The blood stem cell research that could change medicine of the future


Making stem cells from a patient’s adult cells – rather than human embryos – is one of the holy grails in modern medicine treatments. New research brings us two steps closer.

Biomedical engineers and medical researchers at UNSW Sydney have independently made discoveries about embryonic blood stem cell creation that could one day eliminate the need for stem cell blood donors.

The achievements are part of a move in regenerative medicine towards the use of ‘induced pluripotent stem cells’ to treat disease, where stem cells are reverse engineered from adult tissue cells rather than using live human or animal embryos.

But while we have known about induced pluripotent stem cells since 2006, scientists still have plenty to learn about how cell differentiation in the human body can be mimicked artificially and safely in the lab for the purposes of delivering targeted medical treatment.

Two studies have emerged from UNSW researchers in this area that shine new light on not only how the precursor blood stem cells occur in animals and humans, but how they may be induced artificially.

In a study published today in Cell Reports, researchers from UNSW School of Biomedical Engineering demonstrated how a simulation of an embryo’s beating heart using a microfluidic device in the lab led to the development of human blood stem cell ‘precursors’, which are stem cells on the verge of becoming blood stem cells.

And in an article published in Nature Cell Biology recently, researchers from UNSW Medicine & Health revealed the identity of cells in mice embryos responsible for blood stem cell creation.

Both studies are significant steps towards an understanding of how, when, where and which cells are involved in the creation of blood stem cells. In the future, this knowledge could be used to help cancer patients, among others, who have undergone high doses of radio- and chemotherapy, to replenish their depleted blood stem cells.

Emulating the heart

In the study detailed in Cell Reports, lead author Dr Jingjing Li and fellow researchers described how a 3cm x 3cm microfluidic system pumped blood stem cells produced from an embryonic stem cell line to mimic an embryo’s beating heart and conditions of blood circulation.

She said that in the last few decades, biomedical engineers have been trying to make blood stem cells in laboratory dishes to solve the problem of donor blood stem cell shortages. But no one has yet been able to achieve it.

“Part of the problem is that we still don’t fully understand all the processes going on in the microenvironment during embryonic development that leads to the creation of blood stem cells at about day 32,” Dr Li said.

“So we made a device mimicking the heart beating and the blood circulation and an orbital shaking system which causes shear stress – or friction – of the blood cells as they move through the device or around in a dish.”

These systems promoted the development of precursor blood stem cells which can differentiate into various blood components – white blood cells, red blood cells, platelets and others. They were excited to see this same process – known as haematopoiesis – replicated in the device.

Study co-author Associate Professor Robert Nordon said he was amazed that not only did the device create blood stem cell precursors that went on to produce differentiated blood cells, but it also created the tissue cells of the embryonic heart environment that is crucial to this process.

“The thing that just wows me about this is that blood stem cells, when they form in the embryo, form in the wall of the main vessel called the aorta. And they basically pop out of this aorta and go into the circulation, and then go to the liver and form what’s called definitive haematopoiesis, or definitive blood formation.

“Getting an aorta to form and then the cells actually emerging from that aorta into the circulation, that is the crucial step required for generating these cells.”

“What we’ve shown is that we can generate a cell that can form all the different types of blood cells. We’ve also shown that it is very closely related to the cells lining the aorta – so we know its origin is correct – and that it proliferates,” A/Prof. Nordon said.

The researchers are cautiously optimistic about their achievement in emulating embryonic heart conditions with a mechanical device. They hope it could be a step towards solving challenges limiting regenerative medical treatments today: donor blood stem cell shortages, rejection of donor tissue cells, and the ethical issues surrounding the use of IVF embryos.

“Blood stem cells used in transplantation require donors with the same tissue-type as the patient,” A/Prof. Nordon said.

“Manufacture of blood stem cells from pluripotent stem cell lines would solve this problem without the need for tissue-matched donors providing a plentiful supply to treat blood cancers or genetic disease.”

Dr Li added: “We are working on up-scaling manufacture of these cells using bioreactors.”

Mystery solved

Meanwhile, and working independently of Dr Li and A/Prof. Nordon, UNSW Medicine & Health’s Professor John Pimanda and Dr Vashe Chandrakanthan were doing their own research into how blood stem cells are created in embryos.

In their study of mice, the researchers looked for the mechanism that is used naturally in mammals to make blood stem cells from the cells that line blood vessels, known as endothelial cells.

