Umbilical cord blood helps to save lives

SOUTH BEND, Ind.--- In the 1970's, researchers discovered that a newborn's umbilical cord blood contained special stem cells that could help fight certain diseases.

More than 30 years later doctors are still experimenting and learning more about the use of cord blood.

Amanda Canale doesn't take time with her daughter and niece for granted.

She's just happy to feel good.

"I've been in the hospital, and I've been sick my whole life," said Amanda.

Amanda was born with a rare blood disorder that required daily shots.

"Basically, I have no white blood cells. I have no immune system at all," said Amanda

At 23 she developed Leukemia and was given two weeks to live.

She desperately needed a Bone Marrow Transplant, but family members weren't matches.

Her doctor suggested an Umbilical Cord Blood Transplant.

See more here:
Umbilical cord blood helps to save lives

Children's Research Institute Finds Key to Identifying, Enriching Mesenchymal Stem Cells

Contact Information

Available for logged-in reporters only

Newswise DALLAS June 20, 2014 The Childrens Medical Center Research Institute at UTSouthwestern (CRI) has identified a biomarker that enables researchers to accurately characterize the properties and function of mesenchymal stem cells (MSCs) in the body. MSCs are the focus of nearly 200 active clinical trials registered with the National Institutes of Health, targeting conditions such as bone fractures, cartilage injury, degenerative disc disease, and osteoarthritis.

The finding, published in the journal Cell Stem Cell on June 19, significantly advances the field of MSC biology, and if the same biomarker identified in CRIs studies with mice works in humans, the outlook for clinical trials that use MSCs will be improved by the ability to better identify and characterize the relevant cells.

There has been an increasing amount of clinical interest in MSCs, but advances have been slow because researchers to date have been unable to identify MSCs and study their normal physiological function in the body, said Dr. Sean Morrison, Director of the Childrens Research Institute, Professor of Pediatrics at UTSouthwestern Medical Center, and a Howard Hughes Medical Institute Investigator. We found that a protein known as leptin receptor can serve as a biomarker to accurately identify MSCs in adult bone marrow in vivo, and that those MSCs are the primary source of new bone formation and bone repair after injury.

In the course of their investigation, the CRI researchers found that leptin receptor-positive MSCs are also the main source of factors that promote the maintenance of blood-forming stem cells in the bone marrow.

Unfortunately, many clinical trials that are testing potential therapies using MSCs have been hampered by the use of poorly characterized and impure collections of cultured cells, said Dr. Morrison, senior author of the study and holder of the Mary McDermott Cook Chair in Pediatric Genetics at UTSouthwestern. If this finding is duplicated in our studies with human MSCs, then it will improve the characterization of MSCs that are used clinically and could increase the probability of success for well-designed clinical trials using MSCs.

Dr. Bo Zhou, a postdoctoral research fellow in Dr. Morrisons laboratory, was first author of the paper. Other CRI researchers involved in the study were Drs. Rui Yue and Malea Murphy, both postdoctoral research fellows. The research was supported by the National Heart, Lung, and Blood Institute, the Cancer Prevention and Research Institute of Texas, and donors to the Childrens Medical Center Foundation.

About CRI

Childrens Medical Center Research Institute at UTSouthwestern (CRI) is a joint venture established in2011 to build upon the comprehensive clinical expertise of Childrens Medical Center of Dallas and the internationally recognized scientific excellence of UTSouthwestern Medical Center. CRIs mission is to perform transformative biomedical research to better understand the biological basis of disease, seeking breakthroughs that can change scientific fields and yield new strategies for treating disease. Located in Dallas, Texas, CRI is creating interdisciplinary groups of exceptional scientists and physicians to pursue research at the interface of regenerative medicine, cancer biology and metabolism, fields that hold uncommon potential for advancing science and medicine. More information about CRI is available on its website: cri.utsw.edu

View post:
Children's Research Institute Finds Key to Identifying, Enriching Mesenchymal Stem Cells

Cedars-Sinai Medical Tipsheet for June

Contact Information

Available for logged-in reporters only

Newswise Following is the June tipsheet of story ideas from Cedars-Sinai Medical Center. To arrange interviews, please contact the individual listed.

