Spanish scientists create a 3D bioprinter to print human skin

This research has recently been published in the electronic version of the scientific journal Biofabrication. In this article, the team of researchers has demonstrated, for the first time, that, using the new 3D printing technology, it is possible to produce proper human skin. One of the authors, José Luis Jorcano, professor in UC3M’s department of Bioengineering and Aerospace Engineering and head of the Mixed Unit CIEMAT/UC3M in Biomedical Engineering, points out that this skin “can be transplanted to patients or used in business settings to test chemical products, cosmetics or pharmaceutical products in quantities and with timetables and prices that are compatible with these uses.”

This new human skin is one of the first living human organs created using bioprinting to be introduced to the marketplace. It replicates the natural structure of the skin, with a first external layer, the epidermis with its stratum corneum, which acts as protection against the external environment, together with another thicker, deeper layer, the dermis. This last layer consists of fibroblasts that produce collagen, the protein that gives elasticity and mechanical strength to the skin.

Bioinks are key to 3D bioprinting, according to the experts. When creating skin, instead of cartridges and colored inks, injectors with biological components are used. In the words of Juan Francisco del Cañizo, of the Hospital General Universitario Gregorio Marañón and Universidad Complutense de Madrid researcher. “Knowing how to mix the biological components, in what conditions to work with them so that the cells don’t deteriorate, and how to correctly deposit the product is critical to the system.” The act of depositing these bioinks, which are patented by CIEMAT and licensed by the BioDan Group, is controlled by a computer, which deposits them on a print bed in an orderly manner to then produce the skin.

The process for producing these tissues can be carried out in two ways: to produce allogeneic skin, from a stock of cells, done on a large scale, for industrial processes; and to create autologous skin, which is made case by case from the patient’s own cells, for therapeutic use, such as in the treatment of severe burns. “We use only human cells and components to produce skin that is bioactive and can generate its own human collagen, thereby avoiding the use of the animal collagen that is found in other methods,” they note. And that is not the end of the story, because they are also researching ways to print other human tissues.

There are several advantages to this new technology.
“This method of bioprinting allows skin to be generated in a standardized, automated way, and the process is less expensive than manual production,” points out Alfredo Brisac, CEO of BioDan Group, the Spanish bioengineering firm specializing in regenerative medicine that is collaborating on this research and commercializing this technology.

Currently, this development is in the phase of being approved by different European regulatory agencies to guarantee that the skin that is produced is adequate for use in transplants on burn patients and those with other skin problems. In addition, these tissues can be used to test pharmaceutical products, as well as cosmetics and consumer chemical products where current regulations require testing that does not use animals.

Universidad Carlos III de Madrid

Scientists discover an unexpected influence on dividing stem cells’ fate

When most cells divide, they simply make more of themselves. But stem cells, which are responsible for repairing or making new tissue, have a choice: They can generate more stem cells or differentiate into skin cells, liver cells, or virtually any of the body’s specialized cell types.
As reported February 3 in Science, scientists at The Rockefeller University have discovered that this pivotal decision can hinge on whether or not tiny organ-like structures, organelles, are divvied up properly within the dividing stem cell.
“In order for the body’s tissues to develop properly and maintain themselves, renewal and differentiation must be carefully balanced,” says senior author Elaine Fuchs, the Rebecca C. Lancefield Professor and head of the Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development.
“Our experiments suggest an unexpected role for the positioning and inheritance of cellular organelles, in this case enzyme-filled peroxisomes, in controlling this intricate balance.”