“It was already known that this process takes place in mammalian embryos where endothelial cells that line the aorta change into blood cells during haematopoiesis,” Prof. Pimanda said.

“But the identity of the cells that regulate this process had up until now been a mystery.”

Read more: Baby mice have a skill that humans want – and this microchip might help us learn it

In their paper, Prof. Pimanda and Dr Chandrakanthan described how they solved this puzzle by identifying  the cells in the embryo that can convert both embryonic and adult endothelial cells into blood cells. The cells – known as ‘Mesp1-derived PDGFRA+ stromal cells’ -– reside underneath the aorta, and only surround the aorta in a very narrow window during embryonic development.

Dr Chandrakanthan said that knowing the identity of these cells provides medical researchers with clues on how mammalian adult endothelial cells could be triggered to create blood stem cells – something they are normally unable to do.

“Our research showed that when endothelial cells from the embryo or the adult are mixed with ‘Mesp1 derived PDGFRA+ stromal cells’ – they start making blood stem cells,” he said.

While more research is needed before this can be translated into clinical practice – including confirming the results in human cells – the discovery could provide a potential new tool to generate engraftable haematopoietic cells.

“Using your own cells to generate blood stem cells could eliminate the need for donor blood transfusions or stem cell transplantation. Unlocking mechanisms used by nature brings us a step closer to achieving this goal,” Prof. Pimanda said.

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What Is the Future of the Stem Cell Market in 2022?


Stem cell therapy continues to rally worldwide recognition as governments fund research and expand access. This once-controversial therapy is fast becoming one of medicine’s most exciting technologies. From FDA-approved therapies to in-house, physician-initiated autologous techniques, stem cell technology continues to evolve. 2022 promises to be an exciting year for the stem cell market.

The Stem Cell Market in 2022 and Beyond

Government and private funding is the main engine behind stem cell therapy’s persistent growth. Robust research has led to advances in all types of regenerative therapies, with stem cell technology at the forefront.

If anybody doubts the future of stem cells, they should look at their soaring market potential. Here are the top nine driving forces behind the stem cell market’s accelerating momentum.

1. Oncology Applications

While treating cancer with stem cells is not new, the field of cancer treatment is where stem cell therapy excels. With an aging population comes a global rise in cancer rates. While stem cell therapy can help treat certain forms of cancer, it has also proved helpful in combating the damaging effects of chemotherapy.

For over 50 years, hematopoietic stem cell transplants (HSCT) derived from bone marrow or cord blood have been used to treat many cancer forms. Hematopoietic stem cells are widely used in cancer treatments. The key to their popularity? Their ability to form a variety of cell types that constitute our blood and immune system.

Bone marrow transplants have been used to treat cancers such as:

  • Multiple myeloma
  • Neuroblastoma
  • Leukemia
  • Lymphoma (certain types)

Also, scientists and clinicians are learning how to better genetically match and administer these cells, as well as care for patients after stem cell transplantation. The result is the prevention of dangerous conditions like graft versus host disease (GvHD).

2. Dermatology

Dermatology is another area that lends itself to stem cell adoption. Autologous epidermal stem cells can treat various types of skin conditions, including severe burns. Renovacare’s Skin Gun™ is an example of a technology that uses the patient’s own skin as a stem cell source. A doctor can take a sample of a patient’s skin and place it in the Skin Gun™. The device “blends” the sample into a solution, which then can be sprayed as a thin mist on the affected area. The result is that the burn area readily accepts the genetically-similar sample and can go about regenerating skin locally.

Other dermatology conditions that can make use of stem cell therapy include wound healing, treatment of severe blistering, and skin manifestations of autoimmune diseases.

3. Regenerative Medicine

Stem cell therapy is, by definition, regenerative. But what about its applications for overall human longevity? If you want to get a glimpse into what the future holds for stem cell therapy, consider that stem cells may hold the key to staving off chronic disease as well as replacing old organs.

The net result? A drastically-slowed rate of aging and an average life expectancy well into one’s 80s (and beyond). It is said that the first human who will live to two hundred has already been born. Stem cell technology will undoubtedly play a large role in the long life of future generations.

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What Is the Future of the Stem Cell Market in 2022?





Cell Therapies Hit Their Stride

It’s been about half a century since the first transplant of bone marrow from a donor to a recipient was completed. Since then, bone marrow transplantation has become an integral part of care for many patients with persistent leukemia, lymphoma, multiple myeloma and other blood cancers, as well as noncancerous blood disorders such as sickle cell disease. Specifically, we are transplanting stem cells — nascent cells with the capacity to mature into functioning blood and immune system cells — from a matched or partially matched donor into the body of a patient whose own blood-forming system has been destroyed with toxic medication to make way for a healthy new system to grow and develop.

