Creating innovative tools and high-tech systems for life science researchers around the globe has turned up some fascinating new companies in the last few years; and with Europe currently housing over 35% of biotechnology companies worldwide, we can expect some enticing new discoveries to come. Sweden is certainly not lagging behind, with a buoyant environment for university researchers and students, as well as being known as one of the so-called ideal places to hatch startups, one company is quickly breaking new ground. Founded in 2012 as a spin-off from Chalmers University of Technology, Fluicell is a publicly-traded biotech company providing platforms to investigate cell behavior like never before. Using open-volume microfluidics, they wanr to revolutionize how cells are bioprinted.

Fluicell CEO Victoire Viannay

As a further development to their existing product portfolio, the company has developed a unique high-resolution bioprinting technology in both 2D and 3D called Biopixlar, capable of creating complex tissue-like structures where positioning of individual cells can be controlled from a gamepad, just like you would a videogame. Their original approach is part of a more market-oriented strategy, which brings revolutionary technology straight to the fingertips of users. To get a better sense of what the company is trying to accomplish, 3DPrint.com spoke to Victoire Viannay, Fluicells CEO since 2017.

Since microfluidics is so complex we are trying to create very easy to use platforms for our clients in the life sciences. Our original idea with the Biopixlar was: how to make the system easy to use and fun? So now you can see that we have even incorporated the gamepad, which is a way of creating an easy to use interface, said Viannay.

Biopixlar uses microfluidics which allows for better control of the material at a micro level due to the precision of a pump or microfluidic tube when it comes to directing the flow of biomaterial to actual printing execution. Having such a precise control at the microlevel, systems naturally scale up to the macrolevel and result in high-resolution prints. Additionally, the technology allows the creation of multi-material prints for bioprinting purposes, with users being able to create the materials within the printer technology itself, avoiding the need for laboratory fabrication of the material. A microfluidic chamber can control the mixing of various materials in house. Resulting in a 3D printed structure that is immediately complete without having to deal with gels or scaffolds.

We want to be as true as possible to the science, so it is important for us to protect the landscape, and for that we have a good internal team for harnessing and developing knowledge, knowing that we need to have both invention and method patents.

Fluicell currently has three products on the market, and are now looking actively for partners for the Biopixlar in both Europe and the United States. The research tools Biopen and Dynaflow, allow researchers to investigate the effects of drugs on individual cells at a unique level of detail, as part of their mission to redefine the approach to cell biology, and drug discovery by providing miniaturized instrumentation for single-cell investigations. The company holds a strong IP and patent position with four approved patents in the estate.

Since 2012, the company has moved from Chalmers and established their own laboratories just a few minutes away from the campus, in Gothenburg. There they have commercialized a product portfolio to study single cells, (primarily in the field of drug development), gone public, and launched Biopixlar. Funded by Almi Invest, a local early-stage investor, their aim now is to keep providing innovative tools redefining approaches within cell biology, bioprinting, and secondary drug screening and discovery.

When the company was created we started at Chalmers, but at some point we thought we had to become more independent from the university, so we came up with our own facilities and discovery team, people who work on tissue and disease models in house so that we can do primary research ourselves and the discovery aspects as a way of helping potential clients discover applications which could benefit their needs. We have this both as a demonstration, and also as a contract research organization (CRO) service.

With 20 employees, the company is looking to become the next Swedish bioprinting success, after another company born out of the same city as Fluicell, began selling their popular bioprinters and bioinks, thats Erik Gatenholms CELLINK, now a global big player in biotech. Actually, Viannay claims that Sweden is a great country to start a company, just behind the captivating and successful landscape in the United States.

Sweden is very supportive of new companies. The whole country is built upon innovation, proving that its people were never afraid to try out new things, so it should be the same with bioprinting. Right now there is a very good landscape to work on our projects and i really think that Sweden is ready to support more bioprinting initiatives, suggested Viannay, who is originally French and moved to Sweden after meeting her husband. She has proved to be a great match for the company because of her strong background in law. With a PhD in the field from the Universit Paris II Panthon/Assas and over more than 10 years of experience in labor laws, human resources and legal management, particularly in the field of scientific research, her incorporation came in at just the right time. Her knowledge came in handy during the companys IPO in early 2018.