An uneven division
The outer section of the skin, the epidermis, provides a protective barrier for the body, and stem cells reside deep within it. During development, these cells divide so that one renewing stem cell daughter remains inward while the other daughter differentiates and moves outward to become part of the epidermis’ outer layers. First author Amma Asare, a graduate student in the lab, wanted to know how skin cells first emerge and begin this transition.
Looking in developing mouse skin, Asare devised an approach to identify genes that help guide the balance between new cells that either stay stem-like or differentiate. One particular protein, Pex11b, caught her attention. It is associated with the membrane that surrounds the peroxisome, an organelle that helps to free energy from food.
Asare showed that the protein seems to work by making sure the organelles are in the right locations so they can be divided between the daughter cells. In cells that lacked Pex11b, peroxisomes weren’t divvied up evenly—in some
cases, one daughter cell ended up with all of the peroxisomes and the other didn’t get any at all. And for those cells whose peroxisome distribution was disrupted, cell division took longer, and the mitotic spindle, the structure that separates the daughters’ genetic material, didn’t align correctly.
The net result of depleting skin stem cells of Pex11b, Asare found, was that fewer daughter cells were able to differentiate into mature skin cells.

A delay changes fate
The researchers next moved peroxisomes around in the cell using a sophisticated laboratory technique, and the effect was the same. “If the peroxisomes are in the wrong positions during cell division, no matter how they get there, that slows down the process,” Asare says.
The effect for the whole organism was dramatic:
If peroxisome positioning was disrupted in the stem cells, the mice embryos could no longer form normal skin.
“While some evidence already suggested the distribution of organelles, including energy-producing mitochondria, can influence the outcome of cell division, we have shown for the first time that this phenomenon is essential to the proper behavior of stem cells and formation of the tissue,” says Fuchs, who is also a Howard Hughes Medical Institute Investigator.

The Rockefeller University

Cytotoxic immune cell in sick and healthy skin a key to understanding vitiligo

With the aid of thousands of skin biopsies and over a hundred kilograms of skin, researchers at Karolinska Institutet have observed how two subgroups of immune cell behave in healthy skin. This functional dichotomy is preserved in the inflammatory diseases psoriasis and vitiligo. The study, which is published in the journal Immunity, opens the way for more targeted local treatments for patchy inflammatory skin disorders.

Healthy skin is protected against microbial attack by different kinds of immune cell, including T cells. Patchy inflammatory skin diseases throw the skin’s local immune system out of balance. In people with vitiligo, which causes patchy loss of pigmentation, a certain kind of T cell is dominant in the afflicted areas of skin; patients with psoriasis, on the other hand, exhibit an increase in another kind of T cell.

In the present study, two research groups led by Yenan Bryceson and Liv Eidsmo show how these two subgroups of T cell operate to protect healthy skin from external attacks and retain their unique functions in psoriasis and vitiligo. Doctoral student Stanley Cheuk and colleagues used up to 1,500 skin biopsies per experiment and a total of several hundred kilograms of healthy skin for the critical parts of the study.

Inflammation-causing protein
“By combining the genetic analysis of a small population of immune cells from healthy skin with functional experiments we were able to define two subgroups of memory immune cell and in detail decipher/dissect how these cells behave in healthy and inflamed skin,” explains Liv Eidsmo, researcher at Karolinska Institutet’s Department of Medicine, Solna.

Vitiligo is characterised by the accumulation of a subgroup of T cells called CD49a+, which recognise and are ready to kill pigment cells. In psoriasis, another kind of T cell, CD49a- accumulates in the afflicted skin and produces the inflammation-causing protein IL-17. In healthy skin, CD49a+ and CD49a cells are dormant, but quickly respond with inflammatory and cytotoxic effects when stimulated by IL-15, a protein secreted from skin cells as a rapid-response defence against microbial attack.

“If we can decipher the local immunological changes that give rise to the accumulation of one of the subgroups involved in these patchy skin disorders, we’ll be on the way to more targeted treatments,” says Dr Eidsmo.

The study was financed with grants from the Swedish Research Council, the Ragnar Söderberg Foundation, the Wallenberg foundations, the Swedish Dermatology Foundation and the Swedish Psoriasis Association and through the ALF agreement with Stockholm County Council.

Karolinska Institutet

Important safety information on chemicals still missing

Substances of potential concern were targeted by ECHA’s compliance checks in 2016. Most of the evaluated registration dossiers had data gaps and need updating. The annual evaluation report covers evaluation activities and other measures to improve data quality. It also has recommendations for registrants.

Helsinki, 27 February 2017 – In 2016, ECHA focused its dossier evaluation activities on substances with the greatest potential to negatively affect people and the environment: substances produced in high volumes – over 100 tonnes per year – and with a potential concern.

