Types of Adult Stem Cells – Stem Cell Institute

Stem cells reside in adult bone marrow and fat, as well as other tissues and organs of the body including the umbilical cord. These cells have a natural ability to repair damaged tissue, however in people with degenerative diseases they are not released quickly enough to fully repair damaged tissue. In the case of fat stem cells they may not be released at all. The process of actively extracting, concentrating and administering these stem cells has been shown in clinical trials to have beneficial effects in degenerative conditions. Few patients have access to clinical trials. We offer patients and their doctors access to these therapies now. Stem cell treatments are not covered by insurance.

Adult stem cells can be extracted from most tissues in the body, including the bone marrow, fat, and peripheral blood. They can also be isolated from human umbilical cords and placental tissue. Once the cells have been harvested, they are sent to the lab where they are purified and assessed for quality before being reintroduced back in the patient. Common types of adult stem cells are mesenchymal and hematopoietic stem cells.

Umbilical cord mesenchymal stem cells reside in the *umbilical cords of newborn babies. HUCT-MSC stem cells, like all post-natal cells, are adult stem cells.

The Stem Cell Institute utilizes cord-derived mesenchymal stem cells that are separated from the umbilical cord tissue. For certain indications, these cells are expanded into greater numbers at Medistem laboratory in Panama under very strict, internationally recognized guidelines.

Among many other things, mesenchymal stem cells from the umbilical cord tissue are known to help reduce inflammation, modulate the immune system and secrete factors that may help various tissues throughout the body to regenerate.

The bodys immune system is unable to recognize HUCT mesenchymal stem cells as foreign and therefore they are not rejected. Weve treated hundreds of patients with umbilical cord stem cells and there has never been a single instance rejection (graft vs. host disease). HUCT MSCs also proliferate/differentiate more efficiently than older cells, such as those found in the bone marrow and therefore, they are considered to be more potent.

Through retrospective analysis of our cases, weve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them golden cells.

We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration.

Human umbilical cord tissue-derived mesenchymal stem cells (MSCs) that were isolated and grown in our laboratory in Panama to create master cell banks are currently being used in the United States.

These cells serve as the starting material for cellular products used in MSC clinical trials for two Duchennes muscular dystrophy patients under US FDAs designation of Investigational New Drug (IND) for single patient compassionate use. (IND 16026 DMD Single Patient)

The bone marrow stem cell is the most studied of the stem cells, since it was first discovered to in the 1960s. Originally used in bone marrow transplant for leukemias and hematopoietic diseases, numerous studies have now expanded experimental use of these cells for conditions such as peripheral vascular disease, diabetes, heart failure, and other degenerative disorders.

At Stem Cell Institute, we use purified autologous (patients own) mesenchymal stem cells from bone marrow in our spinal cord injury protocol along with umbilical cord tissue mesenchymal stem cells.

Fat stem cells are essentially sequestered and are not available to the rest of the body for repair or immune modulation. Fat derived stem cells have been used for successful treatment of companion animals and horses with bone and joint injuries for the last 10 years with positive results.

Experimental studies suggest fat derived stem cells not only can develop into new tissues but also suppress pathological immune responses as seen in autoimmune diseases. In addition to orthopedic conditions, Stem Cell Institute pioneered treating patients with osteoarthritis, rheumatoid arthritis, multiple sclerosis, and other autoimmune diseases using fat derived stem cells. However, we no longer use a patients own stem cells from fat because weve found that mesenchymal stem cells from umbilical cord tissue are superior.

Dr. Riordan published the first scientific article on treating humans (3 multiple sclerosis patients) with adipose-derived stem cells. We have treated many patients with adipose-derived mesenchymal stem cells in Panama but we no longer do so because we have found that umbilical cord-derived MSCs modulate the immune system and control inflammation better. HUCT MSCs also proliferate much more efficiently.

Articles Authored by our Doctors and Scientists about Fat Derived Stem Cells:

*All donated cords are the by-products of normal, healthy births. Each cord is carefully screened for sterility and infectious diseases under International Blood Bank standards.

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Types of Adult Stem Cells - Stem Cell Institute

Adult Leukemia: What You Need to Know – Dana-Farber Cancer Institute

Medically reviewed by Richard M. Stone, MD

More than 60,000 new cases ofadult leukemiaare diagnosed in the U.S. each year. Although it is one of the more common childhood cancers,leukemia occurs more often in older adults.