Two lab experts at Fluicell using the gamepad to control the Biopixlar system

Fluicell has a good growth model based on market penetration, acquiring new geographic areas and expansion and market diversification. So it has worked very well for us while growing the company, next we would be interested in being a profitable company that is very well recognized in the world thanks to our products, which began with the Biopen, and had great traction among our customers. For our Biopixlar technology we would like to further target other areas, such as regenerative medicine, moving towards building tissues and taking it outside of pure research and development by using it to develop something that can go into regenerative or therapeutic medicine.

Join the discussion of this and other 3D printing topics at3DPrintBoard.com.

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Fluicell is Preparing to be the Next Big Player in Swedens Bioprinting Field - 3DPrint.com

The organs-on-chips market is expected to reach USD 45.6 million by 2026 from USD 9.6 million in 2017, at a CAGR of +37%.

OOC (organ-on-a-chip) is a multichannel 3D microfluidic cell culture chip that simulates the activity, dynamics and physiological responses of the entire organ and organ system, a type of artificial organ. It constitutes the subject of more precise biomedical engineering research in the biomedical field. Convergence of laboratory-on-chip (LOC) and cell biology has introduced a new model of in vitro multicellular human organisms, allowing the study of human physiology in organ-specific contexts. One day they will abolish the need for animals in drug development and toxin testing.

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The examination report, titled Organ-on-Chip offers an unmistakable comprehension of the subject matter. The report provides a clear understanding of the market dynamics. The report uses the top-down and bottom-up approaches to define, analyze, and describe the market trends for the upcoming years. The report also tracks the emerging applications, innovative technologies, and mergers & acquisitions.

Competition Analysis: Some of key competitors or manufacturers included in the study are Emulate, TissUse, Hesperos, CN Bio Innovations, Tara Biosystems, Draper Laboratory, Mimetas, Nortis, Micronit Microtechnologies B.V., Kirkstall, Cherry Biotech SAS, Else Kooi Laboratory

Global market, By Type

Liver-on-a-chip

Kidney-on-a-chip

Intestine-on-a-chip

Lung-on-a-chip

Heart-on-a-chip

Other Organs

Global market, By Applications

Pharmaceutical & Biotechnology Companies

Academic & Research Institutes

Cosmetics Industry

Other End Users

Key Questions Answered in Report:

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The report is also equipped with a regional outlook of several global regions such as North America, Europe, Asia-Pacific, Latin America. The Organ-on-Chip Market has been gauged owning to production, manufacturing cost and along with the product specifications. The report thus sheds light on the threats and challenges of the business. . The report has been aggregated on the basis of recent scope, challenges in front of the businesses, and global opportunities to enlarge the sector during the forecast period.

Major Points from Table of Content:

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Organ-on-Chip Market professional study and Future Opportunities: Emulate, TissUse, Hesperos, CN Bio Innovations, Tara Biosystems - Market Expert

GammaDelta Therapeutics is a company that focusses on utilizing the unique properties of gamma delta () T cells to develop novel immunotherapies for patients.Through their research, the companys scientists have discovered a number of targets and antibodies that have the potential to modulate the activity of T-cells in situ. Therefore, GammaDelta Therapeutics recently announced the formation of Adaptate Biotherapeutics, a spin-out company that will focus on research in this area.

Technology Networks spoke with Natalie Mount, CEO of Adaptate BioTherapeutics, to learn more about the company's aims and the challenges faced when developing immunotherapies and advancing them into clinical studies.

Molly Campbell (MC) Please can you tell us more about T-cell based cell therapy products and their potential applications?Natalie Mount (NM): T cells play an increasingly appreciated critical role in immune surveillance, being able to recognize malignant/transformed cells through a pattern of stress markers. The recognition mechanism is not major histocompatibility complex (MHC) restricted and not dependent on a single antigen.

