Stem Cell Clinic

Identifying the source of stem cells

By Stem Cell Medicine

7 hours ago Amy Ralston, MSU biochemist and molecular biologist, has identified a possible source of stem cells, which can advance regenerative and fertility research. Credit: G.L. Kohuth

When most animals begin life, cells immediately begin accepting assignments to become a head, tail or a vital organ. However, mammals, including humans, are special. The cells of mammalian embryos get to make a different first choice to become the protective placenta or to commit to forming the baby.

It's during this critical first step that research from Michigan State University has revealed key discoveries. The results, published in the current issue of PLOS Genetics, provide insights into where stem cells come from, and could advance research in regenerative medicine. And since these events occur during the first four or five days of human pregnancy, the stage in which the highest percentage of pregnancies are lost, the study also has significant implications for fertility research.

Pluripotent stem cells can become any cell in the body and can be created in two ways. First, they can be produced when scientists reprogram mature adult cells. Second, they are created by embryos during this crucial four-day window of a mammalian pregnancy. In fact, this window is uniquely mammalian, said Amy Ralston, MSU assistant professor of biochemistry and molecular biology, and lead author on the study.

"Embryos make pluripotent stem cells with 100 percent efficiency," she said. "The process of reprogramming cells, manipulating our own cells to become stem cells, is merely 1 percent efficient. Embryos have it figured out, and we need to learn how they're doing it."

The researchers' first discovery is that in mouse embryos, the gene, Sox2, appears to be acting ahead of other genes traditionally identified as playing crucial roles in stem cell formation. Simply put, this gene could determine the source of stem cells in mammals. Now researchers are trying to decipher why Sox2 is taking the lead role.

"Now we know Sox2 is the first indicator that a cell is pluripotent," Ralston said. "In fact, Sox2 may be the pre-pluripotent gene. We show that Sox2 is detectable in just one or two cells of the embryo earlier than previously thought, and earlier than other known stem cell genes."

The second discovery is that Sox2 has broader influence than initially thought. The gene appears to help coordinate the cells that make the fetus and the other cells that establish the pregnancy and nurture the fetus.

Future research will focus on studying exactly why Sox2 is playing this role. The team has strong insights, but they want to go deeper, Ralston said.

"Reprogramming is amazing, but it's inefficient," she said. "What we've learned from the embryo is how to improve efficiency, a process that could someday lead to generating stem cells for clinical purposes with a much higher success rate."

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Identifying the source of stem cells

UCLA Gene Discovery Shows How Stem Cells Can Be Activated to Help Immune System Respond to Infection

By Stem Cell Medical Center

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Newswise In a study led by Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research member Dr. Julian Martinez-Agosto, UCLA scientists have shown that two genes not previously known to be involved with the immune system play a crucial role in how progenitor stem cells are activated to fight infection. This discovery lays the groundwork for a better understanding of the role progenitor cells can play in immune system response and could lead to the development of more effective therapies for a wide range of diseases.

The two-year study was published online October 30, 2014 ahead of print in the journal Current Biology.

Progenitor cells are the link between stem cells and fully differentiated cells of the blood system, tissues and organs. This maturation process, known as differentiation, is determined in part by the original environment that the progenitor cell came from, called the niche. Many of these progenitors are maintained in a quiescent state or "standby mode" and are ready to differentiate in response to immune challenges (such as stress, infection or disease).

Dr. Gabriel Ferguson, a postdoctoral fellow in the lab of Dr. Martinez-Agosto and first author of the study, built upon the lab's previous research that utilized the blood system of the fruit fly species Drosophila, showing that a specific set of signals must be received by progenitor cells to activate their differentiation into cells that can work to fight infection after injury. Dr. Ferguson focused on two genes previously identified in stem cells but not in the blood system, named Yorkie and Scalloped, and discovered that they are required in a newly characterized cell type called a lineage specifying cell. These cells then essentially work as a switch, sending the required signal to progenitor cells.