Leukemia is a cancer of the bodys blood-forming tissues that results in large numbers of abnormal or immature white blood cells. The main types of leukemia are:

AML causes the bone marrow to produce immature white blood cells (called myeloblasts). As a result, patients may have a very high or lowwhite blood cellcount, and lowred blood cellsandplatelets.

CLL is the second most common type of leukemia in adults. It is a type of cancer in which the bone marrow makes too many maturelymphocytes(a type of white blood cell).

ALL is a type of leukemia in which the bone marrow makes too many immaturelymphocytes. Similar to AML, the white blood cells can be high or low and oftentimes the platelets and red blood cells are low. This form of leukemia is more common in children than adults.

CML is usually a slowly progressing disease in which too many mature white blood cells are made in the bone marrow.

People with leukemia may experience:

Because these symptoms can be caused by a variety of other conditions, its important to check with your doctor if they arise.

While studies have shown men to be more atrisk than women, some other risk factors include:

While test procedures vary based on the type of leukemia, the two most common procedures are thecomplete blood count(CBC) test and the bone marrow aspiration biopsy.

CBC is a procedure used to check the redblood cell and platelet counts as well as the number and type of white bloodcells (the red cells carry oxygen, the white cells fight and prevent infection,and platelets control bleeding). A bone marrow aspiration biopsy involvesremoving a sample of bone marrow, including a small piece of bone by insertinga needle into the hipbone. The sample is then examined for abnormal cells.

Treatment for leukemia varies depending on the type and specific diagnosis.

The treatment for acute leukemias may be lengthy up to two years in ALL and is usually done in phases. The first phase, known as remission induction therapy, involves administering several chemotherapy drugs over a several-week period. The goal is to destroy as many cancer cells as possible to achieve a remission (in which cancer cells are undetectable, but small amounts are still present).

The second phase, known aspost-remission or consolidation therapy, seeks to kill leukemia cells thatremain after remission induction therapy. This phase may involve chemotherapyand/or a stem cell transplant.

Additional treatments may also be necessary. ALL patients, for example, may receive special treatment to prevent the disease from recurring in the spinal cord or brain.

The treatment for CML has been revolutionized by the advent of the oral medication imatinib and the second- and third-generation drugs known as tyrosine kinase inhibitors (TKIs). These are oral medications that work to inhibit the function of theBCR-ABLprotein. Many patients take these medications for the rest of their lives. In rare instances, a patient may require a stem cell transplant.

Some patients with CLL are recommended formonitoring and observation. Others,usually those with symptoms or low red cell or platelet counts, requiretreatment. Such treatment may involve intravenous chemotherapy, but often withoral therapy with pills that inhibit the function of a key protein, Brutonstyrosine kinase.

Treatments for leukemia can include:

Drugs that harness the immune system in fighting leukemia have shown considerable promise. Some monoclonal antibodies synthetic versions of immune system proteins are already in use to treat certain forms of leukemia and others are being studies in clinical trials.

Another form of immunotherapy, immune checkpoint inhibitors, which release a pent-up immune system attack on tumor cells, is being tested in several forms of leukemia. Cancer vaccines, which boost the immune systems ability to fight cancer, are being studied for use in leukemia.

CAR T-cell therapy, which uses modified immune system T cells to better target and kill tumor cells, has achieved impressive results in trials involving children and adults up to age 25 with relapsed ALL.

Research into new treatments for adult leukemia is moving along several tracks in addition to immunotherapy.

By tracking the specific abnormal genes within leukemia cells, physicians are increasingly able to tailor treatment to the unique characteristics of the disease in each patient. Targeted drugs such as imatinib and dasatinib, for example, are now used in treating patients with ALL whose leukemia cells have an abnormality known as the Philadelphia chromosome. Targeted agents including IDH or FLT3 inhibitors, which zero in on proteins made from mutated genes, have been approved to treat some patients with AML, while other such inhibitors are being tested in clinical trials.

New tests make it possible to detect ever smaller amounts of leukemia that remain after treatment. Investigators are exploring how these minute levels may influence a patients prognosis and how they might impact treatment.