T cells therefore have potential in a range of disease indications, including both hematological and solid malignancies and a positive correlation between T cell infiltration and prognosis/survival in patients has been determined in a range of oncology indications in studies published in the literature by other groups. Additionally, as a cell therapy, T cells can be used in an allogeneic setting (ie, T cells can be used for unrelated recipients without a requirement for matching).

Both Adaptate Biotherapeutics and GammaDelta Therapeutics are focussed on harnessing the potential of T cells, in particular the V1 subtype which is the predominant T cell type in tissue.This is based on data originating from the labs of Professor Adrian Hayday of Kings College London and the Crick Institute, supported by Cancer Research Technology and also from Professor Bruno Silva Santos of Institute for Molecular Medicine at the University of Lisbon, Portugal.

Previous clinical trials conducted by other groups/companies targeting or using T cells in cancer have focussed on the V2 subtype which is predominant in the blood. These trials have demonstrated safety, but efficacy has been limited.Compared to V2 cells, V1 cells, which are the focus of work at Adaptate Biotherapeutics and GammaDelta Therapeutics, are less susceptible to exhaustion and activation induced cell death. Expansion of donor derived V1 has been shown to be a positive prognostic indicator for acute myeloid leukemia patients following hematopoietic stem cell transplant.

MC: Why are current immunotherapy treatment approaches limited?NM: Immunotherapy approaches have had very significant success and impact in Oncology recently, however, challenges and unmet needs remain.One challenge is effective treatment of solid tumors. The hypoxic, low nutrient tumor environment provides a challenge for successful infiltration and activation of T cells. However, V1 T cells have real potential as they are naturally tissue resident and hence primed for this environment. In addition, their ability to recognize malignant cells by a pattern of markers expressed by dysregulated, transformed cells rather than one specific antigen presented by the MHC provides an additional advantage for both specificity of response and maintenance of efficacy.

T cells act as orchestrators of an immune response and, following recognition of a cell as malignant, they induce maturation of monocytes and signal to alpha beta T cells, hence increasing immunogenicity of the tumor and providing a sustained response, with potential even in tumors with low mutational load which have proven challenging with other immunotherapies.

MC: The new spin-out company, Adaptate Biotherapeutics, will build on GammaDelta's knowledge to modulate T-cell activity using therapeutic antibodies. Why have you decided to create a spin-out focusing on this area of research?NM: GammaDelta Therapeutics was formed in 2016 to harness the unique properties of T cells, and since then has gained extensive knowledge of T-cell biology. In addition to gaining insight into cell growth and isolation, the companys scientists have also discovered a number of targets and antibodies that have potential to modulate the activity of T-cells in situ.

GammaDelta Therapeutics now has a pipeline of cell therapy products progressing into clinical development under the guidance of CEO, Dr Paolo Paoletti.

Adaptate Biotherapeutics will be developing antibodies which will be administered to cancer patients to modulate activity of the patient's gamma delta T cells in situ.

Delivery of cell therapy and antibody therapeutics each needs focus and specific skillsets and formation of two independent entities will facilitate this. The two companies share a common goal to harness the potential of T cells to bring effective therapies to patients. Both benefit from support of the scientific founding team and have common investors, Abingworth and Takeda Pharmaceuticals.MC; Your goal is to develop targets and antibodies that can modulate the activity of T-cells and advance them into clinical studies. What challenges exist here, and how do you hope to overcome them?

Our assets at Adaptate Biotherapeutics are currently at the pre-clinical stage and therefore face the non-clinical development risks for a novel therapy. However, these risks are mitigated by biology understanding from our scientific founders and the work at GammaDelta Therapeutics to date.

One of our challenges is in selecting the most suitable patient population for initial trials. There is potential for opportunity for our therapeutics in multiple indications but the utility of animal models in modelling the human immune compartment and human tumor setting is limited. Therefore in vitro and ex vivo models are important, in addition to the learnings from other clinical studies.