Last year, 184 new compliance checks were concluded, most of them on selected substances of potential concern. In 168 cases, important information was missing. ECHA asked registrants to provide more data on their substances, mostly related to pre-natal developmental toxicity, mutagenicity/genotoxicity, reproduction toxicity and long-term aquatic toxicity.
To encourage registrants to update their dossiers already before compliance checks or risk management actions take place, ECHA sent letters to the registrants of 270 substances of potential concern, highlighting the deficiencies in their dossiers. The Agency also regularly published a list of substances that may be chosen for compliance checks.

The registration process, in particular the completeness check, was revised to improve the availability of high-quality information in the incoming registrations – both on new ones or existing ones. It now includes manual checks for information that cannot be automatically assessed, ensuring that all information intended by REACH has been included in the dossier.  
If the companies do not react by the deadline stipulated by ECHA, their registration will be revoked.
ECHA’s Executive Director Geert Dancet says: “We have taken an integrated strategic approach to target our regulatory activity on substances of potential concern. Our evaluation report shows that crucial data is still missing for most substances subject to compliance check. I encourage companies to take stock of our recommendations and update their dossiers especially when their substance is shortlisted for regulatory action. Authorities need the data to conclude whether further risk management is required on these substances.”

All testing proposals from the 2013 registration deadline were examined by 1 June 2016 as required by law. Altogether in 2016, ECHA examined 164 new testing proposals and sent 133 draft decisions to registrants. To promote alternatives to animal testing, ECHA now requests registrants submitting testing proposals to provide their considerations on alternatives as part of the registration dossier. New supporting materials on alternative methods were also published.

A large majority of registrants update their dossiers in line with ECHA’s decisions on compliance checks or testing proposals, providing the missing information. Only in 33 of 355 examined cases, information was still missing or inadequate and ECHA invited the Member State authorities to consider national enforcement actions on these registrants.

In substance evaluation, ECHA took 26 decisions based on evaluations from previous years. In preparation of further decisions, Member States evaluated 48 substances in 2015-2016 and concluded that 32 required further information from registrants to clarify the suspected concerns. Furthermore, 20 substance evaluation conclusions were published. 11 of them concluded that the risks are sufficiently controlled with existing measures, and 9 concluded that EU-wide risk management measures are necessary.

The report also gives specific recommendations for future and existing registrants.

ECHA

The first Vitafoods Europe took place in 1997 – there were 100 exhibitors, and just over 1000 attendees. At this year’s event (9 - 11 May at Palexpo, Geneva) we’re expecting over 1000 exhibitors and over 18,500 visitors.

The stature of Vitafoods Europe has grown too. It is now firmly established as the place to be for anyone who wants to do business, network, and source new products and ingredients in the global nutraceutical industry.

There are also opportunities to learn. Visitors are able to discover a wealth of topical compelling content, reflecting the diversity, dynamism and commitment to innovation of the global nutraceutical industry.

If you’re among the 69% of our visitors interested in ingredients and raw materials, I’m confident you’ll find what you’re looking for. Ninety new ingredients will be exhibited and demonstrated in the New Ingredients Zone.
A trip to the International Pavilions will allow you to sample the latest new innovations from across the world.
Running alongside the trade show is the Vitafoods Education Programme. Previously known as the Vitafoods Conference, it will deliver high-value content focused on delegates’ individual needs. If you haven’t already booked your place, you’re strongly advised to do so before 17 March so you can secure an early bird rate.

For delegates seeking high-level technical knowledge, the Programme includes seven R&D Forums which will showcase the latest in applied nutrition science. Meanwhile the Business Workshops will present best practice for business growth, market access and streamlined supply chains.

So Vitafoods Europe 2017 will offer a wealth of cutting-edge, high quality content, with something to meet everyone’s business needs. Whatever you’re looking for, I’m confident you’ll find it at Vitafoods Europe.

For more information about visiting and exhibiting at Vitafoods Europe 2017 visit www.vitafoods.eu.com