Researchers are testing whether treatment periods for certain drugs can be safely reduced in some patients. For instance, studies are under way to determine if drugs such as imatinib, which are currently taken for life, can be safely stopped in some patients with CML. Researchers hope to test whether treating patients with CLL with the drug ibrutinib plus other medicine for a fixed amount of time is safe and effective.

Patients may consider treatment through a clinical trial.Dana-Farber currently has more than 30 clinical trials for adult leukemia. A national list of clinical trials is available atclinicaltrials.gov.

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Adult Leukemia: What You Need to Know - Dana-Farber Cancer Institute

Hatching disease in a dish: The new frontier in drug testing – Maclean’s

Over lunch at the Canadian Centre for Alternatives to Animal Methods (CCAAM), Charu Chandrasekera nonchalantly mentions one of the projects her team is working on. We are just printing some human liver tissue right now, she says.

Chandrasekera launched the CCAAM at the University of Windsor in 2017, with help from the schools vice-president of research and innovation, Michael Siu, and dean of science, Chris Houser. The centre promotes non-animal methods in biomedical research, education, and regulatory (chemical safety) testing. In October 2019, the centre received a million-dollar gift from the Eric S. Margolis Family Foundation, which Chandrasekera says was instrumental in establishing the state-of-the art research laboratory, and in launching a number of important initiatives.

Chandrasekera says the move away from animal testing to human-based research models isnt radical but inevitable. After many years working in biomedical research with mouse models of heart disease and diabetes, It became very obvious that the work I was doing was not translatable [to humans], she says. Nothing was really reproducible; there were so many discrepancies and contradictions, even among the top-notch researchers.

Ninety-five per cent of drugs tested to be safe and effective in animal models fail in human clinical trials, says Chandrasekera. Alzheimers disease99.6 per cent drug failure rate, she says. It has been cured in mice. But we dont even understand the molecular mechanisms of this disease in humans, much less a cure.

RELATED:I am mine: This is what Alzheimers is like at 41

Empirical evidence from across a whole host of biomedical science disciplines shows us that animal models are failing both science and human health, echoes Elisabeth Ormandy, co-founder and executive director of Animals in Science Policy Institute, a registered Canadian charity working to promote better science without animals. Animal models can falsely show that a drug is effective, she says. They can also falsely show no effect, in which case a drug that would have been shown to be effective in humans never gets advanced to human clinical trials.

The result, she says, is billions of public tax dollars being wasted on research using ineffective animal models, and diversion of precious research funding away from other lines of scientific inquiry that might hold greater promise in terms of predicting drug safety, risk, and effectiveness.

Those other promising lines of scientific inquiry, say Ormandy and Chandrasekera, are human biology-based models. We can use human cells and tissues from cadavers, biopsies, and explanted organs [from surgeries], says Chandrasekera. And we can also engineer them. With adult stem cell technology, you can take a small biopsylike two-to-three millimetres from a persons skinto create any cell type in your body, she says. And if that person has a disease, such as Alzheimers, it will still be present in these cells. These cells can then be assembled to form tissue-like structures called organoids, or engineered through 3D-bioprinting to create more complex tissues, all of which can be combined to create what has become known as disease-in-a-dish. At present,Chandrasekera iscreating diabetes-in-a-dish.

Further, those cells and tissues can also be placed onto computer chips the size of thumb drives, where a large number of drugs can be tested to select whats most appropriate for youpersonalized medicine based on your cells, your tissues, your biologynot mouse biology, Chandrasekera explained in her April 2019 TedX Talk. The goal of the scientific community at large is to create a human-on-a-chip to emulate human biology better than animals, she says, which I think will happen over the next decade.

Currently there is no data on the success rates of human biology-based methods, because there are no drugs that have been approved without animal testing, since animal testing was mandated by regulatory guidelines several decades ago, says Chandrasekera.

However, a growing body of scientific data and internationally approved guidelines in chemical safety testing, indicate that alternative methods are equal or superior to animal models in predicting human biology, Chandrasekera says. Even computer simulations are out-predicting animal-derived data.

RELATED:Health care cannot modernize unless health policy changes first

Ifdisease-in-a-dish and toxicity-on-a-chip effortscontinue to advance at a fast pace with a sense of urgencybacked by global scientific, financial, legislative, and ethical mandates, she says, we will come to a point where we can test drugs without relying on animals.

