Stem Cell Research

At Long Last A Method Is Developed to Expand Blood Stem Cells for Bone Marrow Transplant

An expansion of healthy HSCs in the lab would mean that fewer stem cells need to be retrieved from donors. It also suggests that adult blood stem cells could be frozen and banked for future expansion and use — which is not currently possible.

New research has engineered a protein to amplify adult HSCs once they were extracted from the bone marrow of a donor. The engineered protein maintains the expanded HSCs in a stem-like state — meaning, they will not differentiate into specialized blood cell types before they are transplanted in the recipient's bone marrow.

"Our work demonstrates that we can overcome a major technical hurdle in the expansion of adult blood stem cells, making it possible, for the first time, to produce them on an industrial scale,"  said Dr. Pengbo Zhou, professor of pathology and laboratory medicine at Weill Cornell Medical College.

Adapted from the Weill Cornell Medical College announcement. Read further here.

Discovery in Bone Marrow May Improve Chemotherapy, Stem Cell Transplants

The new findings, in mice, suggest that it may be possible to therapeutically target support cells in a particular niche. On the one hand, a drug that nourishes support cells could encourage blood stem cells to establish themselves in the bone marrow, enabling patients who have had stem cell transplants to more quickly rebuild their immune systems.

“Our results offer hope for targeting these niches to treat specific cancers or to improve the success of stem cell transplants,” says senior author Daniel Link, MD, Professor of Medicine at Washington University in St. Louis. “Already, we and others are leading clinical trials to evaluate whether it is possible to disrupt these niches in patients with leukemia or multiple myeloma.”

Working in the mice, the researchers selectively deleted a critical gene, CXCL12, which is known to be important for keeping blood stem cells healthy. Rather than knock out the gene in all of the support cells in a niche, the researchers deleted the gene in specific types of support cells. This led to the discovery that each niche holds only certain blood stem cells that are nourished by a unique set of support cells.

Adapted from the University of Washington in St. Louis announcement. Read further here.

Related post.

Mechanism That Maintains Stem Cell Readiness Identified

 An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow according to new research. The family of proteins investigated in the research could help open a new field of biology integrating immunology with stem cell and cancer research.

“Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers,” said Dr. Chengcheng “Alec” Zhang, assistant professor in UT Southwestern’s departments of physiology and developmental biology. “Our research identified a protein receptor on cancer cells called a classical immune inhibitory receptor that inhibits differentiation. Knowing the identity of this protein should facilitate the development of new drugs to treat cancers.”

Researchers Discover 'Altruistic' Stem Cell Behavior With Possible Link To Cancer

New research has shown that certain human embryonic stem cells, in times of stress, produce molecules that not only benefit themselves, but also help nearby cells survive.

When most groups of mammalian cells are faced with a shortage of nutrients or oxygen, the phrase “every man for himself” is more apt than “all for one, one for all.” Unlike colonies of bacteria, which often cooperate to thrive as a group, mammalian cells have never been observed to help one another out. 

While altruism is generally thought of as a virtue, it can have a downside for hESCs: The altruistic cells appear to be more prone to accumulating mutations, a sign that they could lead to cancers. A better understanding of hESC altruism could provide new insights into cancer therapies, as well as improving scientists’ ability to develop safe and effective stem cell treatments for other diseases.

“Altruism has been reported among bacterial populations and among humans and other animals, like monkeys and elephants,” said Stanford University postdoctoral scholar Bikul Das, MBBS, PhD. “But in mammalian cells — at the cellular level — the idea of altruism has never been described before.”

Video: Drug Discovered That Destroys Human Cancer Stem Cells But Not Healthy Ones

The drug thioridazine apparently kills cancer stem cells in humans while avoiding the toxic side-effects of conventional cancer treatments.

"The unusual aspect of our finding is the way this human-ready drug actually kills cancer stem cells by changing them into cells that are non-cancerous," said Mick Bhatia, scientific director of McMaster University's Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine.

Unlike chemotherapy and radiation, thioridazine appears to have no effect on normal stem cells. The research team has identified another dozen drugs that have good potential for the same response.

 

Arsenic Spurs Tumor Growth By Turning Stem Cells Cancerous

That normal cells become cancerous when they are treated with inorganic arsenic has been previously determined by this same group of researchers. Their new research shows that when these cancer cells are placed close to -- but not in contact with -- normal stem cells, the normal stem cells very rapidly acquire the characteristics of cancer stem cells, demonstrating that malignant cells are able to send molecular signals through a semi-permeable membrane, where cells can't normally pass, and turn the normal stem cells into cancer stem cells.

"This paper shows a different and unique way that cancers can expand by recruiting nearby normal stem cells and creating an overabundance of cancer stem cells," said Michael Waalkes, Ph.D., Group Leader at the National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, part of NIH.

