Stem cell brain injections let people walk again after stroke

People once dependent on wheelchairs after having a stroke are walking again since receiving injections of stem cells into their brains. Participants in the small trial also saw improvements in their speech and arm movements.

“One 71-year-old woman could only move her left thumb at the start of the trial,” says Gary Steinberg, a neurosurgeon at Stanford University who performed the procedure on some of the 18 participants. “She can now walk and lift her arm above her head.”

Run by SanBio of Mountain View, California, this trial is the second to test whether stem cell injections into patients’ brains can help ease disabilities resulting from stroke. Patients in the first, carried out by UK company ReNeuron, also showed measurable reductions in disability a year after receiving their injections and beyond.

All patients in the latest trial showed improvements. Their scores on a 100-point scale for evaluating mobility – with 100 being completely mobile – improved on average by 11.4 points, a margin considered to be clinically meaningful for patients. “The most dramatic improvements were in strength, coordination, ability to walk, the ability to use hands and the ability to communicate, especially in those whose speech had been damaged by the stroke,” says Steinberg.

In both trials, improvements in patients’ mobility had plateaued since having had strokes between six months and three years previously.

“We used to think the affected brain circuits were dead,” says Steinberg. “Now, we have to rethink this, and I personally think the circuits are inhibited, and our treatment helps to disinhibit them.”

Baby steps

Steinberg injected the cells through a borehole in the skull into regions of the brain that control motor movements, and which had been damaged by the stroke. Each participant received either 2.5, 5 or 10 million cells.

The injected material consisted of mesenchymal stem cells taken from the bone marrow of two healthy donors. SanBio genetically engineered the cells to possess a gene called Notch1, which activates factors that help brain development in infants. Experiments in rats revealed that the engineered stem cells disappear within a month or so, but not before secreting several growth factors that build connections between brain cells and spawn the growth of new blood vessels to nourish growing brain tissue.

“We think the cells change the adult brain so that it’s more like a baby’s brain, which repairs very well,” says Steinberg. “They are secreting all sorts of growth factors, which aid repair, and which also alter the immune system to get rid of inflammation that otherwise obstructs repair.”

In the ReNeuron trial, patients received neural stem cells originally extracted from the brains of aborted fetuses, then multiplied to produce larger amounts.

“This is very encouraging news for the field of stem cell research and especially patients with established disability as a result of stroke, where this is no proven treatment to aid recovery,” says Julian Howell, chief medical officer at ReNeuron. “Both companies are at a similar stage of development, and while it’s great to hear stories of major improvements in some patients, controlled studies are absolutely necessary to establish the benefits and risks of stem cell therapy for stroke.”

Remarkable results

ReNeuron is preparing a second trial, while SanBio is in the process of performing the treatment on a further 156 patients. Steinberg says that this time, a third of the patients will receive a sham treatment – a hole in the head without the injection of stem cells – and the remainder will receive either 2.5 or 5-million cells.

There are around 30 similar trials in progress. These deliver stem cells to stroke patients by injecting them into the blood, but none have shown such remarkable results as the two trials that injected the cells into the brain, says Steinberg. “We still have much to learn, including the right cell for the job, the right dose and the right means of delivery,” he says.

The UK Stroke Association welcomed the results but also cautioned that further trials are essential to provide additional evidence the treatment works. “Although small, this latest trial suggests that the treatment is safe and may be able to restore movement to people previously lost after stroke,” says Shamim Quadir, a spokesman for the association. “The trial adds to a growing body of early clinical evidence suggesting stem cell treatment could promote recovery in people months, even years, after having a stroke, bringing hope to many living with a disability.”

Journal reference: Stroke, in press

Source: New Scientist (By Andy Coghlan)


What Are Mesenchymal Stem Cells?

The above images are colored scanning electron micrographs (SEM) of human Mesenchymal Stem Cells. MSCs are multipotent stromal (connective tissue) cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage cells), and adipocytes (fat cells).