And while Chandrasekera is busy both in the lab and on the global stage promoting her work, she is also focused on enlightening future scientists. Shes working the development of courses and degrees to train the next generation, she says, to think outside the cage.

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Hatching disease in a dish: The new frontier in drug testing - Maclean's

BrainStorm Cell Therapeutics to make scientific presentations at the 30th International Symposium on ALS/MND – GlobeNewswire

NEW YORK, Nov. 26, 2019 (GLOBE NEWSWIRE) -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leader in the development of innovative autologous cellular therapies for highly debilitating neurodegenerative diseases, announced today that the Company is proud to be a gold sponsor of the 30th International Symposium on ALS/MND.

The symposium will take place December 4 6, 2019, at the Perth Convention and Exhibition Centre in Perth, Australia. The International Symposium on ALS/MND is a unique annual event that brings together leading international researchers and health and social care professionals to present and debate key innovations in their respective fields.

Ralph Kern MD MHSc, BrainStorms Chief Operating and Chief Medical Officer, will deliver a podium presentation: Modulation of innate immunity by MSC-NTF (NurOwn) cells correlates with ALS clinical outcomes, on December 4, from 11:50 12:10 pm AWST during the opening day Clinical Trials Session. In addition to the podium presentation, the Company will also present Poster 153: MSC-NTF Differentiation Increases the Neurotrophic Effects of MSC Cells: Live Imaging Analysis, that directly demonstrates the neuroprotective effects of NurOwn in a neuronal cell culture model.

Our fully-enrolled phase 3 clinical trial is one of the most advanced clinical programs in ALS, stated Chaim Lebovits, President and CEO of BrainStorm. He added, The International Symposium on ALS/MND is an important venue to update the community on our clinical and scientific efforts towards the advancement of therapies that may address the unmet needs of those living with ALS. BrainStorm Cell Therapeutics is proud to serve as a sponsor of this important annual symposium which underscores our commitment to the international community of ALS and MND patients, their families and their caregivers.

Ralph Kern, MD, stated, It is a privilege to present our innovative biomarker and preclinical research at the International Symposium on ALS/MND. He added, Every year, symposium participants gather together and discuss the opportunities and the challenges that we will face during the upcoming year. Research and medical breakthroughs for the ALS and MND community continue to make significant progress and we look forward to sharing our insights and engaging with colleagues from around the globe. The International Symposium on ALS/MND reminds us how far we have come in investigational therapies and how much more progress is still needed to bring patients a better and more promising future.

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors. Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also received U.S. FDA acceptance to initiate a Phase 2 open-label multicenter trial in progressive MS and enrollment began in March 2019.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (U.S. FDA) and the European Medicines Agency (EMA) in ALS. BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six sites in the U.S., supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. For more information, visit BrainStorm's website at http://www.brainstorm-cell.com.

The International Symposium on ALS/MND is a unique annual event that brings together leading international researchers and health and social care professionals to present and debate key innovations in their respective fields. The Symposium is planned as two parallel meetings, one on biomedical research and the other on advances in the care and management of people affected by ALS/MND. Joint sessions consider issues of mutual concern, challenging current views and practices.

Safe-Harbor Statements

Statements in this announcement other than historical data and information constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may," "should," "would," "could," "will," "expect," "likely," "believe," "plan," "estimate," "predict," "potential," and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, risks associated with BrainStorm's limited operating history, history of losses; minimal working capital, dependence on its license to Ramot's technology; ability to adequately protect the technology; dependence on key executives and on its scientific consultants; ability to obtain required regulatory approvals; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

BRAINSTORM CONTACTS:Investors:Uri Yablonka, Chief Business OfficerBrainStorm Cell Therapeutics IncPhone: : +1-201-488-0460Email: uri@brainstorm-cell.com

Media:Sean LeousWestwicke/ICR PRPhone: +1.646.677.1839Email:sean.leous@icrinc.com

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BrainStorm Cell Therapeutics to make scientific presentations at the 30th International Symposium on ALS/MND - GlobeNewswire

Bedfordshire Police officer reunited with woman whose life he saved through stem cell donation – Bedford Today

PC Andrew Harris, who is based at the Police Headquarters in Kempston, signed up to the Anthony Nolan stem cell donor register in 2008 when he joined the Metropolitan Police, he has since transferred to Bedfordshire Police.