The researchers further discovered that when the progenitor cells did not receive the required signal, the fly would not make the mature cells required to fight infection. This indicates that the ability of the blood system to fight outside infection and other pathogens is directly related to the signals sent by this new cell type.

"The beauty of this study is that we now have a system in which we can investigate how a signaling cell uses these two genes Yorkie and Scalloped, which have never before been shown in blood, to direct specific cells to be made," said Dr. Martinez-Agosto, associate professor of human genetics. "It can help us to eventually answer the question of how our body knows how to make specific cell types that can fight infection."

Drs. Martinez-Agosto and Ferguson and colleagues next hope that future studies will examine these genes beyond Drosophila and extend to mammalian models, and that the system will be used by the research community to study the role of the genes Yorkie and Scalloped in different niche environments.

"At a biochemical level, there is a lot of commonality between the molecular machinery in Drosophila and that in mice and humans," said Dr. Ferguson. "This study can further our shared understanding of how the microenvironment can regulate the differentiation and fate of a progenitor or stem cell."

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UCLA Gene Discovery Shows How Stem Cells Can Be Activated to Help Immune System Respond to Infection

New Valley Medical program collects umbilical cord blood

By Stem Cell Medical Center

UW Medicine/Valley Medical Center and Puget Sound Blood Center (PSBC) have joined together in a program to collect umbilical cord blood from new mothers who have just given birth. Cord blood is an important source of stem cells that can be used in lifesaving cancer treatment and research.

At the birth center here at Valley Medical Center, we have always been dedicated to providing comprehensive, high quality healthcare for the community we serve, said Judy Roudebush, vice president of Womens and Childrens Services at Valley Medical Center, in a press release. This new partnership between Valley and PSBC will help us to continue to expand care options for our community.

Cord blood is the blood remaining in the umbilical cord and placenta after the birth of a baby. Once considered a waste product that was discarded, umbilical cord blood is now known to be rich in life-saving hematopoietic stem cells the parent cells of all blood cells. About 150 milliliters of cord blood can be collected from each placenta and umbilical cord.

This program provides new moms with an opportunity to save lives at the same time they are bringing a new life into the world, remarked Donna Russell, principal at Donna Russell Consulting, LLC and Cchair of the Valley Medical Center Board of Trustees.

Cord blood collection is a painless procedure that does not interfere with the birth, or with mother-and-child bonding following delivery. There is no risk to either the mother or baby, and no cost associated with the donation. Families interested in donating cord blood at Valley Medical Center have several options for enrollment, depending on the babys due date.

We welcome this opportunity to partner with healthcare providers at Valley Medical Center to introduce a new on-site cord blood collection program, said Dr. James P. AuBuchon, president and CEO of PSBC. Cord blood is an important source for stem cell transplants that can be used to treat patients with leukemia, lymphoma and some metabolic or immune system disorders.

Families interested in donating cord blood should speak to their healthcare providers about how to make arrangements.

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New Valley Medical program collects umbilical cord blood

Human Stomach Made in the Lab Using Stem Cells

By Stem Cell Medical Center

Using pluripotent stem cells researchers have been able to build a mini stomach in the lab.REUTERS

In a first, a miniature stomach was created in the lab by scientists using stem cells.

Pluripotent stem cells that can grow into any cell type were used by scientists at Cincinnati Children's Hospital Medical Center to generate the artificial stomach.

The scientists identified the steps in stomach formation in the human embryo and by manipulating these in a petri dishwere able to coax the stem cells to form a mini stomachmeasuring 3 mm in diameter.

They then studied how h.pylori bacteria affected stomach tissues and spread rapidly. The bacteria is responsible for peptic ulcer and stomach cancer.

This first-time molecular generation of a 3D human stomach (called gastric organoid) presents new opportunities for drug discovery, modelling early stages of stomach cancer and studying some of the underpinnings of obesity related diabetes, according to Jim Wells, PhD, principal investigator and a scientist in the divisions of Developmental Biology and Endocrinology at Cincinnati Children's.

