2 from associating with the host cell, therefore preventing its entry. Finally, compounds that can inhibit host cell membrane and lysosomal proteases responsible for activating viral entry, may also be useful as therapeutics. These findings were also supported by a subsequent study by Dr Markus Hoffman and colleagues which showed that an inhibitor for the serine protease TMPRSS2 (a cell surface protein) was able to block SARS-CoV-2 infection in lung cells. We identified the cellular protein TMPRSS2 as a crucial factor for SARS-CoV-2 infection and showed that an existing drug that is approved in Japan for treatment of pancreatitis, camostat mesylate, can inhibit TMPRSS2 activity and thus block SARS-CoV-2 infection in cell culture experiments, said Hoffman. Hoffman added that we are currently exploring the antiviral effects of camostat mesylate and related drugs in culture systems that represent the human respiratory tract, and we are collecting data on the required dosage and longevity of the drugs. Finally, we are planning to do efficacy testing of the most promising drugs in non-human primates that have been experimentally infected with SARS-CoV-2. Studies using cell cultures have also provided insights into symptoms of COVID-19 infection. To understand why COVID-19-positive patients suffer from a persistent cough and other respiratory effects, Jia and colleagues analyzed ACE2 receptor expression in cell cultures of primary human airway epithelia, and found high receptor expression in these airway cells, as well as a correlation between ACE2 expression and susceptibility to SARS-CoV-2 infection. Researchers have also identified high ACE2 expression on human neurons, particularly the olfactory neuronal cells, possibly explaining the loss of smell experienced in some patients. Recently, a greater ratio of ACE2 positive cells were found to be present in the digestive tract compared to the lungs, and the receptor expression was higher in gastric cancer cells, potentially explaining the symptom of diarrhea. This myriad of COVID-19 related symptoms has motivated the search for cellular tropism by SARS-CoV-2. For instance, Chu and colleagues systematically investigated the replication rate and cellular damage due to SARS-CoV-2 in cells from different species (humans, non-human primates, cats, rabbits, and pigs) and organs. Their study revealed the range of cells that SARS-CoV-2 is able to infect efficiently for generating physiologically relevant animal models for studying the disease. To better generate policies for managing the spread of SARS-CoV-2, scientists also made use of cell cultures to understand the possible routes of virus entry into the body. For instance, Xu and co-workers made use of a bulk RNA sequencing technique and found that ACE2 was highly expressed on the mucosa of the oral cavity, especially in epithelial cells on tongue tissue derived from patients. This finding suggests that the oral cavity is a susceptible route for SARS-CoV-2 entry, in addition to the lungs. Cell culture for drug screening Cell cultures are invaluable tools for high-throughput drug screening to identify therapeutics capable of inhibiting entry and replication of SARS-CoV-2. Touret and colleagues screened 1,520 US Food and Drug Administration (FDA)-approved drugs in vitro for their anti-viral properties using VeroE6 and Caco-2 immortalized cell lines. From this study, they identified 90 compounds spanning different drug categories such as antibiotics and proton pump inhibitors, that may be therapeutically relevant. Similarly, Ianevski and co-workers made use of VeroE6 cell lines and found that a combination of orally-available virus-directed nelfinavir and host-directed amaodiaquine exhibited the best therapeutic effects against SARS-CoV-2 across 136 broad spectrum antiviral products. Recently, Daniloski and colleagues also performed a knock-out screening of genes in the human genome to identify which are needed for SARS-CoV-2 infection of human alveolar epithelial cell lines. They discovered that the most important genes included those encoding the vacuolar ATPase proton pump and Arp2/3 complex which they also validated using RNA interference knock-out and small molecule inhibitors. Going a step further, by using both in vitro cell culture and computational analysis approaches, Prof. Tudor Oprea and his team screened almost 4,000 approved drugs and identified those with structural similarity to hydroxychloroquine. In their study, they discovered that zuclopenthixol and nebivolol blocked COVID-19 infection at a low concentration with minimal side effects, and proposed that these drugs may be further tested for their therapeutic value. Critical to our work was not just the computer-guided effort, but also the dual (independent) experimental confirmation of these drugs in vitro. Experiments conducted first at University of New Mexico Health Sciences Center (Steven Bradfute lab) were later confirmed at the University of Tennessee Health Sciences Center (Colleen Jonsson lab), said Oprea. Given the documented cases of reinfection, it is possible that vaccines may not work against SARS-CoV-2, so we need to keep pursuing effective therapeutic approaches. Combining drugs with synergistic effects may be the best way to go forward. The thought behind this is to give a lower dose of each drug which can be safer and accessible because some drugs are in shortages. At the same time, this approach delivers a two-pronged attack against virus which is prone to develop drug resistance when subjected to monotherapy, Oprea added. Cell culture for producing viral particles To study SARS-CoV-2 transmission and infection, such as testing how different mask materials block transmission of SARS-CoV-2, it is necessary to obtain samples of the virus. Attributing to their lower costs of maintenance and fast cell division, immortalized cell lines have been used as factories to generate viral particles. This facilitates high-throughput production of viruses for testing and greatly enhances scientific study when it is challenging to access patients samples for extracting viruses. Kaye and co-workers showed that viral replication of severe acute respiratory syndromeassociated coronavirus (SARS-CoV) occurs efficiently in different cell lines. The viruses could then be isolated at high titers in the absence of specific cytopathic effects. Similar technology can likely be applied to SARS-CoV-2 as it belongs to the same virus family. Conclusion Cell cultures have facilitated studies investigating the biology of SARS-CoV-2 infection and have been harnessed for drug screening, they are also useful as a means for producing viral particles and therapeutics. Cell cultures have been an invaluable tool for biological studies and will be a key contributor in the ongoing fight against COVID-19.

Continued here:
The Promise of Using Cell Cultures To Fight SARS-CoV-2 - Technology Networks