Cells for Cells US patent granted for bioinspired grafts. An accelerator for the transition from medical research to medical practice

Cells for Cells announces that the U.S. Patent and Trademark Office (USPTO) has granted the patent covering the AUTOMATED FABRICATION OF LAYER-BY-LAYER TISSUE ENGINEERED COMPLEX TUBES (US20180304502).

The approval now legally protects this invention which details a new strategy to fabricate advanced tissue engineered conduits for diverse applications intended to treat major medical conditions that affect millions of people worldwide. Moreover, this new intellectual property milestone positions the company at the forefront of developing innovative technology to address the critical need for vascular grafts.

In particular, the novel approach comprises the use of a robot that can achieve precise geometrical, mechanical and biological personalization of tissue-like conduits thanks to the controlled and automated deposition at high resolution of biomaterials, nanofibers and cells in a unique and rapid one-step fabrication procedure. The personalized tubes manufactured through this patented technology possess a multilayer structure that resembles the anatomy of tissue conduits that are replaced in the treatment of a multitude of different pathologies. Examples of applications that can benefit from these novel tissue conduits include arteries and veins, urethra and intestinal tissues.

Typically, the production of Tissue Engineered Products requires multiple steps that go from scaffold fabrication to cell seeding, maturation in bioreactors, and, ultimately, packaging, making the manufacturing of such solutions a long and inefficient process, which is, moreover, expensive and difficult to standardize. These manufacturing issues have been pointed out in the last years as the main drawbacks that are keeping advanced tissue engineered medical solutions commercially unfeasible and away from the clinical reality.

Aware of the aforementioned challenges, Cells for Cells Tissue Engineering and Biomaterials Unit led by Juan Pablo Acevedo, has worked to bring these tubular grafts closer to patients via the newly patented manufacturing approach. This allows for scalable tissue conduits to be ready to implant in less than an hour with guaranteed standardization and quality. The approach, which has been highlighted in prominent peer-reviewed scientific journals (Akentjew et al., Nature Communications, 2019), solved for the first time technical and commercial issues of the field and makes possible the quick manufacturing of very-needed tissue conduits near the point of treatment.

Cells for Cells and Austrianova announce publication on novel method to produce stem cell exosomes

Austrianova and Cells for Cells have just jointly published a ground breaking, peer reviewed, scientific publication on a novel, cost and time-saving method to generate extra-cellular vesicles (EVs) from encapsulated Mesenchymal Stem Cells (MSCs). These EVs are known to mediate many of the therapeutic effects of stem cells. The authors show that Austrianova’s proprietary Cell-in-a-Box encapsulation technology can be used to produce and deliver EVs from encapsulated MSC’s, as demonstrated using Cells for Cells proprietary MSCs.  The publication, which was co-authored with their academic partners, the University of the Andes, Chile and the University of Veterinary Medicine Vienna, Austria appeared in prestigious international journal “Frontiers in Pharmacology” (Front. Pharmacol., 21 May 2020 | https://doi.org/10.3389/fphar.2020.00679   https://www.frontiersin.org/articles/10.3389/fphar.2020.00679/full)

Currently, EVs have to be purified from cell culture conditioned media using tedious, costly and time-consuming protocols that are difficult to perform under Good Manufacturing Practices (GMP) conditions. The Cell-in-a-BoxÒ encapsulation technology allows efficient enrichment of EVs at high concentration since they are released from the encapsulated cells via the semipermeable pores, which selectively enable the release of small particles but not of the MSCs. Moreover, Cell-in-a-BoxÒ provides 3D culture conditions for the MSCs. The technology can be used in cell culture allowing GMP production. Alternatively, the encapsulated cells can be implanted into patients as a retrievable delivery device that shields the cells from clearance, whilst they continuously produce EVs, growth factors, hormones and other small therapeutically relevant molecules. Moreover, the EVs produced after encapsulation can themselves be used as drug-loaded delivery vehicles. This technology will be invaluable for the treatment of regenerative diseases and Inflammatory disease.

Source: EPR BIOTECH NEWS

New automated technology for small diameter vascular grafts fabrication developed by Cells for Cells

  • The study, conducted by the Chilean biotech company Cells for Cells was published in Nature Communications journal.
  • The automated approach allows the assembly of bio-inspired structural configurations enabling the fabrication of small-bore grafts that exhibit mechanical response and compliance of human coronary arteries.