In recent years, however, our field has expanded to include other treatments that work in similar ways as bone marrow transplantation. They are collectively known as “cellular therapies” because they do one of three things: provide healthy new cells to replace diseased cells, release an influx of specially modified immune cells to teach the body’s immune cells how to fight disease, or provide cells that connect immune cells with cancer cells they are designed to kill. Study after study has demonstrated how these approaches are extending patients’ lives. This progression of therapies is reflected in bone marrow transplant services around the country, many of which — including our own at Hackensack University Medical Center — now include the words “cellular therapy” in their names.

It is an exciting time for those of us in the stem cell transplantation and cellular therapy field. For years, we have concentrated on improving the outcomes of stem cell transplants. We have significantly improved techniques to reduce the risk of graft-versus-host disease, a potentially serious complication of transplantation that occurs when immune cells from the donor identify the tissues of the recipient as foreign and attack them, causing a host of inflammatory symptoms. We have learned which medications to give to prevent post-transplant infections such as cytomegalovirus, a common virus that can be damaging in people with compromised immune systems. We are using stem cells from umbilical cord blood to perform more transplants in adult patients. And we have matched more patients with donors by learning how to perform “haploidentical” transplants, where the patient receives a transplant from someone who is partially matched immunologically. These advances are making stem cell transplantation a safer and more effective treatment option for more patients who need them.

But where we are really seeing a revolution in care is the field of cellular therapy — particularly CAR T-cell immunotherapy. Cancer cells have found ways to escape being detected and destroyed by immune cells. Immunotherapies work by helping the immune system find and kill cancer cells.

With CAR T-cell therapy, immune cells called T cells are removed from the patient, genetically modified in a lab to recognize and attach to certain targets on cancer cells, grown to larger quantities (hundreds of millions), and returned to the patient. There, the modified T cells can find, bind to and kill cancer cells. The treatment is given intravenously. Long after the patient goes home, however, his or her newly educated immune cells continue to detect and destroy cancer cells, which is why this treatment is often referred to as a “living therapy.”

CAR T-cell therapies are typically administered in bone marrow transplantation units, and for good reason: Patients receive chemotherapy beforehand, which reduces the immune response. The treatment itself can cause immunologic side effects which, albeit temporary, can be severe — including high fever, body aches and chills. The administration of CAR T-cell therapies requires round-the-clock care from a specially trained and credentialed team. As bone marrow transplant specialists, our experience and knowledge of immunology enable us to recognize and manage the inflammatory complications that may result.

Current CAR T-cell therapies are FDA-approved for the treatment of recurrent or persistent diffuse B-cell lymphoma, follicular lymphoma, multiple myeloma and mantle cell lymphoma (which is a very aggressive and challenging cancer) in adults, as well as acute lymphoblastic leukemia in children and young adults up to age 25. We are intrigued by other innovative cellular therapies under study in clinical trials, such as natural killer (NK) cells and tumor-infiltrating lymphocytes (TILs). These treatments are made from a patient’s own tumor tissue, so it has already been exposed to the patient’s own immune system. Immune cells within a tumor, which on their own were unable to kill the cancer, are isolated from tumor tissue removed during surgery, modified and multiplied in a lab, and returned to the patient with other medications to boost the immune response against cancer.

Not only is the technology getting better, but the types of tumors we are treating is broadening. New CAR T-cell therapies, NK and TIL treatments, and another approach that combines CAR T-cell and NK therapies may broaden the application of these “living therapies” to patients with solid tumors, including melanoma, breast cancer and pancreatic cancer. We’re also looking at combining cellular immunotherapies with stem cell transplantation to augment the anticancer immune response even further.

Cellular therapies are truly game-changers in cancer care. It has been inspirational for us as bone marrow transplant professionals to be part of their development. What we’re witnessing now is just the tip of the iceberg. We’re only getting better at identifying the best immune cells and engineering them in the best fashion to harness the immune system in the most effective way. Discovery is exponential and the field of immunotherapy is growing at warp speed. It’s not impossible to think that we’re going to be curing cancer.

Michele Donato, MD, is chief of the Adult Stem Cell Transplantation and Cellular Therapy Program at John Theurer Cancer Center, Hackensack University Medical Center. 