Learn more about Mesenchymal Stem Cells

The youngest, most primitive MSCs can be obtained from the umbilical cord tissue, namely Wharton’s jelly and the umbilical cord blood. However the MSCs are found in much higher concentration in the Wharton’s jelly compared to the umbilical cord blood, which is a rich source of hematopoietic stem cells. The umbilical cord is easily obtained after the birth of the newborn, is normally thrown away, and poses no risk for collection. The umbilical cord MSCs have more primitive properties than other adult MSCs obtained later in life, which might make them a useful source of MSCs for clinical applications.

Adipose tissue is one of the richest sources of MSCs. There are more than 500 times more stem cells in 1 gram of fat than in 1 gram of aspirated bone marrow. Adipose stem cells are actively being researched in clinical trials for treatment of a variety of diseases. Additionally, amniotic fluid has been shown to be a rich source of stem cells. As many as 1 in 100 cells collected during amniocentesis has been shown to be a pluripotent mesenchymal stem cell.

Images above © © Steve Gschmeissner / Science Source

Herpes-loaded stem cells used to kill brain tumors

Harvard Stem Cell Institute (HSCI) scientists at Massachusetts General Hospital have a potential solution for how to more effectively kill tumor cells using cancer-killing viruses. The investigators report that trapping virus-loaded stem cells in a gel and applying them to tumors significantly improved survival in mice with glioblastoma multiforme, the most common brain tumor in human adults and also the most difficult to treat.

The work, led by Khalid Shah, MS, PhD, an HSCI Principal Faculty member, is published in the Journal of the National Cancer Institute. Shah heads the Molecular Neurotherapy and Imaging Laboratory at Massachusetts General Hospital.

Cancer-killing or oncolytic viruses have been used in numerous phase 1 and 2 clinical trials for brain tumors but with limited success. In preclinical studies, oncolytic herpes simplex viruses seemed especially promising, as they naturally infect dividing brain cells. However, the therapy hasn’t translated as well for human patients. The problem previous researchers couldn’t overcome was how to keep the herpes viruses at the tumor site long enough to work.

Shah and his team turned to mesenchymal stem cells (MSCs)—a type of stem cell that gives rise to bone marrow tissue—which have been very attractive drug delivery vehicles because they trigger a minimal immune response and can be utilized to carry oncolytic viruses. Shah and his team loaded the herpes virus into human MSCs and injected the cells into glioblastoma tumors developed in mice. Using multiple imaging markers, it was possible to watch the virus as it passed from the stem cells to the first layer of brain tumor cells and subsequently into all of the tumor cells.

“So, how do you translate this into the clinic?” asked Shah, who also is an Associate Professor at Harvard Medical School.

“We know that 70-75 percent of glioblastoma patients undergo surgery for tumor debulking, and we have previously shown that MSCs encapsulated in biocompatible gels can be used as therapeutic agents in a mouse model that mimics this debulking,” he continued. “So, we loaded MSCs with oncolytic herpes virus and encapsulated these cells in biocompatible gels and applied the gels directly onto the adjacent tissue after debulking. We then compared the efficacy of virus-loaded, encapsulated MSCs versus direct injection of the virus into the cavity of the debulked tumors.”

Using imaging proteins to watch in real time how the virus combated the cancer, Shah’s team noticed that the gel kept the stem cells alive longer, which allowed the virus to replicate and kill any residual cancer cells that were not cut out during the debulking surgery. This translated into a higher survival rate for mice that received the gel-encapsulated stem cells.

“They survived because the virus doesn’t get washed out by the cerebrospinal fluid that fills the cavity,” Shah said. “Previous studies that have injected the virus directly into the resection cavity did not follow the fate of the virus in the cavity. However, our imaging and side-by-side comparison studies showed that the naked virus rarely infects the residual tumor cells. This could give us insight into why the results from clinical trials with oncolytic viruses alone were modest.”