Enzyme Used in Antidepressants Could Help Researchers Develop Prostate Cancer Treatments An international team of scientists including researchers at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute and the University of Southern California found that an enzyme commonly used as a target for antidepressants may also promote prostate cancer growth. The study, published in the Journal of Clinical Investigation, found that suppressing the enzyme monoamine oxidase A, or MAOA, may reduce or even eliminate prostate tumor growth and metastasis in laboratory mice. The finding could open the door for physicians to use antidepressants to fight prostate cancer. Currently, drugs that inhibit MAOA enzymes are used to treat patients with mental illnesses like depression. CONTACT: Cara Martinez, 310-423-7798; Email cara.martinez@cshs.org

Cedars-Sinai Science and Medicine Graduate Program Awards PhDs to Second Graduating Class Cedars-Sinais Graduate Program in Biomedical Science and Translational Medicine will confer doctoral degrees on six students during a commencement ceremony June 12. The students -- whose research focused on heart disease, cancer, inflammatory bowel disease, neurodegenerative disease and protective immunities against bacterial infections comprise the medical centers second graduating class. Seven doctoral students were the first to graduate from the program in 2013. CONTACT: Duke Helfand, 310-248-6608; Email duke.helfand@cshs.org

Cedars-Sinai Physician Groups Receive Highest Rating for Fifth Consecutive Year For the fifth year in a row, Cedars-Sinai Medical Group and Cedars-Sinai Health Associates have been awarded the highest possible designation for quality care by a leading national organization representing managed care physician groups. CAPG, formerly known as the California Association of Physician Groups, rated both Cedars-Sinai groups as excelling in all six of the criteria used in the 2014 Standards of Excellence survey. Both CSMG and CSHA groups voluntarily participated in the annual survey that rated 86 medical groups, representing 11.1 million patients nationwide. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Stem Cell Expert Explains How Experimental Regenerative Medicine Therapies Can Regrow Damaged Heart Muscle Stem cell therapy for cardiovascular disease isnt a medical pipe dream its a reality today, although patients need to better understand the complex science behind these experimental treatments, according to the chief of Cardiology for the Cedars-Sinai Heart Institute. In a 17-minute TEDxGrandForks talk now available on YouTube.com, Timothy D. Henry, MD, known for his innovative work in developing stem cell treatments for advanced heart disease patients, said he understands why so many are confused about the latest scientific findings. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Arthur J. Ochoa Receives Mexican American Bar Foundation Professional Achievement Award The Mexican American Bar Foundation named Arthur J. Ochoa, Cedars-Sinais senior vice president of Community Relations and Development, the 2014 recipient of the legal organizations Professional Achievement Award. The award was presented at the Mexican American Bar Foundations Annual Scholarship and Awards Gala June 14 at the Millennium Biltmore Hotel in downtown Los Angeles. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

For Patients With Sickle Cell Disease, Blood Donors Are a Matter of Life and Death Every six weeks for the past nine years, Mawasi Belle has been donating blood at Cedars-Sinais Blood Donor Services, totaling nearly 80 trips to the medical institution and thousands of pints of blood collected. But for Belle, this selfless act is merely a part of her lifestyle. My decision to give is easy. If I do not donate, patients with serious blood diseases, like sickle cell anemia, will die. And Belle is right: Patients with sickle cell disease and other serious blood conditions rely on donors to keep their blood flowing and hearts beating. CONTACT: Cara Martinez, 310-423-7798; Email cara.martinez@cshs.org

Hypertension Expert Awarded $8.5 Million to Enlist African-American Barbers in Fight Against Hypertension A Cedars-Sinai Heart Institute physician has been awarded an $8.5 million grant aimed at enlisting African-American barbers in the fight against hypertension, a deadly condition that can cause strokes, heart attacks and organ failure, and which is particularly devastating to African-American men. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Link:
Cedars-Sinai Medical Tipsheet for June

Endonovo Therapeutics to Develop Next Generation, Off-The-Shelf, Cell Free Regenerative Products

SOURCE: Endonovo Therapeutics, Inc.

