̽��ֱ�� of Cambridge - Cedric Ghevaert

First ever clinical trial of lab-grown red blood cell transfusion

cjb250 — Mon, 07 Nov 2022 00:05:46 +0000

̽��ֱ��manufactured blood cells were grown from stem cells from donors. ̽��ֱ��red cells were then transfused into volunteers in the RESTORE randomised controlled clinical trial.

This is the first time in the world that red blood cells that have been grown in a laboratory have been given to another person as part of a trial into blood transfusion.

If proved safe and effective, manufactured blood cells could in time revolutionise treatments for people with blood disorders such as sickle cell and rare blood types. It can be difficult to find enough well-matched donated blood for some people with these disorders.

Chief Investigator Professor Cedric Ghevaert, Professor in Transfusion Medicine and Consultant Haematologist at the ̽��ֱ�� of Cambridge and NHS Blood and Transplant, said: “We hope our lab grown red blood cells will last longer than those that come from blood donors. If our trial, the first such in the world, is successful, it will mean that patients who currently require regular long-term blood transfusions will need fewer transfusions in future, helping transform their care.”

̽��ֱ��RESTORE trial is a joint research initiative by NHS Blood and Transplant and the ̽��ֱ�� of Bristol, working with the ̽��ֱ�� of Cambridge, Guy’s and St Thomas’ NHS Foundation Trust, NIHR Cambridge Clinical Research Facility, and Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust. It is part-funded by a National Institute for Health and Care Research (NIHR) grant.

Professor Ashley Toye, Professor of Cell Biology at the ̽��ֱ�� of Bristol and Director of the NIHR Blood and Transplant Unit in red cell products, said: “This challenging and exciting trial is a huge stepping stone for manufacturing blood from stem cells. This is the first-time lab grown blood from an allogeneic donor has been transfused and we are excited to see how well the cells perform at the end of the clinical trial.”

̽��ֱ��trial is studying the lifespan of the lab grown cells compared with infusions of standard red blood cells from the same donor. ̽��ֱ��lab-grown blood cells are all fresh, so the trial team expect them to perform better than a similar transfusion of standard donated red cells, which contains cells of varying ages.

Additionally, if manufactured cells last longer in the body, patients who regularly need blood may not need transfusions as often. That would reduce iron overload from frequent blood transfusions, which can lead to serious complications.

̽��ֱ��trial is the first step towards making lab grown red blood cells available as a future clinical product. For the foreseeable future, manufactured cells could only be used for a very small number of patients with very complex transfusions needs. NHSBT continues to rely on the generosity of donors.

Co-Chief Investigator Dr Rebecca Cardigan, Head of Component Development NHS Blood and Transplant and Affiliated Lecturer at the ̽��ֱ�� of Cambridge, said: “It’s really fantastic that we are now able to grow enough red cells to medical grade to allow this trial to commence. We are really looking forward to seeing the results and whether they perform better than standard red cells.”

Two people have so far been transfused with the lab grown red cells. They were closely monitored and no untoward side effects were reported. They are well and healthy. ̽��ֱ��identities of participants infused so far are not currently being released, to help keep the trial ‘blinded’.

̽��ֱ��amount of lab grown cells being infused varies but is around 5-10mls - about one to two teaspoons.

Donors were recruited from NHSBT’s blood donor base. They donated blood to the trial and stem cells were separated out from their blood. These stem cells were then grown to produce red blood cells in a laboratory at NHS Blood and Transplant’s Advanced Therapies Unit in Bristol. ̽��ֱ��recipients of the blood were recruited from healthy members of the NIHR BioResource.

A minimum of 10 participants will receive two mini transfusions at least four months apart, one of standard donated red cells and one of lab grown red cells, to find out if the young red blood cells made in the laboratory last longer than cells made in the body.

Further trials are needed before clinical use, but this research marks a significant step in using lab grown red blood cells to improve treatment for patients with rare blood types or people with complex transfusion needs.

John James OBE, Chief Executive of the Sickle Cell Society, said: “This research offers real hope for those difficult to transfuse sickle cell patients who have developed antibodies against most donor blood types. However, we should remember that the NHS still needs 250 blood donations every day to treat people with sickle cell and the figure is rising. ̽��ֱ��need for normal blood donations to provide the vast majority of blood transfusions will remain. We strongly encourage people with African and Caribbean heritage to keep registering as blood donors and start giving blood regularly.”

Dr Farrukh Shah, Medical Director of Transfusion for NHS Blood and Transplant, said: “Patients who need regular or intermittent blood transfusions may result develop antibodies against minor blood groups which makes it harder to find donor blood which can be transfused without the risk of a potentially life-threatening reaction. This world leading research lays the groundwork for the manufacture of red blood cells that can safely be used to transfuse people with disorders like sickle cell. ̽��ֱ��need for normal blood donations to provide the vast majority of blood will remain. But the potential for this work to benefit hard to transfuse patients is very significant.”

Adapted from a press release from NHS Blood and Transplant

Cambridge researchers are taking part in the world’s first clinical trial of red blood cells that have been grown in a laboratory for transfusion into another person.

If our trial is successful, it will mean that patients who currently require regular long-term blood transfusions will need fewer transfusions in future, helping transform their care

Cedric Ghevaert

First ever clinical trial of lab-grown red blood cell transfusion

NHS Blood and Transplant

Cell culture flasks in the incubator during manufacture of red blood cells

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Body builders: collagen scaffolds

lw355 — Wed, 04 Jun 2014 09:07:30 +0000

It may not look like much to the naked eye, but collagen is remarkably strong. ̽��ֱ��most abundant protein in the animal kingdom, it gives strength and structure to skin, tendons, ligaments, smooth muscle tissue and many other parts of the body.