The study also addressed another weakness of cancer-killing viruses, which is that not all brain tumors are susceptible to the therapy. The researchers’ solution was to engineer oncolytic herpes viruses to express an additional tumor-killing agent, called TRAIL. Again, using mouse models of glioblastoma—this time created from brain tumor cells that were resistant to the herpes virus—the therapy led to increased animal survival.

“Our approach can overcome problems associated with current clinical procedures,” Shah said. “The work will have direct implications for designing clinical trials using oncolytic viruses, not only for brain tumors, but for other solid tumors.”

Further preclinical work will be needed to use the herpes-loaded stem cells for breast, lung and skin cancer tumors that metastasize to the brain. Shah predicts the approach will enter clinical trials within the next two to three years.

Home-grown Bone

Today, replacing damaged bones with ones grown in a lab is already a reality. Scientists can grow mesenchymal stem cells (MSCs) from the patient’s bone marrow on a porous ceramic scaffold, as shown in this scanning electron microscope image, and attach it to their healthy bone. However, MSCs can also turn into muscle or fat cells, so it’s vital to ensure that they turn, or differentiate, into bone cells. The ceramic scaffold plays an important role in this: like the supporting scaffold of real bone, it contains calcium which induces MSCs to differentiate into bone cells rather than muscle or fat. Researchers are studying how calcium does this, by finding out which genes were activated at various times after the MSCs were placed on the scaffold. This will help test new scaffolds, with different shapes or components, for how effective they are at helping the cells differentiate.

Written by Esther Redhouse White

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Unexpected stem cell factories found inside teeth

Researchers have now discovered nervous system cells transforming back into stem cells in a very surprising place: inside teeth. This unexpected source of stem cells potentially offers scientists a new starting point from which to grow human tissues for therapeutic or research purposes without using embryos.

“More than just applications within dentistry, this finding can have very broad implications,” says developmental biologist Igor Adameyko of the Karolinska Institute in Stockholm, who led the new work. “These stem cells could be used for regenerating cartilage and bone as well.”

Researchers were studying glial cells, which support and surround neurons that wind through the mouth and gums and help transmit signals of pain from the teeth to the brain. When they added fluorescent labels to a set of glial cells in mice, they saw that over time, some of them migrated away from neurons in the gums toward the inside of teeth, where they transformed into mesenchymal stem cells. Eventually, the same cells matured into tooth cells, the team reported this week in Nature

Flexible. Nerve cells sometimes spontaneously transform into stem cells inside teeth, researchers have discovered. Pasieka/Science Photo Library/Corbis

World’s first pelvis transplant carried out in Italy.

The Centre for Orthopaedic Trauma (CTO) in Turin, Italy, has performed the world’s first pelvis transplant, an operation that saved the life of an 18-year-old suffering from osteosarcoma. The condition was considered inoperable and the boy responded quite well to 16 cycles of chemotherapy, but the doctors didn’t stop at the traditional treatment, racking their brains to find a definitive solution.

Osteosarcoma is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma) and that exhibits osteoblastic differentiation and produces malignantosteoid. Osteosarcoma is the most common histological form of primary bone cancer and it is most prevalent in children and young adults. It tend to occur at the sites of bone growth, presumably because proliferation makes osteoblastic cells in this region prone to acquire mutations that could lead to transformation of cells (RB gene and p53 gene are commonly involved).

In an 11.5-hour operation, surgeons removed half the patient’s pelvis along with part of his hip affected by the cancer, replacing them with a prosthetic made in the United States from titanium covered in tantalum, a non-corrosive metal mainly used in electronics components.

The operation had “an excellent outcome” and the patient is now undergoing intensive therapy to help him adapt to his new pelvis, the hospital said in a statement.

(Picture by Alexey Kashpersky).