Global deaths attributed to cardiovascular disease are expected to reach 22.2 million in 2020 owing to an increasing aging population. Though standard treatment and best alternative for bypass surgeries are autologous vessels, the harvesting of the patient’s vessels is limited due to length, low quality tissue, and the considerable morbidity associated. On the other hand, synthetic alternatives are strongly limited for small diameter vessels because of thrombosis caused by natural vessel/blood–graft interface contact.

Different approaches have been reported proposing new strategies for the fabrication of vascular grafts using natural, synthetic and hybrid materials, from xenogeneic vessels to bioprinted alternatives. However, few of them exhibit the mechanical response to resemble a native vessel, and/or show a non-homogeneous cell seeding throughout the scaffold.

Researchers from Cells for Cells combined a mimicry of the tri-layered structure of native arteries, including the orientation of fibres in each layer and the distribution of different concentric cells with the aim of recapitulating the mechanical properties in a ready-to-use graft that can be rapidly fabricated in an automated process. The study was recently published in the prestigious journal Nature Communications (https://www.nature.com/articles/s41467-019-11090-3#article-info), demonstrates the fabrication of small diameter vascular grafts using the combination of spinning techniques, which are capable of depositing fibres at defined angles and impart fibre waviness. The mechanical match to native tissue in each layer was achieved by mimicking fibre angles and tuning vessel thickness, enabling close resemblance to the deformation profile and compliance of human coronary arteries. Specific cell types can be encapsulated to impart biological function to the construct, with homogeneous distributions in concentric gelatin-alginate layers. Juan-Pablo Acevedo, the senior author of the project, clarifies that ” the advances we bring to the vascular graft field reside in both its cost-effectiveness and scalability, since the final product is presented as a ready-to-use biohybrid graft. We designed this technology to efficiently address the unmet medical need allowing the accelerated patients’ access to our grafts”.

“We feel very proud of the world-class R&D being developed in Cells for Cells. Currently, we are focusing our efforts on finding adequate solutions targeting diseases for which no treatment is available. While there is still a long translational pathway ahead, this milestone represents an important step towards completing our vision as a leading biotech company with international renown in research, development and commercialization of cutting-edge cell therapy technologies. We believe that they will be accessible to a large part of the population in the coming future”, says Maroun Khoury, CSO of Cells for Cells.

A Chilean cell-based clinical trial in osteoarthritis reveals the superiority of repetitive MSC injections to Hyaluronic Acid treatment

  • The study, made by the Chilean biotech company Cells for Cells and Universidad de los Andes Clinical Center, was published in STEM CELLS Translational Medicine journal.
  • The work shows that patients with knee osteoarthritis treated with the allogeneic umbilical cord MSC-based therapy branded as CELLISTEM® OA, experienced a significant improvement in pain reduction, increased mobility and decreased stiffness.

Santiago, January 2019

Researchers from Cells for Cells and Universidad de los Andes Clinic, developed a therapy for the symptomatic treatment of osteoarthritis, using mesenchymal cells from umbilical cord stroma.
Between 2015 and 2017, Cells for Cells and its government co-financed research consortium Consorcio Regenero conducted a clinical trial entitled: “Allogeneic Mesenchymal Stromal Cell therapy for knee-OA: A phase I/II randomized controlled trial”. The study design compared the efficacy and safety of CELLISTEM® OA versus hyaluronic acid as a treatment for symptomatic knee osteoarthritis in 30 Chilean patients between 40 and 65 years old.

In terms of pain, CELLISTEM® OA was much superior to Hyaluronic Acid at 6 and 12 months of follow-up. Two doses of CELLISTEM® OA with an interval of 6 months between doses, is the treatment that obtained the greatest benefits, with an 85% of pain reduction.

In terms of joint function, CELLISTEM® OA was also significantly superior to Hyaluronic Acid at 6 and 12 months of follow-up. A dose of CELLISTEM® OA repeated at 6 months had better results, with a relative reduction of 90% joint disability.

The percentage of responder patients measured by the OMERACT-OARSI Responder Index Criteria was also significantly higher with CELLISTEM® OA, obtaining a 100% response in patients who received the treatment twice a year.