Overabundance Of A Particular Protein Expands Breast Cancer Stem Cells

An essential protein for normal stem cell renewal also promotes the growth of breast cancer stem cells when it's overproduced in those cells. Researchers have also discovered that two drugs block the cascade of molecular events, thwarting formation of breast tumor-initiating cells.

"Overexpression of the EZH2 protein has been linked to breast cancer progression, but the molecular details of that connection were unknown," said Mien-Chie Hung, Ph.D., professor and chair of MD Anderson's Department of Molecular and Cellular Oncology.

"Tumor-initiating cancer cells that arise from the primary cancer stem cells also are thought to drive cancer progression," Hung said. "Our research connects EZH2 to the growth of breast tumor-initiating cells."

Stem cell Discovery Could Lead To Improved Bone Marrow Transplants

Researchers have identified a key molecule for holding blood stem cells in their niche within the bone marrow.

Bone marrow transplants are a type of stem cell therapy used to treat cancers such as lymphoma and leukemia and other blood-related diseases. In a bone marrow transplant the "active ingredients" are hematopoietic stem cells which live in the bone marrow and give rise to all the different kinds of mature blood cells. The new study shows that hematopoietic stem cells use a molecule called Robo4 to anchor themselves in the bone marrow.

"Robo4 is a rare molecule that is found only in hematopoietic stem cells and in the endothelial cells of blood vessels," said Camilla Forsberg, assistant professor of biomolecular engineering in the Baskin School of Engineering at UC Santa Cruz. After earlier work in her lab showed that Robo4 is specific for hematopoietic stem cells, Forsberg set out to discover how it functions.

Turns out that Robo4 acts as an adhesion molecule, interacting with other components of the bone marrow to bind the stem cells into their proper niche. Forsberg's lab is trying to find out what molecules bind to Robo4, which could lead to a better understanding of that niche. While other types of stem cells are routinely grown in petri dishes, hematopoietic stem cells are very difficult to grow in the lab. They seem to require the bone marrow environment to function properly, and Forsberg's research might enable researchers to recreate that environment in a petri dish.

Other molecules besides Robo4 are also known to be involved in guiding the localization of hematopoietic stem cells in the bone marrow. Forsberg's results indicate that one of these, called Cxcr4, acts together with Robo4 to retain hematopoietic stem cells in the bone marrow. But the two molecules appear to act through different molecular mechanisms. Inhibition of both molecules may be the best way to achieve efficient mobilization of hematopoietic stem cells suggested Forsberg.

The discovery that the cells need Robo4 to stay in the bone marrow has potential therapeutic implications. An increasingly common alternative to traditional bone marrow transplants (which require anesthesia for the bone marrow extraction) involves harvesting hematopoietic stem cells from the blood. Repeated injections of drugs are needed to get the stem cells to leave the bone marrow and enter the bloodstream so that they can be collected with a blood draw. A drug that blocks Robo4 could be a safer and more effective way to do this.

Adapted from the University of California Santa Cruz announcement.

To Function, Brain Stem Cells May Rely On A Specific Molecule

The "cradle" of new neurons in the adult brain is the subventricular zone, a tissue structure lining the lateral ventricles. This is where neural or brain stem cells reside, the cells responsible for generating new neurons if needed.

For many years now, the subventricular zone has been suspected to be the origin of specific malignant brain tumors called gliomas, the most deadly type of which is glioblastoma. Now researchers have shown that brain stem cells in the subventricular zone are characterized by a specific molecule: Protein Tlx, a transcription factor, which stimulates the activity of various genes. In adult mice Tlx is expressed exclusively in brain stem cells. When the scientists switched off Tlx, there were no more detectable stem cells in the brain and the formation of new neurons ceased. Functioning of the stem cells thus appears to depend on the presence of this protein.

Expanding The Arena For Potential Stem Cell Therapy: Endothial Cells Found To Dramatically Improve Capacity To Manufacture Large Quantities Of Adult Blood Stem Cells

In findings that offer the potential for new approaches to stem cell therapy, endothelial cells, the building blocks of the vascular system, have been found to keep blood stem cells dividing healthily in a lab dish much longer and more effectively than previous methods of growing the cells.

Stem cells grown in the new system could be used for bone marrow transplants that might allow lifetime repopulation of needed blood cells. The newly developed research platform might also be useful for generating and studying other types of adult stem cells since previous research has shown that other organ-specific stem cells typically reside near endothelial cells.

There are few naturally occurring stem cells in adult organs, so using them for organ regeneration is impractical. Adult stem cells can be grown in the laboratory, but until now, strategies to expand these cultures, which invariably used animal-based growth factors, serum, and genetically manipulated feeder cells, have not sustained the stem cells’ ability to self-renew for more than a few days.