Embryonic Stem Cells Offer Treatment Promise for Multiple Sclerosis

Scientists in the University of Connecticut’s Technology Incubation Program have identified a novel approach to treating multiple sclerosis (MS) using human embryonic stem cells, offering a promising new therapy for more than 2.3 million people suffering from the debilitating disease.

The researchers demonstrated that the embryonic stem cell therapy significantly reduced MS disease severity in animal models, and offered better treatment results than stem cells derived from human adult bone marrow.

The study was led by ImStem Biotechnology Inc. of Farmington, Conn., in conjunction with UConn Health Professor Joel Pachter, Assistant Professor Stephen Crocker, and Advanced Cell Technology (ACT) Inc. of Massachusetts. ImStem was founded in 2012 by UConn doctors Xiaofang Wang and Ren-He Xu, along with Yale University doctor Xinghua Pan and investor Michael Men.

“The cutting-edge work by ImStem, our first spinoff company, demonstrates the success of Connecticut’s Stem Cell and Regenerative Medicine funding program in moving stem cells from bench to bedside,” says Professor Marc Lalande, director of the UConn’s Stem Cell Institute.

The research was supported by a $1.13 million group grant from the state of Connecticut’s Stem Cell Research Program that was awarded to ImStem and Professor Pachter’s lab.

“Connecticut’s investment in stem cells, especially human embryonic stem cells, continues to position our state as a leader in biomedical research,” says Gov. Dannel P. Malloy. “This new study moves us one step closer to a stem cell-based clinical product that could improve people’s lives.”

The researchers compared eight lines of adult bone marrow stem cells to four lines of human embryonic stem cells. All of the bone marrow-related stem cells expressed high levels of a protein molecule called a cytokine that stimulates autoimmunity and can worsen the disease. All of the human embryonic stem cell-related lines expressed little of the inflammatory cytokine.

Another advantage of human embryonic stem cells is that they can be propagated indefinitely in lab cultures and provide an unlimited source of high quality mesenchymal stem cells – the kind of stem cell needed for treatment of MS, the researchers say. This ability to reliably grow high quality mesenchymal stem cells from embryonic stem cells represents an advantage over adult bone marrow stem cells, which must be obtained from a limited supply of healthy donors and are of more variable quality.

“Groundbreaking research like this furthering opportunities for technology ventures demonstrates how the University acts as an economic engine for the state and regional economy,” says Jeff Seemann, UConn’s vice president for research.

The findings also offer potential therapy for other autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and type-1 diabetes, according to Xu, a corresponding author on the study and one of the few scientists in the world to have generated new human embryonic stem cell lines.

There is no cure for MS, a chronic neuroinflammatory disease in which the body’s immune system eats away at the protective sheath called myelin that covers the nerves. Damage to myelin interferes with communication between the brain, spinal cord, and other areas of the body. Current MS treatments only offer pain relief, and slow the progression of the disease by suppressing inflammation.

“The beauty of this new type of mesenchymal stem cells is their remarkable higher efficacy in the MS model,” says Wang, chief technology officer of ImStem.

The group’s findings appear in the current online edition of Stem Cell Reports, the official journal of the International Society for Stem Cell Research. ImStem is currently seeking FDA approval necessary to make this treatment available to patients.

Newborns a hope for spinal injuries

It all started at a symposium five years ago. Catherine Gorrie, an expert in spinal cord injury, was listening to a presentation about the differences between the developing brains of children and the mature ones of adults when she had an “aah-haa” moment.

“I began to wonder if there is something in the spines of children that could be manipulated for repair,” says Dr Gorrie, a neuroscientist at the University of Technology, Sydney (UTS). It made sense. Dr Gorrie already knew that the more adaptable, or “plastic”, spinal cords of infants responded more efficiently to injury than did those of adults.