Francisco Espinoza, medical director of Cells for Cells and rheumatologist at Universidad de los Andes Clinic, said that the work from many years has the explicit support of the specialized scientific community. In addition, indicated that with the team of researchers “we are encouraged by these results, because they could pave the way for a new non-invasive therapy, which improves the quality of life of a group of patients that currently face very limited therapeutic options.”

The scientific journal STEM CELLS Translational Medicine is one of the journals with the greatest impact in cell therapy, which supports the thoroughness of the clinical trial, the only one of its kind worldwide. This is the second clinical study originated in Chile which uses stem cells, after the publication, on September 2017, of the clinical study RIMECARD, also from Cells for Cells, in the scientific journal Circulation Research Journal of the American Heart Association (AHA).

Before to the study in patients, there was an extensive preclinical research work in the laboratory to support the safety and efficacy of this therapy and to unravel its possible action mechanisms.
For Maroun Khoury, scientific director of Cells for Cells, “the symptomatic improvement of osteoarthritis may be associated not only with the high regenerative capacity and differentiation of cells derived from umbilical cord, but also with its immunoregulatory effect or even with new mechanisms of action that we are still elucidating. Through these factors we can select which cells have a better effect in one or another pathology, such as knee osteoarthritis or heart failure”, he says.

Osteoarthritis of the knee is one of the main causes of pain and disability. While conventional treatments show modest benefits, the aim of this study was to evaluate the safety and efficacy of single or repeated intra-articular injection of mesenchymal cells derived from umbilical cord and selected for their regenerative potential, through an allogenic treatment, that is with stem cells from a donor and not from the same patient.

International recognition

The publication of this clinical trial supports the development of innovative cell therapies and the work Cells for Cells is doing in this field. Cells for Cells set to begin a multicenter Phase III clinical trial with neighboring countries during 2019, while preparing the ground for entering in other geographical regions.

“This is the result of a long-standing work of a team of professionals committed to innovation, which includes research and development of an advanced medical therapy that has clinical support and intellectual property protection. We are very happy and satisfied with this milestone, because we are not only making progress in the area of cell therapy, but we are helping to improve the quality of life of many people who without this therapy would not have many treatment options”, says Roberto Bobadilla, CEO of Cells for Cells and Consorcio Regenero.

 

Clinical trial: “Allogeneic Mesenchymal Stromal Cell therapy for knee-OA: A phase I/II randomized controlled trial”

Strong attendance, new regulation and growing regional interest mark the annual meeting of the Brazilian Association for Cell Therapy (ABTCEL)

A total of 277 attendees, a record number of 128 selected abstracts and 56 national and international speakers were the figures bolstering up the growing interest for cell therapy in the SCA region.

ISCT participated in this successful event, in Sao Paulo, through a joint session focusing on clinical applications. The ISCT awards for best presentations included a free registration for the annual meeting of the society in Melbourne for 2019. Maroun Khoury and Patricia Rocco regional VP and VP elect, were the officers representing the ISCT and participated in the scientific committee.

According to Milena Soares, the actual President of ABTCEL “the current and future interaction of ABTCEL with ISCT may contribute to strengthen the cell and gene therapy field in Brazil and promote new interactions with other Latin American countries”. A presentation exposed by the Brazilian regulatory agency (ANVISA) announced the new regulation for advanced therapies. The round table discussion around this topic concluded that this new frame will facilitate the approval of cell based therapies in the country.

Dr. Khoury presented the society’s main pillars of values, commenting that “a special effort was done to obtain reduced membership rates for the region, this opens the possibility for researchers in emerging countries to overcome their financial limitations and join the ISCT effort in driving a strong and regulated cell therapies for the benefit of patients in the region”.

 

Photo: Antonio De Carvalho (VP ABTCEL), Milena Soares (P ABTCEL), Patricia Rocco (Regional VP-elect ISCT) Maroun Khoury (Regional VP -ISCT)

Cardiac risk in Chileans How do we help to face this challenge?

At the end of January, the Ministry of Health announced the second delivery of the results of the National Health Survey (ENS). Among other indicators, it reveals that 25.5 percent of the Chilean population is in the category of high cardiovascular risk. The are many factors and, without a doubt, it is an important challenge that should not only be addressed by the next health authorities, but should be considered in the public policies of the country.