In a new study, a team led by Shahin Rafii -- a Howard Hughes Medical Institute investigator at Weill Cornell Medical College in New York City -- employed endothelial cells to propagate stem cells in the laboratory without added growth factors or serum. In the body, these endothelial cells establish a “vascular niche” that is essential for regenerating blood stem cells in the adult bone marrow.

Rafii predicts that as researchers identify other factors with which endothelial cells influence stem cell behavior, this will establish a new arena in stem cell biology: “We will be able to selectively activate endothelial cells not only to induce organ regeneration, but also to inhibit the production of specific endothelial cell-derived factors in order to block tumor growth,” he says. “Our findings highlight the potential of vascular cells for generating sufficient stem cells for therapeutic organ regeneration, tumor targeting, and gene therapy applications.”

Study Gains New Insight Into Stem Cell Regenerative Process And Organism Death

Stem Cell Regenerative Medicine is the controlled differentiation of stem cells into the functionally defined cells required to mend or replace sick or damaged tissue or organs.  Our bodies do this naturally, generating rather than regenerating a complete body from a single cell, growing and maintaining the body during our early years, maintaining it during adulthood, and then somehow allowing the process to deteriorate as the body ages and finally dies.

Shedding some new light on the process of aging and death, It turns out that the loss of two proteins,  the tumor-suppressor protein p53 and the DNA-maintenance protein ATR, results in tissues deteriorating rapidly generally resulting in death.

Essentially, argued senior author Eric Brown, PhD, Assistant Professor of Cancer Biology at the University of Pennsylvania School of Medicine, the findings highlight the fact that day-to-day maintenance required to keep proliferative tissues like skin and intestines functional is about more than just regeneration, the stem cell-based process that forms the basis of tissue renewal. It's also about housekeeping, the clearing away of damaged cells.

A Salute To Joanne Kurtzberg And The Duke University Division of Blood & Bone Marrow Stem Cell Transplantation

For the most part, stem cell research is still directed at finding basic understanding. Clinical trials continue to attempt to establish safety first and efficacy second. Meanwhile, Dr. Joanne Kurtzberg at Duke University is a standout medical scientist providing real solutions pioneered through the use of unrelated donor umbilical cord blood stem cells in patients who do not have a fully matched donor.  Her efforts and creativity have extended this life-saving therapy to many patients, most of them small children.

Under Kurtzberg's direction the program has performed over 1,400 autologous and allogeneic stem cell transplants in children with cancer or genetic diseases since 1990.

Hematopoietic stem cell transplant is provided as a treatment option for a variety of acquired and congenital disorders of children and young adults including hematopoietic malignancies and solid tumors including neuroblastoma and brain tumors, inherited immune deficiency syndromes, bone marrow failure syndromes, hemoglobinopathies, and inherited metabolic diseases.

Fate Therapeutics: A Further Look At Academic Stem Cell Researchers And The Private Sector That Will Market Their Results

Academic stem cell research pioneer entree into the world of markets and profit is always a trend worth watching. Today we're taking a quick look at Fate Therapeutics.

Among our Sector Companies, all of which are publicly traded, typically someone has suggested a possibility that business people see as a probability.  From there the emphasis is on obtaining approvals from public agencies, gaining market position, branding, and developing scalability, all toward the end of profitable sales. 

Examples range from companies that raise and spend public investor money primarily on research and development (such as Advanced Cell Technologies, Geron, Osiris and others) to those companies formed to market an already existing product or discovery (Neostem comes to mind here; the company has signed numerous partnership and license agreements, particularly in foreign markets, but has yet to spend money on research).

As research into regenerative medicine and stem cells progresses, capital will continue to seek knowledge, or vice versa, and new companies will enter the potential market place.  Academic researchers will be involved through actual participation in the formation and ongoing policy of the new entity or in an advisory capacity that most probably includes an ownership interest. 

Reflections On The Recently Reported Russian Nueral Stem Cell Tumor Case

In May 2001 at the age of 9 years, again in March 2002 and once more in July 2004 at the age of 12 years, a boy was taken by his parents to be treated in a Moscow hospital with a procedure involving a transplant of fetal stem cells into his brain. 

The boy suffers from a neurodegenerative hereditary disorder, ataxia telangiectasia (AT). AT is a childhood disease that causes degeneration of  those parts of the brain controlling muscle movements and speech. As a result of headaches an MRI was performed in an Israeli hospital in 2005 and a multifocal tumor was found in the boy's brain. Subsequent analysis proved the tumor could not have been generated by the boy's own cells and therefore had to originate with the transplanted stem cells. The following is from the story in TheScientist.com.