If she could tease out the factors that encouraged generic cells, so-called stem cells, in the spines of newborns to become new nerve cells, neurones, Dr Gorrie reasoned that it should be possible to mimic the process and help repair spinal cord injuries in people of all ages. That would be incredibly important because, to date, there is no cure for spinal cord injury and no proven drug treatment.

Read more

 Nanofiber scaffolds demonstrate new features in the behavior of stem and cancer cells

A discovery in the field of biomaterials may open new frontiers in stem and cancer cell manipulation and associated advanced therapy development. Novel scaffolds are shown enabling cells to behave in a different but controlled way in vitro due to the presence of aligned, self-assembled ceramic nanofibers of an ultra-high anisotropy ratio augmented into graphene shells.

“This unique hybrid nano-network allows for an exceptional combination of selective guidance stimuli for stem cell development, variations in immune reactions, and behavior of cancer cells”, says Professor Michael Gasik from Aalto University.

These scaffolds, for example, were shown to be able to direct the preferential orientation of human mesenchymal stem cells, similarly to neurogenic lineage, to suppress of major inflammatory factors expression and to immobilize cancer cells.

The results of the study were published in Nature Scientific Reports

Caption: Fluorescent images of breast carcinoma cell line showing the morphological changes of cells grown on vertical GAIN scaffolds. Credit: Aalto University / Michael Gasik

Most heart muscle cells formed during childhood       

 New human heart muscle cells can be formed, but this mainly happens during the first ten years of life, according to a new study from Karolinska Institutet in Sweden. Other cell types, however, are replaced more quickly. The study, which is published in the journal Cell, demonstrates that the heart muscle is regenerated throughout a person’s life, supporting the idea that it is possible to stimulate the rebuilding of lost heart tissue.  

  “Our study shows that endothelial cells, mesenchymal cells and heart muscle cells are renewed in the human heart throughout life, albeit at a different rate for different cells,” says study leader Jonas Frisén from the Department of Cell and Molecular Biology. “Our findings suggest that it can be rational and realistic to develop new therapeutic strategies for strengthening the body’s own regenerative capacity to treat heart diseases."   

Publication: ‘Dynamics of cell generation and turnover in the human heart’, Olaf Bergmann, Sofia Zdunek, Anastasia Felker, Mehran Salehpour, Kanar Alkass, Samuel Bernard, Staffan Sjöström, Miros?awa Szewczykowska, Teresa Jackowska, Cris dos Remedios, Torsten Malm, Michaela Andrä, Shira Perl, John Tisdale, Ramadan Jashari,Jens R. Nyengaard, Göran Possert, Stefan Jovinge, Henrik Druid, and Jonas Frisén, publishing in Cell June 18, 2015 issue, online first 11 June  2015. 

Unlocking the Potential of Stem Cells to Repair Brain Damage

Read the full article Unlocking the Potential of Stem Cells to Repair Brain Damage at

A QUT scientist is hoping to unlock the potential of stem cells as a way of repairing neural damage to the brain.

The research is in Developmental Biology. (full access paywall)

Research: “Mesenchymal stem cells, neural lineage potential, heparan sulfate proteoglycans and the matrix” by Rachel K. Okolicsanyi, Lyn R. Griffiths, Larisa M. Haupt in Developmental Biology. doi:10.1016/j.ydbio.2014.01.024

Image: Researchers are manipulating adult stem cells from bone marrow to produce a population of cells that can be used to treat brain damage. This image shows neural stem cells and is for illustrative purposes only. Credit Joseph Elsbernd.

Researchers find new way to force stem cells to become bone cells

Imagine you have a bone fracture or a hip replacement, and you need bone to form, but you heal slowly – a common fact of life for older people. Instead of forming bone, you could form fat. Researchers at the University of North Carolina School of Medicine may have found a way to tip the scale in favor of bone formation. They used cytochalasin D, a naturally occurring substance found in mold, as a proxy to alter gene expression in the nuclei of mesenchymal stem cells to force them to become osteoblasts (bone cells).