In this scenario, it is necessary to think of innovative treatments that help to alleviate the associated costs, in order to improve their cardiac function and above all, help patients with heart failure to improve their quality of life. With this objective, Chilean researchers from Cells for Cells, a Chilean biotechnology company associated with the Universidad de los Andes, have developed Cellistem®IC, a cell therapy based on mesenchymal cells of the umbilical cord that is administered to the patient intravenously, and ambulatory way. The therapy, whose clinical study was published in the American Heart Association’s Circulation Research Journal, has been administered to patients who showed a significant improvement in their ability to pump blood, and cataloged by specialists as a practical, simple, universal treatment.

In Chile, heart failure affects 16% of the population over 75 years of age, with a mortality that exceeds breast or prostate cancer. Its therapy is limited to pharmacological, surgical and through different devices, such as ventricular resynchronization and the artificial heart, even reaching cardiac transplantation.

Mega showed the history of the Chilean fencer Rubén Silva

Rubén Silva opted by cell therapy. Four years ago, he began to suffer sporadic pains in his wrist that were presented in certain activities that required effort, something unexpected and decisive to practice the sport that he is passionate about and which he is one of the best exponents in Latin America, fencing. When the discomfort began to increase, he was diagnosed and treated with traditional therapies with which he only obtained partial results.

In 2015, during a trip to the United States, the pain prevented him from competing. Finally, at the end of that year he was diagnosed with a radiocarpal osteochondral lesion and osteoarthritis of the ulnar-distal area. Considering that it was an irreversible injury, with discomfort that continued to increase and that he was already 30 years old, Rubén thought about retiring.

Then, he decided to prove cell therapy that had been recommended. As a good doctor, he was informed about evidence level and without hesitation he placed himself in the hands of Dr. Sebastian von Unger, a traumatologist at the Clinic of the University of the Andes. “The discomfort began to decrease, slowly but progressively, which allowed me to train and achieve results that I had not achieved before”, emphasizes Rubén. “Now I am a South American champion and probably, without this treatment, I would have retired without being able to perceive this achievement”.

“Finally the therapy gave the results I expected, gave me a second air, and allowed me to continue enjoying this sport.”

In the press

Mega, highlighted the story of Rubén Silva, who like Rafael Nadal and Cristiano Ronaldo, cell therapy has been effective in recovering injuries.

Nueva Mujer magazine highlighted Miacell therapy

The therapy, developed by Cells for Cells, is highlighted as part of a story informing about new facial rejuvenation treatments with high technology. The story, says that the facial treatments destined to rejuvenate the skin are increasingly advanced and painless. Miacells stands out as a non-invasive procedure, which leaves no visible traces and allows the activities to be resumed on the same day – or maximum the day after – of the intervention.

Check the story here

Cells for Cells’s clinical trial highlighted in El Mercurio

On December 26, the newspaper El Mercurio published a note about Cellistem®IC, our clinical trial of cell therapy with positive results for the treatment of heart failure.

See the story

Primera patente otorgada a C4C: construcción de la protección de nuestra propiedad intelectual

Cumpliendo un primer ciclo que comenzó el año 2013 con las primeras solicitudes internacionales de patentes, el 1° de noviembre de 2017, Cells for Cells recibió la concesión de su primera patente. Otorgada por la European Patent Office, la invención “Menstrual Stem Cells for the efficient support and expansion of CD34 + CD133 + hematopoietic stem cells in vitro”, fue desarrollada por los inventores Maroun Khoury y Francisca Alcayaga.

La patente, que describe el método para cultivar y proliferar células madre hematopoyéticas y menstruales, es un hito en la historia de Cells for Cells, ya que permite la protección intelectual base de lo que se desarrollará hacia adelante. Si bien esta patente no tiene un fin comercial directo, es la base para proteger la propiedad intelectual de nuestra empresa y, desde ahí, fundamentar nuestros desarrollos tecnológicos.

Cabe destacar que, para solicitar una patente, la invención debe contar con tres requisitos: ser novedosa, tener un nivel inventivo y aplicabilidad industrial. Así, el trabajo con células mesenquimales de fluido menstrual ha sido uno de los desarrollos tecnológicos que nos ha diferenciado de otras empresas pertenecientes a la industria.