MC: GammaDelta Therapeutics formed in 2016 to gain extensive knowledge of T-cell biology and to developing a portfolio of investigational cell therapies. Some of these cell therapies are poised to enter clinical development. Can you tell us any further information about these therapies?NM: GammaDelta was set up to develop cell-based therapy utilizing ex-vivo expanded tissue resident gd T cells. Subsequent acquisition of Lymphact SAS allowed GammaDelta to augment its capabilities with a platform for ex-vivo expansion of blood derived V1 cells. GammaDelta is focussed on progressing ex-vivo expanded skin and blood derived V1 cells to the clinic both in unengineered and engineered formats. Clinical trials are currently on track to commence in the next 12-18 months.

MC: Your press release states: "The two companies will continue sharing their insights into T-cell biology as they work towards developing different therapeutic modalities". How will you continue to share insights here?NM: Antibodies and cells represent complementary approaches to realizing the potential of T cell activity for patients with solid and haematological malignancies.

The two companies will work together in areas of common interest in the biology of these fascinating cells, such as understanding the phenotype and behavior of T cells in tumors and mechanisms of cell regulation as well as the effects of antibody on the T cells.

We have deliberately established a contractual framework that allows efficient collaboration between scientists of both the companies via formal and informal meetings.

MC: What are your hopes for the future of Adaptate Biotherapeutics?NM: This is a remarkable time in the development of new immune therapies, and the role of "non-conventional" cell types of the immune system is coming to the fore as we recognize the successes achieved to date and the needs of patients and related scientific challenges that remain.

Both GammaDelta Therapeutics and Adaptate Biotherapeutics are at the lead of translating our increasing understanding of T cell biology and its potential into therapies to address these unmet needs.

Adaptate Biotherapeutics has a fantastic opportunity to build and accelerate a portfolio of antibody-based approaches in this novel area and I look forward to the successful translation of this science into therapies with the support of our investors at Abingworth and Takeda Pharmaceuticals.

Dr Natalie Mount, CEO of Adaptate Biotherapeutics was speaking with Molly Campbell, Science Writer, Technology Networks.

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Harnessing Gamma T Cells To Bring Effective Therapies to Patients - Technology Networks

The buildup of scar tissue makes recovery from torn rotator cuffs, jumpers knee, and other tendon injuries a painful, challenging process, often leading to secondary tendon ruptures. New research led by Carnegies Chen-Ming Fan and published inNature Cell Biologyreveals the existence of tendon stem cells that could potentially be harnessed to improve tendon healing and even to avoid surgery.

Tendons are connective tissue that tether our muscles to our bones, Fan explained. They improve our stability and facilitate the transfer of force that allows us to move. But they are also particularly susceptible to injury and damage.

Unfortunately, once tendons are injured, they rarely fully recover, which can result in limited mobility and require long-term pain management or even surgery. The culprit is fibrous scars, which disrupt the tissue structure of the tendon.

Working with Carnegies Tyler Harvey and Sara Flamenco, Fan revealed all of the cell types present in the Patellar tendon, found below the kneecap, including previously undefined tendon stem cells.

Because tendon injuries rarely heal completely, it was thought that tendon stem cells might not exist, said lead author Harvey. Many searched for them to no avail, but our work defined them for the first time.

Stem cells are blank cells associated with nearly every type of tissue, which have not fully differentiated into a specific functionality. They can also self-renew, creating a pool from which newly differentiated cell types can form to support a specific tissues function. For example, muscle stem cells can differentiate into muscle cells. But until now, stem cells for the tendon were unknown.

Surprisingly, the teams research showed that both fibrous scar tissue cells and tendon stem cells originate in the same spacethe protective cells that surround a tendon. Whats more, these tendon stem cells are part of a competitive system with precursors of fibrous scars, which explains why tendon healing is such a challenge.

The team demonstrated that both tendon stem cells and scar tissue precursor cells are stimulated into action by a protein called platelet-derived growth factor-A. When tendon stem cells are altered so that they dont respond to this growth factor, then only scar tissue and no new tendon cells form after an injury.