Dr. Leonard Makowka, a Leading Authority in Hepatic Science, Joins Endonovo Therapeutics as Its Chief Medical Officer

LOS ANGELES, CA--(Marketwired - Jun 11, 2014) - Endonovo Therapeutics, Inc. (OTCQB: ENDV) ("Endonovo" or the "Company"), a biotechnology company developing innovative regenerative therapies, announced today that it has created technologies to pursue the development and manufacturing of next generation regenerative products that no longer require the administration of stem cells. Endonovo's "Cell Free" products will harness the biological molecules secreted by cells to create truly "off-the-shelf" therapeutics that can be delivered to patients in a much timelier manner than is possible with autologous and allogeneic stem cell therapies.

There are currently more than 300 mesenchymal stem cell clinical trials underway to treat a wide range of pathological conditions listed on the ClinicalTrials.gov database. These clinical trials are still based on the transplantation of mesenchymal stem cells. Endonovo is developing therapies that may mitigate many of the current drawbacks of cell-based therapies, such as the low survival and engraftment rate of transplanted stem cells, the risk of occlusion in microvasculature, and unregulated growth, such as hyper-innervation or ossification and/or calcification in the body.

"Cell Free" regenerative products may also mitigate many of the limitations to the commercialization of stem cell therapies, such as the manufacturing, storage and delivery of viable cells. "Cell Free" regenerative products are commercially more attractive because they are simpler to manufacture, easier to store and maintain their therapeutic potency for longer periods of time when compared to stem cells.

Additionally, Endonovo Therapeutics announced that it has appointed Dr. Leonard Makowka, M.D., Ph.D., to serve as the Company's Chief Medical Officer. Dr. Makowka was formerly the Chairman of the Department of Surgery and Director of Transplantation Services at Cedars Sinai Medical Center in Los Angeles, CA, and served as Professor of Surgery at the UCLA School of Medicine. He was also Executive Director of the Comprehensive Liver Disease Center, which used a multiple disciplinary approach to the treatment of liver disease, at St. Vincent's Medical Center in Los Angeles, CA. He has published over 400 articles and chapters in both clinical and basic scientific research and has been regarded as a leading authority in hepatic science. Dr. Makowka has also served as a board member of various public and private healthcare and life science companies.

"We are very pleased to welcome Dr. Makowka to the Endonovo team," said Endonovo Therapeutics CEO, Alan Collier. "His experience and expertise will be a tremendous asset in the development of 'cell-free' therapeutics that can promote the regeneration of tissues without the need to inject stem cells into the body, which would result in safer, more effective therapies, lower costs and the saving of lives."

"I am excited to join Endonovo Therapeutics and help the company develop its 'cell-free' therapeutic platform," stated Dr. Leonard Makowka, Chief Medical Officer at Endonovo Therapeutics. "Although it is early in the developmental lifecycle, we are excited about the development of first-in-class, 'cell free' regenerative products that can protect and stimulate the regeneration of tissues. These products would be truly 'off-the-shelf' therapies that could be quickly administered following organ injuries, such as a heart attack, a stroke, acute and/or chronic liver disease and the 'aging' of organs, in order to protect the organ and begin healing it."

About Endonovo Therapeutics

Endonovo Therapeutics, Inc. is a publicly traded biotechnology company developing off-the-shelf, cell free regenerative products and non-invasive, bioelectronic therapies designed to extend and enhance the human life by regenerating tissues and organs that have become injured or damaged due to disease and age. The Company is developing therapies for various inflammatory, autoimmune and degenerative diseases using biomolecules secreted from cells and Time-Varying Electromagnetic Fields (TVEMF).

More:
Endonovo Therapeutics to Develop Next Generation, Off-The-Shelf, Cell Free Regenerative Products

Umbilical cord transplants saving lives

LOS ANGELES (KABC) --

Amanda Canale doesn't take time with her daughter and niece for granted. She's just happy to feel good.