Cancer Stem Cells May Not Respond To Standard Cancer Treatments

All cancer cells were once thought to be equal, but recent research suggests otherwise. A growing body of evidence indicates that only certain cancer cells are capable of generating and maintaining a tumor. Dubbed cancer stem cells, they can divide indefinitely to perpetuate the cancer over time. They may also be the reason why some therapies fail to wipe out a cancer entirely: cancer stem cells seem to be particularly resistant to standard cancer treatments and can remain behind like the roots of a weed.

Time Of Day Influences Blood Stem Cell Collection Yield

When it comes to collecting human stem cells for clinical transplantation, picking the right time of day to harvest cells may result in a greater yield according to a new study.

An examination of healthy donors who were contributing HSCs for bone marrow transplantation at Mount Sinai Medical Center between the years of 2000 and 2006 revealed that the average yield was greater for those who underwent the procedure in the afternoon compared with those who were harvested in the morning.

Researchers at Mount Sinai School of Medicine were interested in examining whether circadian time continues to influence mobilization of hematopoietic stem cells (HSCs) when mice are treated with granulocyte-colony-stimulating factor (G-CSF), the most common stem cell mobilizer used in the clinic. The researchers found that after stimulation with G-CSF, synchronization of blood collection with the peak circadian time produced greater HSC recovery. Therefore, even when pharmacological manipulation is used to stimulate HSC mobilization, circadian clock genes continue to influence yield.

Adapted from the Mount Sinai School of Medicine announcement through EurekAlert.

A Cure For Cancer? The University of Oklahoma Thinks So

Apparently there is exists a particular protein that only appears in stem cells. Until now, researchers knew of proteins that appeared in both regular cancer cells and stem cells, but none that was unique to stem cells. Finding one that that is could provide a cure for cancer.

Focusing on adult cancer stem cells (adult stem cells work as essential building blocks in organs by replenishing dying cells and regenerating damaged tissues) because of the major role they play in the start, growth, spread and return of cancer, the University of Oklahoma team, led by by Courtney Houchen, M.D., and Shrikant Anant, Ph.D., has already begun work to target the protein with a new compound that, once developed, would kill the stem cells and kill the cancer. By targeting the stem cells, scientists and physicians also would be able to stop the cancer from returning.

Overcoming Obstacles In Cord Blood Stem Cell Transplants

Bone marrow stem cell transplants represent the broadest and longest used form of stem cell regenerative therapy.  Various blood cancers (including myeloma, lymphoma and leukemia) have been treated since the seventies by destroying a patient's immune system with radiation and chemotherapy and then replacing it with a regenerated immune system initiated through the transplanting of bone marrow stem cells.

Bone marrow stem cells are available in cord blood (collected from the umbilical cord after the baby is delivered and separated from the cord). One of the fastest growing segments of industry generated by stem cell research is in companies that collect and cryogenically preserve cord blood and those that produce the equipment used to do it.

Cord blood is increasingly being used by transplant centers as an alternative source of stem cells for the treatment of blood cancers. Cord blood stem cells have a greater proliferative capacity than adult bone marrow stem cells and a greater number of stem cells are found in cord blood than in adult bone marrow or peripheral blood. Promising uses of cord blood stem cells outside the cancer arena are currently being researched. But right now these stem cells are most commonly used for bone marrow transplantation when a donor from a patient’s family or an unrelated donor does not produce an appropriate bone marrow match.

Cancer: Research Closes Bad But Well Traveled Road

    A lot of research and more than a few researchers have assumed that tumor angiogenesis (angiogenesis is a big word for the physiological process of growing new blood vessels from pre-existing ones) and cancer growth depend on circulating endothelial precursor cells (endothelial cells are the cells that make up the lining of blood vessels.  Endothelial precursor suggests a stem cell that has 'decided' to become a cell that makes up the lining of blood vessels). And apparently their assumptions have been wrong.

Cancer: Cell to Cell Communication, Answer To Stopping Tumor Growth?

  This recent finding suggests that there is a difference between normal stem cells and cancer stem cells that can be exploited and that Notch inhibition might be successfully used to target tumor stem cells in humans.

   In a new 30 patient, metastatic breast-cancer trial getting under way at University of Michigan and two other locations, so-called Notch inhibitors will be used to attack the small percentage of tumor cells that are stem cells.  Notch signaling pathways send signals from a cell's surface membrane into its nucleus.  Such communication activates genes that instruct the cell to make proteins that perform various tasks.  The idea of inhibiting notch communications to stop the stem cells from expanding a tumor raised a concern that normal blood-forming stem cells would be inhibited as well.  Reproduction of various blood stem cells is responsible for the recreation of literally billions of new, very necessary cells in each of us every day.