By treating stem cells – which can become fat or bone cells - with cytochalasin D– the result was clear: the stem cells became bone cells. Further, injecting a small amount of cytochalasin D into the bone marrow space of mice caused bone to form. This research, published in the journal Stem Cells, details how the scientists altered the stem cells and triggered bone growth.

“And the bone forms quickly,” said Janet Rubin, MD, senior author of the paper and professor of medicine at the UNC School of Medicine. “The data and images are so clear; you don’t have to be a bone biologist to see what cytochalasin D does in one week in a mouse.”

Rubin added, “This was not what we expected. This was not what we were trying to do in the lab. But what we’ve found could become an amazing way to jump-start local bone formation. However, this will not address osteoporosis, which involves bone loss throughout the skeleton.”

At the center of the discovery is a protein called actin, which forms fibers that span the cytoplasm of cells to create the cell’s cytoskeleton. Osteoblasts have more cytoskeleton than do adipocytes (fat cells). Buer Sen, MD, first author of the Stem Cells paper and research associate in Rubin’s lab, used cytochalasin D to break up the actin cytoskeleton. In theory – and according to the literature – this should have destroyed the cell’s ability to become bone cells. The cells, in turn, should have been more likely to turn into adipocytes. Instead, Sen found that actin was trafficked into the nuclei of the stem cells, where it had the surprising effect of inducing the cells to become osteoblasts.

“My first reaction was, ‘No way, Buer,’” Rubin said. “'This must be wrong. It goes against everything in the literature.’ But he said, 'I’ve rerun the experiments. This is what happens.’”

Rubin’s team expanded the experiments while exploring the role of actin. They found that when actin enters and stays in the nucleus, it enhances gene expression in a way that causes the cell to become an osteoblast.

“Amazingly, we found that the actin forms an architecture inside the nucleus and turns on the bone-making genetic program,” Rubin said. “If we destroy the cytoskeleton but do not allow the actin to enter the nucleus, the little bits of actin just sit in the cytoplasm, and the stem cells do not becomebone cells.”

Rubin’s team then turned to a mouse model. Using live mice, they showed that cytochalasin D induced bone formation in mice.

Bone formation in mice isn’t very different from that in humans, so this research might be translatable. And while cytochalasin D might not be the actual agent scientists use to trigger bone formation in the clinic, Rubin’s study shows that triggering actin transport into the nuclei of cells may be a good way to force mesenchymal stem cells to become bone cells.

22 January 2015

Reversing Diabetes

Diabetes is often linked to obesity but about one in 10 cases is caused by the immune system destroying insulin-making cells in the pancreas. An important step towards preventing this disease, called type 1 diabetes, has been taken by scientists experimenting with mesenchymal stem cells, pictured, which are known to have powerful immune-suppressing effects. In mice prone to type 1 diabetes, these stem cells were engineered to create an adhesive surface molecule – also found on some other cell types – that sticks to inflamed tissue. When the mice began to develop diabetes, the modified stem cells lodged in the swollen islets, or cell clusters, inside the pancreas, protecting them from further damage from the immune system and reversing the onset of the disease. However, much more research will be needed before this type of treatment can be considered for humans.

Written by Mick Warwicker

Image by Steve Gschmeissner
Science Photo Library
Any re-use of this image must be authorised by Science Photo Library
Research published in Stem Cells, December 2014

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Medical researchers were surprised when they discovered a new way to turn stem cells into bone cells—and ultimately trigger bone growth in mice.

The team expected the stem cells to become fat cells.

“This was not what we expected. This was not what we were trying to do in the lab. But what we’ve found could become an amazing way to jump-start local bone formation,” says Janet Rubin, a professor of medicine at the UNC School of Medicine.

Rubin and colleagues used cytochalasin D, a naturally occurring substance found in mold, as a proxy to alter gene expression in the nuclei of mesenchymal stem cells to force them to become osteoblasts (bone cells).