"I've been in the hospital, and I've been sick my whole life," Amanda said.

Amanda was born with a rare blood disorder that required daily shots.

"Basically, I have no white blood cells," Amanda said. "I have no immune system at all."

At 23, she developed leukemia and was given two weeks to live. She desperately needed a bone marrow transplant, but family members weren't matches. Her doctor suggested an umbilical cord blood transplant.

"The cord was a perfect match and it was available, so it was the right solution for her," Edward Agura, MD, Medical Director of Bone Marrow Transplantation, Baylor University Medical Center, Dallas, said.

Cord blood contains stem cells that regenerate. Mothers of newborns can save their child's own blood or donate it. More than 30,000 transplants have been performed worldwide. However, because the blood comes from a tiny newborn, there's not much of it.

"The cord blood is rare, precious and few, and yet is more potent in its ability to grow," Dr. Agura said.

Now, doctors at Baylor are treating patients by combining cord blood from multiple donors. They've found this increases the number of stem cells and provides faster recovery. Amanda's transfusion was from a baby whose mother donated six years earlier. The procedure completely cured her cancer and blood disorder.

See the rest here:
Umbilical cord transplants saving lives

Stem Cells Successfully Transplanted And Grown In Pigs

June 5, 2014

Nathan Hurst, University of Missouri

One of the biggest challenges for medical researchers studying the effectiveness of stem cell therapies is that transplants or grafts of cells are often rejected by the hosts. This rejection can render experiments useless, making research into potentially life-saving treatments a long and difficult process. Now, researchers at the University of Missouri have shown that a new line of genetically modified pigs will host transplanted cells without the risk of rejection.

The rejection of transplants and grafts by host bodies is a huge hurdle for medical researchers, said R. Michael Roberts, Curators Professor of Animal Science and Biochemistry and a researcher in the Bond Life Sciences Center. By establishing that these pigs will support transplants without the fear of rejection, we can move stem cell therapy research forward at a quicker pace.

In a published study, the team of researchers implanted human pluripotent stem cells in a special line of pigs developed by Randall Prather, an MU Curators Professor of reproductive physiology. Prather specifically created the pigs with immune systems that allow the pigs to accept all transplants or grafts without rejection. Once the scientists implanted the cells, the pigs did not reject the stem cells and the cells thrived. Prather says achieving this success with pigs is notable because pigs are much closer to humans than many other test animals.

Many medical researchers prefer conducting studies with pigs because they are more anatomically similar to humans than other animals, such as mice and rats, Prather said. Physically, pigs are much closer to the size and scale of humans than other animals, and they respond to health threats similarly. This means that research in pigs is more likely to have results similar to those in humans for many different tests and treatments.

Now that we know that human stem cells can thrive in these pigs, a door has been opened for new and exciting research by scientists around the world, Roberts said. Hopefully this means that we are one step closer to therapies and treatments for a number of debilitating human diseases.

Roberts and Prather published their study, Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency in the Proceedings of the National Academy of Sciences.

Source: Nathan Hurst, University of Missouri

Link:
Stem Cells Successfully Transplanted And Grown In Pigs

University of Michigan Stem Cell Research | Overview

The University of Michigan has recently emerged as a national leader in the three main types of stem cell research: embryonic, adult, and reprogrammed cells known as iPS cells.

A long-time leader in the study of adult stem cells, U-M has bolstered its human embryonic stem cell program, and added a complementary iPS cell research effort, since the passage of Proposal 2 in November 2008. The state constitutional amendment eased onerous restrictions on the types of embryonic stem cell research allowed in Michigan.

Recent milestones include:

In addition to the work underway by the Consortium for Stem Cell Therapies, hubs for U-M stem cell research also exist at the Life Science Institutes Center for Stem Cell Biology and at the U-M Health Systems Comprehensive Cancer Center. Other groundbreaking stem cell work is being pursued at other units across campus.

The Center for Stem Cell Biology was established in 2005 with $10.5 million provided by the U-M Medical School, the Life Sciences Institute, and the Molecular and Behavioral Neurosciences Institute.