The work was conducted in collaboration with researchers at the University of Cincinnati College of Medicine.

The discovery of how to promote formation of three-dimensional gastric tissue with complex architecture and cellular composition is important as mouse models are sometimes not the best fit when studying human ailments, the team said.

The human gastric organoids will be useful to identify biochemical processes in the gut that allow gastric-bypass patients to become diabetes-free soon after surgery before losing significant weight.

Obesity fuelled diabetes and metabolic syndrome are public health challenges, addressing which has been difficult due to lack of reliable laboratory modelling systems.

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Human Stomach Made in the Lab Using Stem Cells

First human stomach tissue grown in lab

By Stem Cell Medical Center

US researchers generated functional, three-dimensional human stomach tissue to create miniature stomachs using pluripotent stem cells in a laboratory.

Human pluripotent stem cells can transform into any cell type in the body.

"Until this study, no one had generated gastric cells from human pluripotent stem cells (hPSCs)," said Jim Wells, principal investigator and a scientist at Cincinnati Children's Hospital Medical Center.

"In addition, we discovered how to promote formation of three-dimensional gastric tissue with complex architecture and cellular composition," Wells added.

"This first-time molecular generation of 3D human gastric organoids (hGOs) presents new opportunities for drug discovery, modelling early stages of stomach cancer and studying some of the underpinnings of obesity related diabetes," Wells said.

Differences between species in the embryonic development and architecture of the adult stomach make mouse models less than optimal for studying human stomach development and disease, Wells pointed out.

The key to growing human gastric organoids was to identify the steps involved in normal stomach formation during embryonic development.

By manipulating these normal processes in a petri dish, the scientists were able to coax pluripotent stem cells into becoming stomach cells.

Over the course of a month, these steps resulted in the formation of 3D human gastric organoids that were about 3 mm (1/10th of an inch) in diameter.

The study appeared in the journal Nature.

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First human stomach tissue grown in lab

Seminar on Regenerative Medicine Open to Public

By Stem Cell Clinic

JACKSON, Tenn. (PRWEB) October 30, 2014

Dr. Roy Schmidt and the staff of the Pain Specialist Center will host a free seminar and question-and-answer session about regenerative medicine on Tuesday, Nov. 11 at 6 p.m. Held at the clinic at 15 Stonebridge Blvd. in Jackson, the hour-long event will allow attendees to ask questions about stem cell therapy and platelet rich plasma therapy in a relaxed atmosphere. Guests also will have the chance to talk to individuals who have received regenerative medicine treatments, which focus on helping patients relieve pain by supporting the healing process.

Stem cell therapy focuses on delivering the patients own stem cells to parts of the body that are in need. After adipose tissue (comprised of fat cells) is taken from the patients body, it is made into a stem cell concentrate. That concentrate is injected at the focal point of pain or area that needs healing. Schmidt, who is certified to administer stem cell therapy, was trained by Bioheart Chief Scientific Officer Kristin Comella. Comella has been recognized as a national leader in stem cell therapy.

Platelet rich plasma (PRP) or platelet concentrates have been studied extensively since the 1990s. While similar products previously used in medicine (fibrin glue) were very expensive, PRP provides a cost-effective alternative. Plasma concentrates seek to help the body continue the healing process and strengthen the weakened tissue. It is often used for tendon problems, in addition to issues with ligaments, muscles, meniscus, cartilage, bone, wound and intervertebral discs. The supplemental role of hyperbaric oxygen therapy will be discussed at the event, also.

A board certified anesthesiologist, Schmidt has practiced pain management in the Jackson area for two decades. The Pain Specialist Center provides consultation and pain management services to patients suffering from chronic pain syndromes and terminal cancer pain. Individuals can learn more by going online to http://beyondpills.com, http://nopainmd.com and http://hyperbaricoxygentherapies.com, calling 731-660-2056 or e-mailing info(at)beyondpills(dot)com. Event information is on Facebook at http://www.facebook.com/PainSpecialistCenter.