Beatrice, a mother of two, from Palm Springs, California, was diagnosed with Myelofibrosis at the age of 23. The condition is a rare type of blood cancer which leads to leukaemia.

She has been living with the condition for the majority of her adult life, managing the symptoms with medication and waiting for a donor match, as this is the only known treatment for this condition.

Her ethnic background Beatrice is half European and half Vietnamese - meant that the chance of finding a match was extremely unlikely, and after years of searching in 2008 she gave up on ever finding a donor to focus her time on taking care of her young children.

Over time her health began to deteriorate and she was in desperate need of a stem cell donation to save her life. So in 2015, when she was about to enter into palliative care, her health care provider ran one last check on the donor register and she received the news that there was a perfect genetic match on a donor list a police officer from the United Kingdom.

At the same time the news came through, Beatrices condition had deteriorated and she was very poorly, thankfully, her health improved enough to get through the transplant procedure.

The transplant was successful and after the two year waiting period, Beatrice and Andrew got in touch through Skype. They have stayed in touch over time and met in person in London a month ago.

PC Harris said: When I was contacted and informed about this match I didnt hesitate for a second. I joined the police because I always wanted to help people and this wasnt any different.

The preparation for the procedure was painless and was done by my doctor and a local nurse. I was given injections for a period of five days to release stem cells into my bloodstream.

After that my stem cells were collected through a special machine similar to a dialysis machine, which was filtering them out of my bloodstream. This was done under local anaesthesia and was completely painless.

If felt unreal when I finally got to meet Beatrice over Skype after the two year waiting period. There was a sense of pride from my side and it was an extremely emotional moment for both of us. Since then we have stayed in touch but we only got to meet in person last month.

It was amazing to meet her and her family. Beatrice is such a strong character and to think that only couple of years ago she and her children were preparing to enter palliative care.

"She is now committed to spreading awareness of how important it is to register as a donor. It is not only one life thats been saved; it is also her family and loved ones who get to keep their daughter, mum and friend.

Our force is working with the local charity and we invite them regularly to events, during which you can join the stem cell register. I would like to encourage everyone who is eligible to sign up; you can be someones last hope and save their life.

People aged between 16 and 30 who are in good general health can sign up to the Anthony Nolan register at http://www.anthonynolan.org.

The charity will send you a swab pack in the post, which you should return to the charity. Whenever a patient with blood cancer or a blood disorder needs a lifesaving stem cell transplant, Anthony Nolan searches the register, looking for someone who is a genetic match for that patient.

If you are found to be a match the charity will be in touch, and will ask you to donate if youre still healthy and happy to do so.

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Bedfordshire Police officer reunited with woman whose life he saved through stem cell donation - Bedford Today

Bedfordshire Police officer reunited with stem cell recipient – Cranfield and Marston Vale Chronicle

A Bedfordshire Police officer has been reunited with a woman whose life he saved after donating stem cells four years ago. Beatrice, a mother of two, from Palm Springs, California, was diagnosed with Myelofibrosis at the age of 23.

The condition is a rare type of blood cancer which leads to leukaemia.

She has been living with the condition for the majority of her adult life, managing the symptoms with medication and waiting for a donor match, as this is the only known treatment for this condition.

Her ethnic background Beatrice is half European and half Vietnamese meant that the chance of finding a match was extremely unlikely. In 2008, after years of searching, she gave up on ever finding a donor to focus her time on taking care of her young children. This was two months before PC Andrew Harris joined the register.

Over time her health began to deteriorate and she was in desperate need of a stem cell donation to save her life.

So in 2015, when she was about to enter into palliative care, her health care provider ran one last check on the donor register and she received the most welcome news. There was a perfect genetic match on a donor list a police officer, PC Harris, from the United Kingdom.

At the same time the news came through, Beatrices condition had deteriorated and she was very poorly. Thankfully, her health improved enough to get through the transplant procedure. The transplant was successful and after the two year waiting period, Beatrice and Andrew got in touch through Skype.

They have stayed in touch over time and met in person in London a month ago.