Tendon stem cells exist, but they must outcompete the scar tissue precursors in order to prevent the formation of difficult, fibrous scars, Fan explained. Finding a therapeutic way to block the scar-forming cells and enhance the tendon stem cells could be a game-changer when it comes to treating tendon injuries.

Reference: Harvey, Flamenco and Fan. 2019.A Tppp3+Pdgfra+ tendon stem cell population contributes to regeneration and reveals a shared role for PDGF signalling in regeneration and fibrosis. Nature Cell Biology.DOI: https://doi.org/10.1038/s41556-019-0417-z.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Revolutionizing Injury Recovery With Tendon Stem Cells - Technology Networks

Diversity at least among cancer cells is not a good thing. Now, research from the Weizmann Institute of Science in Rehovot shows that in melanoma, tumors with cells that have differentiated into more diverse subtypes are less likely to be affected by the immune system, thus reducing the chance that immunotherapy will be effective.

The findings of this research, published in Cell, may provide better tools for designing personalized protocols for cancer patients, as well as pointing toward new avenues of research into anti-cancer vaccines.

Prof. Yardena Samuels of the Institutes Department of Molecular Cell Biology wanted to know why, despite the fact that cancer deaths from melanoma have dropped in recent years (thanks to new immunotherapy treatments), many patients do not respond to therapy. The reasons have not been clear, though the leading hypothesis, supported by a few studies, has been that tumors with more mutations are more likely to respond to immunotherapy. Some patients even spend large sums to undergo radiation or chemical treatments to increase tumor mutations, but a causal relationship between the two has not yet been proven.

Samuels and her colleagues were intrigued by studies that suggested a different possible correlation one between heterogeneity (that is, the genetic diversity among tumor cells) and the response to therapy. To investigate this theory, however, the team had to develop a new experimental system to check exactly which factors play a role.

We showed the difference between two extremes highly homogeneous and highly heterogeneous but most cancers fall somewhere in between, says Dr. Bartok. To systematically generate tumors with intermediate levels of genetic heterogeneity, we created a phylogenetic tree of the parental heterogeneous line, and mapped out how subtypes appear over time.

Then we created cocktails of homogeneous cell lines based on this tree, with more or less heterogeneous combinations of cells, and injected them into mice.

As predicted, the more homogeneous the cell cocktail, the easier it was for the mices immune systems to eradicate the cancer, whereas the more heterogeneous the tumors were, the more aggressive they became.

Ultimately, we intend to use the experimental system we created to work on developing applicable personalized protocols for cancer patients, Samuels said.

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Weizmann Institute of Science Works on New Cancer Study Detroit Jewish News - The Jewish News

The air, earth and water of our planet are pulsating with living things. Yet, a vast and diverse web of life exists, about which almost nothing is known.

This is the world of flagellates, tiny organisms that persist in staggering numbers in many diverse ecosystems around the world.

According to Jeremy Wideman, a researcher at the Biodesign Center for Mechanisms in Evolution at Arizona State University, we have a great deal to learn from these delicate and wildly varied creatures. Among other surprises, flagellates could provide valuable clues about a shadowy event that may have occurred 1.5-2 billion years ago, (no one is really sure of the timing), with the arrival of a new type of cell.

Known as LECA, it was a sort of primal egg out of which the astonishing profusion of complex lifefrom flagellate organisms, fungi and plants, to insects, zebra, and humans, exploded and spread over the earth.

In new research appearing today in the journal Nature Microbiology, Wideman and his colleagues, including Prof. Thomas Richards at the University of Exeter describe a new method for investigating the genomes of eukaryotic flagellate organisms, which have been notoriously tricky to pinpoint and sequence.

Specifically, they explored samples of mitochondrial DNA, sequencing around 100 such genomes for previously undocumented flagellates. The new technique could help scientists like Wideman begin to fill in the largely blank region of the eukaryotic puzzle, where flagellate life flourishes.

Cellular worlds

Wideman, originally a traditional cell biologist, became frustrated with the many unaddressed questions in the field, recently joining the emerging discipline of evolutionary cell biology. This rapidly advancing research area uses cells as fundamental units for the study of evolutionary processes and imports concepts from evolutionary biology to better understand how cells work. Im literally a cell biologist that wants to know more about things we know nothing about, he says.