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How stem cells in human teeth respond to different environmental conditions offers clues for regenerative medicine.

How stem cells in human teeth respond to different environmental conditions offers clues for regenerative medicine.

By: Roni Dengler, PhD

Feb 7, 2022

When Thimios Mitsiadis was young, he wanted to be an astronaut. As he got older, he thought he would like to become a musician. Later, he considered becoming a priest. But both of his parents were in education, and the house he grew up in was full of books. Now, he too is an academic. The environment he grew up in nudged him along a particular life path.

Now as a developmental biologist at the University of Zurich, Mitsiadis leads a team of researchers who recently discovered that interactions with different environments, rather than inherent cellular differences, may drive the unique behaviors of stem cell populations in human teeth. The findings open new pathways for dental therapy, including cell-based regenerative treatments.

Beneath the hard enamel crown of teeth lie layers of deeper tissues, each with distinct primary functions and behaviors. At the tooth’s core is dental pulp, a highly vascularized and innervated tissue. Dental pulp harbors odontoblasts, cells that form the tooth’s second layer. The periodontium anchors teeth to the ridge of bone that contains the tooth sockets. This serves as the tooth’s great stabilizer, absorbing the shocks and stresses of chewing, a feat that requires constant, dynamic remodeling. Both tissues contain multipotent mesenchymal stem cells, which researchers evaluate for their potential to regenerate tissues.

Mitsiadis is particularly interested in how to recreate tissues from scratch. He plans to identify what disrupts the balance of homeostasis in pathological conditions and learn to replace the damaged or injured tissue. But to discover how to recreate these tissues, he first needs to understand how they work.

Mitsiadis’ team isolated dental pulp and periodontium from extracted wisdom teeth and profiled single-cell suspensions using RNAseq. Despite having different functions, the stem cell populations within the dental pulp and periodontium showed similar molecular signatures. For example, both tissues contained two main mesenchymal stem cell clusters, and expression levels of stem cell markers such as NOTCH3 were similar between the tissues.

What differed between the tissues was the microenvironment the stem cell populations inhabited. Fibroblasts were the most abundant cell type in the dental pulp, whereas epithelial cells dominated the periodontium, the researchers reported in iScience.1

Just as Mitsiadis’ home environment nudged him towards academia, the microenvironment appears to influence the behavior of dental stem cell populations.

Mitsiadis likened the findings to following local customs. “I’m Greek, and in Greece, maybe the regulations are not applied so much. But I work in Switzerland. I have to obey the rules. I am the same person, but I’m behaving differently,” he said.

Mitsiadis’ team isolated dental pulp and periodontium from extracted wisdom teeth and profiled single-cell suspensions using RNAseq. Despite having different functions, the stem cell populations within the dental pulp and periodontium showed similar molecular signatures. For example, both tissues contained two main mesenchymal stem cell clusters, and expression levels of stem cell markers such as NOTCH3 were similar between the tissues.

“We are very happily surprised because you have some cells that are festive, they are joyful, they like to recreate,” Mitsiadis continued. “But it depends on where the cells are… They obey the rules of the environment.”

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Stem cells: a revolution in therapeutics-recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies


Basic and clinical research accomplished during the last few years on embryonic, fetal, amniotic, umbilical cord blood, and adult stem cells has constituted a revolution in regenerative medicine and cancer therapies by providing the possibility of generating multiple therapeutically useful cell types. These new cells could be used for treating numerous genetic and degenerative disorders. Among them, age-related functional defects, hematopoietic and immune system disorders, heart failures, chronic liver injuries, diabetes, Parkinson’s and Alzheimer’s diseases, arthritis, and muscular, skin, lung, eye, and digestive disorders as well as aggressive and recurrent cancers could be successfully treated by stem cell-based therapies. This review focuses on the recent advancements in adult stem cell biology in normal and pathological conditions. We describe how these results have improved our understanding on critical and unique functions of these rare sub-populations of multipotent and undifferentiated cells with an unlimited self-renewal capacity and high plasticity. Finally, we discuss some major advances to translate the experimental models on ex vivo and in vivo expanded and/or differentiated stem cells into clinical applications for the development of novel cellular therapies aimed at repairing genetically altered or damaged tissues/organs in humans. A particular emphasis is made on the therapeutic potential of different tissue-resident adult stem cell types and their in vivo modulation for treating and curing specific pathological disorders.

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