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Seminar on Regenerative Medicine Open to Public

Mechanism that allows differentiated cell to reactivate as a stem cell revealed

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One kind of stem cell, those referred to as 'facultative', form part -- together with other cells -- of tissues and organs. There is apparently nothing that differentiates these cells from the others. However, they have a very special characteristic, namely they retain the capacity to become stem cells again. This phenomenon is something that happens in the liver, an organ that hosts cells that stimulate tissue growth, thus allowing the regeneration of the organ in the case of a transplant. Knowledge of the underlying mechanism that allows these cells to retain this capacity is a key issue in regenerative medicine.

Headed by Jordi Casanova, research professor at the Instituto de Biologa Molecular de Barcelona (IBMB) of the CSIC and at IRB Barcelona, and by Xavier Franch-Marro, CSIC tenured scientist at the Instituto de Biologa Evolutiva (CSIC-UPF), a study published in the journal Cell Reports reveals a mechanism that could explain this capacity. Working with larval tracheal cells of Drosophila melanogaster, these authors report that the key feature of these cells is that they have not entered the endocycle, a modified cell cycle through which a cell reproduces its genome several times without dividing.

"The function of endocycle in living organisms is not fully understood," comments Xavier Franch-Marro. "One of the theories is that endoreplication contributes to enlarge the cell and confers the production of high amounts of protein." This is the case of almost all larval cells of Drosophila.

The scientists have observed that the cells that enter the endocycle lose the capacity to reactivate as stem cells. "The endocycle is linked to an irreversible change of gene expression in the cell," explains Jordi Casanova, "We have seen that inhibition of endocycle entry confers the cells the capacity to reactivate as stem cells."

Cell entry into the endocycle is associated with the expression of the Fzr gene. The researchers have found that inhibition of this gene prevents this entry, which in turn leads to the conversion of the cell into an adult progenitor that retains the capacity to reactivate as a stem cell. Therefore, this gene acts as a switch that determines whether a cell will enter mitosis (the normal division of a cell) or the endocycle, the latter triggering a totally different genetic program with a distinct outcome regarding the capacity of a cell to reactivate as a stem cell.

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The above story is based on materials provided by Institute for Research in Biomedicine (IRB Barcelona). Note: Materials may be edited for content and length.

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Mechanism that allows differentiated cell to reactivate as a stem cell revealed

Riordan-McKenna Institute Founders, Neil Riordan, PhD and Orthopedic Surgeon, Dr. Wade McKenna Present at the Mid …

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Chicago, Illinois (PRWEB) October 30, 2014

On October 26th at the Mid American Regenerative and Cellular Medicine Showcase in Chicago, leading applied stem cell research scientist Neil Riordan, PhD and Orthopedic Surgeon, Dr. Wade McKenna presented talks on New Techniques for Enhancing Stem Cell Therapy Effectiveness and Orthopedic Surgical Applications For Stem Cells.

Dr. Riordan focused on historical medical uses of amniotic membrane and the properties of AlphaGEMS that include: wound healing; inflammation and pain reduction; fibrosis risk reduction; growth factor source; adhesion reduction; regeneration support and stem cell enhancement, specifically regarding the mesenchymal stem cells contained within BMAC.

Dr. McKenna discussed the latest applications of BMAC stem cells in orthopedic surgeries like anterior cruciate ligament (ACL) reconstruction and how BMAC injections can virtually eliminate infection risk, reduce complications, increase graft strength, reduce post-surgical inflammation and significantly reduce recovery time. Dr. McKenna also talked about how bone marrow can now be safely and relatively painlessly harvested using his patented BioMAC catheter under local, not general anesthesia.

Dr. Riordan and Dr. McKenna are co-founders of the Riordan-McKenna Institute (RMI), which will be opening soon in Southlake, Texas. RMI will specialize in regenerative orthopedics including non-surgical stem cell therapy and stem cell-enhanced surgery using bone marrow aspirate concentrate (BMAC) and AlphaGEMS amniotic tissue product.