The centers main goal is to determine the fundamental mechanisms that regulate stem cell function. That knowledge, in turn, provides new insights into the origins of disease and suggests new approaches to disease treatment. Most of the work involves adult stem cells including blood-forming and nervous system stem cells but human embryonic stem cells also are studied.

The U-M Comprehensive Cancer Center is one of the few places in North America that has made an institutional commitment to cancer stem cell research. Cancer stem cells are responsible for triggering the uncontrolled cell growth that leads to malignant tumors.

U-M researchers were the first to identify stem cells in solid tumors, finding them in breast cancer in 2003. They were also the first to find pancreatic and head-and-neck stem cells. At the U-M cancer center, scientists are investigating how these cells mutate, causing unregulated growth that ultimately leads to cancer.

Read more here:
University of Michigan Stem Cell Research | Overview

Cancer Centers Combine Expertise To Optimize Advanced Immunotherapy Strategies

Washington /PRNewswire/ - Physician researchers from Georgetown Lombardi Comprehensive Cancer Center, in Washington, D.C., and John Theurer Cancer Center (JTCC) in Hackensack, New Jersey, announce today the formation of the Regional Immunotherapy Discovery Program.

The Regional Immunotherapy Discovery Program will accelerate discovery and implementation of a new immunotherapy approach, which combines the full potential of two potent strategies currently used in treating cancer: cancer immunotherapy and bone marrow stem cell transplantation.

"We are at the dawn of an exciting new era," explains Louis M. Weiner, MD, director of Georgetown Lombardi. "The future of successful cancer therapy will rely heavily upon immunotherapythe power of the immune system to recognize and destroy malignant cells, and then to remember and eliminate cancers that try to recur."

Georgetown Lombardi, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, and JTCC, part of Hackensack University Medical Center, already offer the most advanced clinical trials available using investigational immunotherapy drugs. And both offer transplant programs that manipulate the immune cells via both allogeneic (donor) and autologous (patient) transplants to treat patients with blood cancers.

"By combining these two strategies in attacking cancer, we believe it's possible to optimize the true promise of immunotherapy and extend treatment options to specific patient populations," says Andr Goy, MD, MS, chairman of JTCC. "This approach is only now emerging at a very limited number of cancer centers in the U.S."

One example of the new strategy would be to combine an immunotherapy drug such as a PD-1 inhibitor, which selectively unleashes immune cells, with an adoptive cellular therapy to assist reconstitution of the immune system following immune cell-depleting chemotherapy. This strategy is designed to deliver an overwhelming blow against a blood cancer.

In addition to the therapeutic impact, the Regional Immunotherapy Discovery Program has broad regional accessibility via physician researchers from Georgetown Lombardi in Washington, the MedStar Georgetown Cancer Network in Maryland and Washington, Regional Cancer Care Associates (RCCA) with offices throughout New Jersey, and JTTC in Hackensack. This means cancer patients living in the northeast corridor between Washington and the New York metropolitan area will have easy access to state-of-the-art immunotherapy clinical trials and care.

Michael B. Atkins, MD, an internationally recognized expert in immunotherapy and deputy director of Georgetown Lombardi, and Andrew L. Pecora, MD, president of RCCA, will lead the program, which builds on an oncology affiliation that Georgetown Lombardi, a National Cancer Institute (NCI) designated-comprehensive cancer center, and JTCC established in 2013. As part of the affiliation, the two institutions are working toward becoming an NCI-recognized consortium center, in which investigators from separate but collaborating scientific institutions contribute actively to the development and actualization of a specific cancer research agenda.

About John Theurer Cancer Center at Hackensack University Medical Center John Theurer Cancer Center at Hackensack UMC is among the nation's top 50 U.S. News & World Report Best Hospitals for cancer the highest-ranked inNew Jersey with this designation. It is ;New Jersey's largest and most comprehensive cancer center dedicated to the diagnosis, treatment, management, research, screenings, preventive care, as well as survivorship of patients with all types of cancer.