Through precise manipulation at a structural level, collagen can also be used as a construction material in the laboratory or clinic to help regenerate new tissue, repair damaged cartilage and bone, or aid in the development of new therapies for cardiac disease, blood disorders and cancer.

To understand these conditions better and develop new treatments, or regenerate new tissue, researchers require models that very closely mimic the complex, three-dimensional environments found in human tissue.

As a natural material, collagen is ideal for these biomimetic applications. By shaping it into porous structures, collagen acts as a ‘scaffold’ on which cells and tissue can grow in three dimensions in predetermined forms, mimicking those found in the body.

̽��ֱ��idea of using collagen as a scaffold is not new, but the very high level of control that Cambridge researchers are able to achieve over its properties has made a huge range of clinical applications possible, including the repair of damaged joints or tissue, or accelerating the development of new therapies for cancer.

“There is an increasing need for improved materials that work with the systems in the body to regenerate healthy tissue, rather than just replacing what’s there with something synthetic,” said Professor Ruth Cameron of the Department of Materials Science and Metallurgy, who, along with Professor Serena Best, is working with researchers from across the ̽��ֱ�� to develop the scaffolds for a range of clinical applications. “You’re trying to help the body to heal itself and produce what it needs in order to do that.”

To build the scaffolds, the researchers begin with a solution of collagen and water and freeze it, creating ice crystals. As the collagen cannot incorporate into ice, it gathers around the edges of the crystals. When the pressure around the ice is dropped to very low levels, it converts directly from a solid to vapour, leaving the collagen structure behind. By precisely controlling how the ice crystals grow as the water freezes, the researchers are able to control the shape and properties of the resulting collagen scaffold.

By adding small groups of amino acids known as peptide sequences to the surface of the scaffold at different points, the way in which the collagen interacts with the growing cells changes, altering the potential uses for the scaffold. ̽��ֱ��peptide sequences signal certain cells to bind to the scaffold or to each other, while signalling other cells to migrate. Collectively, these signals direct the scaffold to form a certain type of tissue or have a certain type of biological response.

“ ̽��ֱ��scaffolds are a three-dimensional blank canvas – they can then be used in any number of different ways,” said Cameron, who is funded by the European Research Council. “They can be used to mimic the way in which natural tissue behaves, or they can be directed to form different sized or sequenced structures.”

̽��ֱ��technology has already gone from the laboratory all the way to patients, first as Chondromimetic, a product for the repair of damaged knee joints and bone defects associated with conditions such as osteoarthritis, trauma or surgery. By adding calcium and phosphate to the scaffold to mimic the structure of bone, it helps regenerate bone and cartilage. Chondromimetic has been through clinical trials and has received its CE mark, enabling its sale in Europe.

In future, the scaffolds could also see use as a treatment for cardiac disease. Working with Professor Richard Farndale from the Department of Biochemistry and Dr Sanjay Sinha from the Department of Medicine, and supported by funding from the British Heart Foundation, Best and Cameron are developing the scaffolds for use as patches to repair the heart after a heart attack.

Heart attacks occur when there is an interruption of blood to the heart, killing heart muscle. ̽��ֱ��remaining heart muscle then has to work harder to pump blood around the body, which can lead to a thickening of the heart wall and potential future heart failure.

By modifying the collagen scaffolds with the addition of peptide sequences, they could be used to grow new heart cells to ‘patch’ over areas of dead muscle, regenerating the heart and helping it function normally. Cells could be taken directly from the patient and reprogrammed to form heart cells through stem cell techniques.

While the work is still in its early stages, the scaffolds could one day be an important tool in treating coronary heart disease, which is the UK’s biggest killer. “These scaffolds give cells a foothold,” said Farndale, who is working with Sinha to characterise the scaffolds so that they encourage heart cells to grow. “Eventually, we hope to be able to use them, along with cells we’ve taken directly from the patient, to enable the heart to heal itself following cardiac failure.”

Another potentially important application for the scaffolds is in breast cancer research. By using them to grow mimics of breast tissue, the scaffolds could help accelerate the development of new therapies. Working with Professor Christine Watson in the Department of Pathology, Best and Cameron are fine-tuning the scaffolds so that they can be used to create three-dimensional models of breast tissue. If successful, this artificial breast tissue could assist with the screening of new drugs for breast cancer, reduce the number of animals used in cancer research and ultimately lead to personalised therapies.

“This is a unique culture system,” said Watson. “We are able to add different types of cells to the scaffold at different times, which no-one else can do. Better models will make our work as cancer researchers much easier, which will ultimately benefit patients.”

Like breast tissue, blood platelets also require a very specific environment to grow. Dr Cedric Ghevaert of the Department of Haematology is working with Best and Cameron to use the scaffold technology to create a bone-like niche to grow bone marrow cells, or megakaryocytes, for the production of blood platelets from adult stem cells. In theory, this could be used to produce platelets as and when they are needed, without having to rely on blood donations.

“ ̽��ֱ��technology for culturing the cells is actually quite generic, so the range of applications it could be used for in future is quite broad,” said Best. “In terms of clinical applications, it could be used in almost any situation where you’re trying to regenerate tissue.”

“In some senses, it can be used for anything,” added Cameron. “As you start to create highly organised structures made up of many different types of cells – such as the liver or pancreas – there is an ever-increasing complexity. But the potential of this technology is huge. It could make a huge difference for researchers and patients alike.”

Miniature scaffolds made from collagen – the ‘glue’ that holds our bodies together – are being used to heal damaged joints, and could be used to develop new cancer therapies or help repair the heart after a heart attack.

We are able to add different types of cells to the scaffold at different times, which no-one else can do

Christine Watson

Jennifer Ashworth

Collagen scaffold imaged using X-ray microtomography to reveal its 3D structure

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