Other noteworthy speakers in attendance included: Paolo Macchiarini, MD-PhD, Arnold Caplan, PhD and Mark Holterman, MD-PhD. Dr. Macchiarini and Dr. Holterman are well known for their work on the first stem cell trachea transplant. Dr. Caplan discovered the mesenchymal stem cell and is commonly referred to as the father of the mesenchymal stem cell.

About Neil Riordan PhD

Dr. Riordan is the co-founder of the Riordan-McKenna Institute (RMI), which will be opening soon in Southlake, Texas. RMI will specialize in regenerative orthopedics including non-surgical stem cell therapy and stem cell-enhanced surgery using bone marrow aspirate concentrate (BMAC) and AlphaGEMS amniotic tissue product.

Dr. Riordan is founder and chief scientific officer of Amniotic Therapies Inc. (ATI). ATI specializes in amniotic tissue research and development. Its current product line includes AlphaGEMS and AlphaPATCH amniotic tissue-based products.

Dr. Riordan is the founder and chairman of Medistem Panama, Inc., (MPI) a leading stem cell laboratory and research facility located in the Technology Park at the prestigious City of Knowledge in Panama City, Panama. Founded in 2007, MPI stands at the forefront of applied research on adult stem cells for several chronic diseases. MPI's stem cell laboratory is ISO 9001 certified and fully licensed by the Panamanian Ministry of Health. Dr. Riordan is the founder of Stem Cell Institute (SCI) in Panama City, Panama (est. 2007).

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Riordan-McKenna Institute Founders, Neil Riordan, PhD and Orthopedic Surgeon, Dr. Wade McKenna Present at the Mid ...

Cellular alchemy turns skin cells into brain cells

By Stem Cell Medicine

Move over stem cells. A different kind of cellular alchemy is allowing cells to be converted directly into other tissues to treat disease or mend injuries.

Stem cells have long been touted as the future of regenerative medicine as they can multiply indefinitely and be turned into many different cell types. Ideally, this would take a personal approach a patient's own cells would be converted into whatever type of cell is required to fix their injury or treat their symptoms. Earlier this year, for instance, people with age-related macular degeneration, the most common cause of blindness in the West, had retinal cells made from their own stem cells injected into their eyes.

Mature cells can be converted into stem cells by exposing them to a cocktail of chemicals that reverts them back to an embryonic-like state. Another set of chemicals is then used to turn the cells into the desired tissue type.

Skipping the stem cell stage would be more efficient, says Andrew Yoo of Washington University in St Louis, Missouri, and would reduce the chance that the new tissue could grow into a tumour a risk with stem cells because of their capacity to regenerate.

Yoo has now managed to do just that, using a process known as "transdifferentiation". His team have turned human skin cells into medium spiny neurons, the cells that go wrong in Huntington's disease.

To the skin cells, the team added two short snippets of genetic material called microRNAs. MicroRNAs are signalling molecules and the two they picked turn on genes in brain cells during embryonic development. They also added four transcription factors another kind of signalling molecule to turn on genes normally active in medium spiny neurons.

Within four weeks the skin cells had changed into MSNs. When put into the brains of mice, the cells survived for at least six months and made connections with the native tissue. "This is a very cool result," says Ronald McKay of the Lieber Institute for Brain Development in Baltimore.

The team's next step is to transplant the cells into mice with a version of Huntington's to see if the new neurons reduce their symptoms.

"Being able to produce cells with medium spiny neuron characteristics directly without first having to generate stem cells is impressive," says Edward Wild of University College London. "Using this offers the tantalising prospect of cell replacement treatments."

Wild points out, however, that before this approach can be used on people with Huntington's, researchers would first have to correct the faulty genetic mutation in their skin cells. And while medium spiny neurons are the first to degenerate in the disease, other brain cells may also be affected. "When it comes to cell replacement we should probably be aiming for a cocktail of cells," says Wild.

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Cellular alchemy turns skin cells into brain cells

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