Each year, more people in the New Jersey/New York metropolitan area turn to the John Theurer Cancer Center for cancer care than to any other facility in New Jersey. The 14 specialized divisions feature a team of medical, research, nursing, and support staff with specialized expertise that translates into more advanced, focused care for all patients. The John Theurer Cancer Center provides comprehensive multidisciplinary care, state of the art technology, access to clinical trials, compassionate care and medical expertiseall under one roof. Physicians at the John Theurer Cancer Center are members of Regional Cancer Care Associates one of the nation's largest professional hematology/oncology groups. For more information please visit jtcancercenter.org.

Here is the original post:
Cancer Centers Combine Expertise To Optimize Advanced Immunotherapy Strategies

Future heat stroke treatment found in dental pulp stem cells

PUBLIC RELEASE DATE:

5-Jun-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (June 5, 2014) Scientists in Taiwan have found that intravenous injections of stem cells derived from human exfoliated deciduous tooth pulp (SHED) have a protective effect against brain damage from heat stroke in mice. Their finding was safe and effective and so may be a candidate for successfully treating human patients by preventing the neurological damage caused by heat stroke.

The study is published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT1100Tseng.

"Heat stroke deaths are increasing worldwide and heat stroke-induced brain injury is the third largest cause of mortality after cardiovascular disease and traumatic brain injury," said study lead author Dr. Ying-Chu Lin of the Kaohsiung Medical University School of Dentistry, Kaohsiung City, Taiwan. "Heat stroke is characterized by hyperthermia, systemic inflammatory response, multiple organ failure and brain dysfunction."

To investigate the beneficial and potentially therapeutic effects afforded by the protective activities of self-renewing stem cells derived from human exfoliated deciduous teeth, the scientists transplanted SHED into mice that had suffered experimental heat stroke.

According to the research team, these cells have "significantly higher proliferation rates" than stem cells from bone marrow and have the added advantages of being easy to harvest and express several growth factors, including vascular endothelial growth factor (VEGF), and they can promote the migration and differentiation of neuronal progenitor cells (NPCs).

"We observed that the intravenous administration of SHED immediately post-heat stroke exhibited several therapeutic benefits," said Dr. Lin. "These included the inhibition of neurological deficits and a reduction in oxidative damage to the brain. We suspect that the protective effect of SHED may be related to a decreased inflammatory response, decreased oxidative stress and an increase in hypothalamo-pituitary-adrenocortical axis activity following the heat stroke injury."

There are currently some drawbacks to the experimental therapy, said the researchers. First, there is a limited supply of SHED. Also, SHED transplantation has been associated with cancer and immune rejection.

Go here to see the original:
Future heat stroke treatment found in dental pulp stem cells

How planarians maintain their stem cell pools over generations

6 hours ago Fig. 1: Pluripotent stem cells enable planarians to achieve extraordinary feats of regeneration. (A) Planarians are able to re-grow an entire head in a matter of a few days. (B) The stem cells and their early offspring can be found almost all over the worms body. During regeneration, when a lot of new tissue has to be produced, they are able to generate a wide variety of cell types. The cell nuclei are marked in blue. Tissue-specific markers are marked in red, green and white. Credit: Max Planck Institute for Molecular Biomedicine /Bartscherer

Planarians are known as masters of regeneration: they can re-build any part of their bodies after amputation. This ability relies on a large number of pluripotent stem cells. To further investigate the mechanisms that enable planarians to maintain their stem cell pool over generations, scientists have now established a method for analysing the composition of planarian stem cells and the turnover of their proteins. They discovered a protein that is not only required for the maintenance of the stem cell pool in planarians, but might also be active in the pluripotent stem cells of mammals.