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Bedfordshire Police officer reunited with stem cell recipient - Cranfield and Marston Vale Chronicle

Keeping cells alive | Interviews – The Naked Scientists

One of the big challenges with making and sustaining organs in the lab is plumbing- getting nutrients in, and waste out. This is the job of the vascular system, that carries blood around the body and is vital to keeping tissues alive.Mark Skylarr-Scott and his colleagues at the Wyss Institute for Biologically Inspired Engineering at Harvard University have recently come up with a new technique for 3D printing large, vascularized human organ building blocks. The technique lays down tracks for blood vessels between clumps of cells to help keep tissues nourished. Using this method, theyve managed to keep clumps of heart cells alive for weeks, which would previously have been almost impossible. Mark took Katie Haylor through the process...

Mark- Step one would be prepare approximately one cup of stem cells. In a lab that involves using something called a bio-reactor to generate vast numbers of stem cells in three dimensions. We then need to instruct those cells to become heart cells. So we put the correct ingredients into this bio-reactor so that they are able to develop into a heart cell.

Mark- So stem cells, and then we provide chemicals that make the stem cells think that they're supposed to develop into beating heart cells. You know, this is a fairly standard process up to this point. And now if we have hundreds of millions of heart cells, a heart isn't a hundred million cells floating around in a bio-reactor. It's actually a solid organ that beats and you know, pumps out blood. We now need to think of a way to compile these together into a tissue.

Mark- So then step two, so we now have hundreds of millions of cells. At the moment, little pieces of tissue. So we actually, they're not single cells, they are in little clumps, about half a millimeter across. If we now take these little clumps and we put them in a centrifuge, we are able to sort of push them all together. We spin them down, they form, a little pellet of cells. Cool it on ice, so it's now at zero degrees.

Mark- We then come with a three D printer and inject gelatin - solid at room temperature and liquid when it's 37 degrees - in three dimensions into this group of cellular aggregates. Now, if this material were liquid, the gelatin would just sink and I wouldn't be able to create a 3D structure. If the material, if my cells were too solid, I would essentially be carving it like a turkey as I come in with a nozzle and 3D printer and inject gelatin in 3D. And this would also break the tissue. But because these cells are halfway between a liquid and a solid, I'm actually able to come in and lay material, this gelatin material in three dimensions and it will hold in place so that when I now raise the temperature, my cells all stick together. So now my tissue is become solid-like, and the gelatin that I printed melts and becomes liquid-like. If I now flush that gelatin out, I'm left with space. I'm left with channels that I can now connect a pump to those channels and actually keep the tissue alive, keep it perfused and viable.

Katie- So it's a bit like a Goldilocks porridge situation. And how does this compare to how a full scale heart would be vascularized?

Mark- This is very different in terms of the process of how we develop, but this is obviously because the goal of creating an organ for transplantation, you can't wait, you know, 20 years for an adult heart to develop, we need to be able to manufacture it quickly. So the process is very different.

Mark- In terms of the architecture, we similarly have blood vessels in our body and in our organ that start very large. The aorta comes from the heart and then it splits and it splits and you're down to what's called arterioles, little arteries. And then the arterioles become capillaries. And then the capillaries rejoin to form veins and then larger veins. Um, so this hierarchical arrangement of blood vessels we're able to reproduce, with a 3D printer - not necessarily at the resolution of capillaries, but certainly in terms of having these branched hierarchical networks.

Mark- This is actually important for transplantation. If a surgeon wants to be able to connect tissue to the patient, they don't want to have a hundred different tubes that they need to suture to connect to be able to feed that tissue. They want a single inlet that will then split, you know, and feed the full volume of the tissue and then a single outlet that they can plumb into.

Mark- I'd say the advantage of our method here is these organoids that are being developed, they really leverage biology's natural ability to make complex structures on their own. The instructions for generating the sort of patterns that you see in organs, of course, it's in our DNA. Organoid protocols, they take advantage of that to form these tissues that can exhibit amazingly complicated architectures that self assemble. They develop on their own for free essentially. So because at the smallest scale we have all of these structures already in place in the organoids, if we can now compile hundreds of thousands of these organoids together into a larger tissue that we can keep alive, we hope that through 3D printing, we get the large scale structures and vasculature necessary to keep it alive, but through developmental biology and the fact that the stem cell derived organoids that have all the microstructure already present, that we get the small scale structure in place as well.

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Keeping cells alive | Interviews - The Naked Scientists