Evolutionary cell biology is a profoundly transdisciplinary endeavor, fusing evolutionary theory, genomics and cell biology with quantitative branches of biochemistry, biophysics, and population genetics.

Flagellates include many parasites implicated in human disease, from the intestinal bug Giardia to more damaging trypanosomes, and leishmania. Flagellates also perform more benevolent tasks. As the major consumers of bacteria and other protists in aquatic ecosystems, they help ensure the recycling of limiting nutrients.

Single-celled eukaryotic organisms, which include flagellates, constitute the overwhelming majority of eukaryotic diversity, vastly outpacing the more familiar multicellular plants, animals, and fungi. Despite their importance and ubiquity across the globe, flagellates are, as Wideman stresses, an almost entirely unknown inhabitant of the living world and one of the most enigmatic. When viewed under a microscope, their often science fiction-like appearance is markedly distinct from the kinds of eukaryotic cells commonly described in biology textbooks. Their emergence from comparatively rudimentary prokaryotes marks the most momentous transition in the history of life on earth.

Novel lineages of heterotrophic flagellates are being discovered at an alarming, rate, Wideman says. In the last two years 2 kingdom level lineages have been discovered (see here and here), meaning lineages that have been evolving independently of animals and fungi for over a billion years. Nevertheless, researchers have barely scratched the surface of this astonishing diversity and new methods must be brought to bear to speed up the quest. (Heterotrophs are organisms that cannot synthesize their own food, relying instead on other organisms for nutrition.)

Microbial safari

Any drop of pond, lake or ocean water is likely to contain many flagellates, but separating them from a multitude of non-flagellates and accurately reading their genomes by conventional means has been slow and painstaking work. Only a minute fraction of extant flagellates have known genomic sequences and its even possible that the overwhelming majority have never actually been seen. According to Wideman, flagellate life forms represent the dark matter of the eukaryotic universe.

Heterotrophic flagellates are the target, Wideman says. Theyre not a lineage. Theyre many, many lineages that are from all over the tree of life. LECA, the Last Eukaryotic Common Ancestor, was a heterotrophic flagellate, which means, that every major lineage (of eukaryotes) evolved from some sort of heterotrophic flagellate.

To access the elusive flagellate mitochondrial DNA, the researchers exploited a feature common to all flagellates and from which they take their namethe existence of flagella, which, unlike in animal sperm are on the front of cells and are often used to pull them forward like a microscopic breast stroke but are also involved in sensation, feeding, and perhaps other, as-yet unknown functions.

Flagella are rich in a particular protein known as tubulin. The new method for identifying flagellates and distinguishing them from their aquatic neighborsprimarily algae and bacteriacapitalizes on this fact by applying a selective stain to flagella-bearing organisms, activated by their high tubulin content. (Algal cells are naturally marked by their chloroplasts, which the flagellates of interest in the new study lack.)

Samples of sea water collected in 2014 off the coast of California provided a test case. Using the technique, the researchers gathered a windfall of mitochondrial sequence data, significantly expanding the catalog of flagellates identified by molecular means. Indeed, they doubled the existing mitochondrial DNA library for flagellate organisms. We got many, many different kinds of organisms. So it was a very rich sample and very few were identical, Wideman says.

In search of LECA

Apart from the mystery of lifes origin, the puzzle of where eukaryotes came from and how the LECA event transpired is the most important and vexing unanswered question in all of biology. (It has been dubbed the black hole at the heart of the living world.)

Correctly establishing the sequence of events underlying the crucial innovations within eukaryotes, from whence all complex life sprang, will take much more research in unexplored regions of the existing eukaryotic domain, particularly, the flagellates. Wideman believes the rapid advance of techniques for identifying and sequencing these organisms, such as the one outlined in the new study, offer hope such questions may one day find answers.

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Aquatic microorganisms offer important window on the history of life - HeritageDaily