Of earthworms and flatworms

Everyone knows the myth about earthworms: if you cut them in half, you get two worms. Nothing could be further from the truth, alas. However, if the earthworm is replaced by a flatworm, the two parts can survive these childish experiments. What's more, be it skin, intestine or brain, the body part lost through cutting will simply grow again in a matter of days. The creatures involved here are planarians[1], a class of flatworms that are so flat that they need neither lungs nor a heart to take in and distribute oxygen in their bodies. So simple and yet so ingenious? It would appear so. Regeneration studies involving these animals have shown that a dismembered planarian can generate several hundred tiny animals, hence they could "almost be called immortal under the edge of a knife" (Dalyell, 1814). The astonishing aspect here is that both the blueprint and construction material for the regeneration process must be contained in each of the fragments: a small piece of tail, for example, becomes a complete worm under the animal's own strength and using existing resources.

Not the preserve of youth: pluripotency also available in adults

So where do the components needed to rebuild the cellular structures come from? In their search for the answer to this question, scientists have a population of small cells in their sights, namely the approximately five-micrometre-long neoblasts. These cells are found almost everywhere in the planarian body and behave like stem cells: they divide, renew and can form the different cell types that have been lost as a result of amputation (Fig. 1). When the planarian loses a body part or discards its tail for reproduction, the neoblasts are reactivated and migrate to the wound. They divide there and their offspring form a blastema, in which as a result of interplay between various extra- and intra-cellular factors important differentiation and patterning processes take place. Thanks to these processes, in turn, complex structures like the brain are formed. If the neoblasts are eliminated through radiation, for example, the planarian loses its ability to regenerate and dies within a few weeks. The fact that, following transplantation into an irradiated, neoblast-free worm, a single neoblast can produce all cell types and enable the host worm to regain its ability to regenerate shows that at least some neoblasts are pluripotent [2]. In healthy mammals, pluripotency, that is the ability of one cell to produce any given cell type found in an organism, e.g. muscle, nerve or pancreas cells, only arises in the early embryonic stage. Therefore, stable pluripotency in the adult organism is something special but not impossible as long as mechanisms exist for conserving this characteristic as is clearly the case with the planarians.

An in-vivo Petri dish for pluripotent stem cells

The preservation of pluripotency has been an important topic in stem cell research for years, and has mostly been examined up to now using isolated embryonic stem cells. Important transcription factors that can induce and preserve pluripotency were discovered in the course of this research. So what can planarians contribute to the current research if their stem cells cannot be cultivated and reproduced outside of the body? This is precisely where the strength of the planarians as a model system in stem cell research lies: the combination they can offer of a natural extracellular environment and pluripotent stem cells. Whereas cultivated stem cells are normally taken out of their natural environment and all important interactions with neighbouring cells and freely moving molecules are interrupted as a result, the stem cells in planarians can be observed and manipulated under normal conditions in vivo. Therefore, planarians are of interest as "in-vivo Petri dishes" for stem cells, in which not only their mechanisms for preserving pluripotency can be studied, but also their regulation and contribution to regeneration.

A venerable old worm meets ultra-modern next-generation technologies

Although planarians have been renowned as masters of regeneration and research objects for generations, they have undergone a genuine explosion in research interest in recent years. In particular, the possibility of switching off specific genes through RNA interference (RNAi) and the availability of the genome sequence of Schmidtea mediterranea, a planarian species which is especially good at regenerating itself, have contributed to this surge in interest. With the development of modern sequencing procedures, that is 'next generation sequencing', gene expression profiles that provide information about the specific genes activated in particular cells or tissues at particular points in time can now be produced on a large scale. Hence, it is possible to examine which messenger RNAs (mRNAs) are produced that act as molecular templates for the production of proteins. For example, hundreds of these mRNAs are produced after the amputation of a worm's head and their proteins provide potential regulators of the regeneration process [3; 4]. However, the real work only starts here: the extent to which the presence of a particular mRNA also reflects the volume of protein that is active in the cell remains to be determined. It is mainly the proteins in the form of enzymes, signalling molecules and structural elements, and not their mRNAs, that ultimately control the majority of cellular processes. In addition, their production using mRNA templates and their lifetime are precisely regulated processes and the frequency with which an mRNA arises cannot provide any information about these processes. The time has come, therefore, to develop experimental approaches for planarians that extend beyond gene expression analysis and lend greater significance to the subsequent regulatory processes.

Read more here:
How planarians maintain their stem cell pools over generations