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STEVENAGE, U.K.—Globally, more than 10 million units of platelets are transfused every year. Unfortunately, platelets from human donors can transmit infections, and repeated transfusions can result in immune reactions that render the therapy useless, which is known as alloimmune refractoriness.
In an effort to address this issue, Plasticell has developed methods of generating functional platelets from human induced pluripotent stem cells (iPSCs) and scaled them up to intermediate bioreactor level, which enables the manufacture of these products for use in preclinical studies. Plasticell has teamed up with Kings College London in a new partnership focused on preclinical animal trials of the artificial blood platelet product, work which will be supported by a MedCity research grant. Kings College will apply its expertise and in-vivo models to evaluate the dynamics, lifespan, safety and efficacy of the transfused platelets.
“In addition to providing a more stable and safe supply of ‘universal’ platelets, the use of iPS cells would allow us to create immunologically compatible ‘matched’ platelets for patients suffering from alloimmune refractoriness,” commented Dr. Marina Tarunina, principal scientist leading the project at Plasticell.
Plasticell, the company notes, “has used its innovative high-throughput bead-based screening technology CombiCult to discover efficient new methods for the generation of mature megakaryocytes (MKs) and platelets from iPSCs. The production of MK from iPSCs using Combicult technology offers an ability to standardize MK and platelet production procedures and modulate platelet characteristics/phenotype for optimal transfusions.”
“The techniques that we're using are based on the company’s platform technology, which allows it to test very, very large numbers of variables in many combinations to determine optimal conditions to manufacture cellular therapies,” says Dr. Yen Choo, Executive Chairman of Plasticell. “After applying this technology, we're able to derive very robust protocols, where the yield is typically higher than usual, where the cost of goods is lower and where we're able to eliminate costly variables—typically growth factors—from the media that we use. Everything that we do is serum-free, so that takes out further variability.”
“The technology is also able to reduce the time that is typically taken to differentiate pluripotent cells into given cell types, and that reduction in time is obviously good for reducing risk and cost of failure,” he continues. “It's also good for reducing the cost of the therapy, and at the end of the day, in particular with cell products that have competition from donated blood products, such as this, it's very important if you want to reach the market that you have very low cost of the product.”
This work is part of the company’s hematopoietic cell therapy portfolio, which also includes the manufacture of different blood cell types and the expansion of umbilical cord- and bone-derived hematopoietic stem cells. The company notes that success for these preclinical studies would, among other results, consist of the manufactured platelets surviving in the bloodstream without any thromboembolitic events, “while their circulation and tissue distribution profiles should be similar to the ones of the donor platelets.” In addition, “In- vitro results should complement in-vivo observations by demonstrating correct behavior of iPSC-derived platelets at distinct steps of activation response such as adhesion, spreading, aggregation and release reaction to ensure they undergo correct physiological and biochemical changes during hemostatic process.”
In related efforts, Plasticell announced mid-April that it had receive Biomedical Catalyst funding of more than £920,000 from Innovate UK to collaborate with researchers at the University of Edinburgh on developing a red blood cell substitute.
“The attractive thing about red blood cells and platelets is that they're anuclear, so from a pluripotent stem cell perspective, these products are probably going to be the safest products that can be derived from iPS cells,” says Choo.
Plasticell has been chosen by Innovate UK to deliver stem cell R&D projects worth roughly £10 million over the past 10 years.
Choo tells DDNews that, “The total amount of funding in the UK, in Europe, is less than it is in the U.S. But the government here has identified regenerative medicine as one of the technology priorities of the country, and therefore there is a decent amount of money, I'd say, becoming available for this, and we've been very successful in tapping this over a 10-year period.”