Read more

Funding:  The National Institutes of Health funded the research.

Baby Tooth 👶

A tooth developing withing the mandible of an embryo. This tooth will eventually erupt when its owner is 6 months of age.


She’s waving!


Tooth development is an amazing feat of embryological engineering.

Your baby teeth start to develop when the embryo reaches 44 days old. They begin as a down-growth of the epithelial cells (the dental lamina) that line the inside of your embryonic mouth, with each lamina set to become its own baby tooth.

As the dental lamina grows it forms a ‘bud’ shaped structure surrounded by mesenchymal (mesoderm derived) cells that form the dental follicle.

As the epithelial bud grows it enters the ‘cap’ stage where it becomes more bean shaped and is referred to as the enamal organ. The mesenchymal cells below the belly button of the bean shaped enamel organ condense to form the dental papilla. The whole developing structure is still surrounded by the dental follicle.

As the tooth grows further it begins to take the shape of a ‘bell‘. The baby tooth shown here is a bell stage tooth. The enamel organ (pale hair) surrounds the dental papilla (face) and looks like it its molding the papilla into the shape of the future pointy tooth crown. The dental follicle still surrounds these growing structures.

These 3 structures (enamel organ, papilla and follicle) are all that is needed to grow a normal tooth:

  • Cells of the enamel organ differentiate to form ameloblasts that will secrete enamel.
  • Cells of the dental papilla form the dental pulp and, around its periphery, they differentiate into special odontoblasts that will secrete dentin all around the pulp chamber.
  • Cells of the dental follicle form the structures of the periodontium (tissues that surround the tooth root and anchor it to the surrounding bone) by differentiating into cementoblasts that secrete cementum and fibroblasts that form the periodontal ligament.

This entire event is co-ordinated by a series of events known as inductive interaction - where the development and secretions of one cell type are required to trigger the differentiation and secretion of another cell type until all the tissues are secreted in the appropriate locations.

How an Anti-Cancer Treatment Might Actually Fuel Cancer Metastasis

In recent years, a biological process called epithelial-mesenchymal transition (EMT) has been implicated in the ability of cancer stem cells to flourish and spread. EMT naturally occurs during embryogenesis when cells migrate and then grow into new organs during early development. EMT endows cancer cells with the necessary plasticity to create cancer stem cells (CSCs)  – self-sustaining and self-renewing sources of malignancy that contribute to the metastatic cascade.

Metastasis – or the spread of cancer from a primary tumor to other locations elsewhere in the body – is responsible for 90 percent of cancer-related deaths. Not surprisingly, blocking EMT in cancer progression is a major therapeutic goal.

The cirmtuzumab clinical trial, headed by Thomas Kipps, MD, is one example. Cirmtuzumab is an experimental monoclonal antibody treatment that targets ROR1, a protein used by embryonic cells during early development and exploited by chronic lymphocytic leukemia cancer cells.

But while there is substantial support for the role of EMT in driving metastasis, the actual molecular mechanisms that govern formation of CSCs is much more of a mystery. In a new paper, published this week in Oncotarget, John T. Chang, MD, and colleagues shed light on this mystery. They discovered that inhibition of selective proteasomes (protein complexes inside cells whose main function is to degrade unneeded or damaged proteins) enables mammary epithelial cells to acquire the characteristics of cancer stem cells.

The findings have obvious clinical import: An emerging cancer treatment is the use of proteasome inhibitors, which block pathways critical to tumor cell growth and survival. The new paper suggests a possible mechanism used by carcinoma cells to escape proteasome inhibitor-based therapy and highlights the potential risk.

Liver tissue bioprinted from stem cells

The 3-D-printed parts of the biomimetic liver tissue include: liver cells derived from human induced pluripotent stem cells (left), endothelial and mesenchymal supporing cells (center), and the resulting organized combination of multiple cell types (right). — Chen Laboratory, UC San Diego

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