Durham, NC (PRWEB) December 18, 2013

A new study released today in STEM CELLS Translational Medicine demonstrates that the therapeutic value of stem cells collected from fat declines when the cells come from older patients.

This could restrict the effectiveness of autologous cell therapy using fat, or adipose-derived mesenchymal stromal cells (ADSCs), and require that we test cell material before use and develop ways to pretreat ADSCs from aged patients to enhance their therapeutic potential, said Anastasia Efimenko, M.D., Ph.D. She and Nina Dzhoyashvili, M.D., were first authors of the study led by Yelena Parfyonova, M.D., D.Sc., at Lomonosov Moscow State University, Moscow.

Cardiovascular disease remains the most common cause of death in most countries. Mesenchymal stromal cells (MSCs), stem cells collected from either bone marrow or adipose tissue, are considered one of the most promising therapeutic agents for regenerating damaged tissue because of their proliferation potential and ability to be coaxed into different cell types. Importantly, they also have the ability to stimulate the growth of new blood vessels, a process known as angiogenesis.

Adipose tissue in particular is considered an ideal source for MSCs because it is largely dispensable and the stem cells are easily accessible in large amounts using a minimally invasive procedure. ADSCs have been used in several clinical trials looking at cell therapy for heart conditions, but most of the studies employed cells taken from relatively healthy young donors rather than sick, older ones the typical patient when it comes to heart disease.

We knew that aging and disease itself may negatively affect MSC activities, Dr. Dzhoyashvili said. So the aim of our study was to investigate how patient age affects the properties of ADSCs, with special emphasis on their ability to stimulate angiogenesis.

The team analyzed age-associated changes in ADSCs collected from patients of different age groups, including some with coronary artery disease and some without. The results showed that ADSCs from the older patients in both groups expressed various age markers, including shorter telomeres, and, thus, confirmed that ADSCs did age. Telomeres, the regions of repetitive DNA at the end of a chromosome, protect it from deterioration.

We showed that ADSCs from older patients both with and without coronary artery disease produced significantly less amounts of angiogenesis-stimulating factors compared with the younger patients in the study and their angiogenic capabilities lessened, Dr. Efimenko concluded. The results provide new insight into molecular mechanisms underlying the age-related decline of stem cells therapeutic potential.

These findings are significant because the successful development of cell therapies depends on a thorough understanding of how age may affect the regenerative potential of autologous cells, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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Study Shows Therapeutic Potential of Fat-derived Stem Cells Declines As Donor’s Age Rises

In a typical stem cell transplant for cancer very high doses of chemo are used, often along with radiation therapy, to try to destroy all the cancer cells. This treatment also kills the stem cells in the bone marrow. Soon after treatment, stem cells are given to replace those that were destroyed. These stem cells are given into a vein, much like a blood transfusion. Over time they settle in the bone marrow and begin to grow and make healthy blood cells. This process is called engraftment.

There are 3 basic types of transplants. They are named based on who gives the stem cells.

These stem cells come from you alone. In this type of transplant, your stem cells are taken before you get cancer treatment that destroys them. Your stem cells are removed, or harvested, from either your bone marrow or your blood and then frozen. To find out more about that process, please see the section Whats it like to donate stem cells? After you get high doses of chemo and/or radiation the stem cells are thawed and given back to you.

One advantage of autologous stem cell transplant is that you are getting your own cells back. When you donate your own stem cells you dont have to worry about the graft attacking your body (graft-versus-host disease) or about getting a new infection from another person. But there can still be graft failure, and autologous transplants cant produce the graft-versus-cancer" effect.

This kind of transplant is mainly used to treat certain leukemias, lymphomas, and multiple myeloma. Its sometimes used for other cancers, like testicular cancer and neuroblastoma, and certain cancers in children. Doctors are looking at how autologous transplants might be used to treat other diseases, too, like systemic sclerosis, multiple sclerosis, Crohn disease, and systemic lupus erythematosis.

A possible disadvantage of an autologous transplant is that cancer cells may be picked up along with the stem cells and then put back into your body later. Another disadvantage is that your immune system is still the same as before when your stem cells engraft. The cancer cells were able to grow despite your immune cells before, and may be able to do so again.

To prevent this, doctors may give you anti-cancer drugs or treat your stem cells in other ways to reduce the number of cancer cells that may be present. Some centers treat the stem cells to try to remove any cancer cells before they are given back to the patient. This is sometimes called purging. It isnt clear that this really helps, as it has not yet been proven to reduce the risk of cancer coming back (recurrence).

A possible downside of purging is that some normal stem cells can be lost during this process, causing the patient to take longer to begin making normal blood cells, and have unsafe levels of white blood cells or platelets for a longer time. This could increase the risk of infections or bleeding problems.

One popular method now is to give the stem cells without treating them. Then, after transplant, the patient gets a medicine to get rid of cancer cells that may be in the body. This is called in vivo purging. Rituximab (Rituxan), a monoclonal antibody drug, may be used for this in certain lymphomas and leukemias, and other drugs are being tested. The need to remove cancer cells from transplants or transplant patients and the best way to do it is being researched.

Doing 2 autologous transplants in a row is known as a tandem transplant or a double autologous transplant. In this type of transplant, the patient gets 2 courses of high-dose chemo, each followed by a transplant of their own stem cells. All of the stem cells needed are collected before the first high-dose chemo treatment, and half of them are used for each transplant. Most often both courses of chemo are given within 6 months, with the second one given after the patient recovers from the first one.

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Types of stem cell transplants for treating cancer

PUBLIC RELEASE DATE:

18-Dec-2013

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

Putnam Valley, NY. (Dec. 18, 2013) Multiple sclerosis (MS), an inflammatory autoimmune disease affecting more than one million people worldwide, is caused by an immune reaction to myelin proteins, the proteins that help form the myelin insulating substance around nerves. Demyelination and MS are a consequence of this immune reaction. Bone marrow mesenchymal stem cells (MSCs) have been considered as an important source for cell therapy for autoimmune diseases such as MS because of their immunosuppressive properties.

Now, a research team in Brazil has compared MSCs isolated from MS patients and from healthy donors to determine if the MSCs from MS patients are normal or defective. The study will be published in a future issue of Cell Transplantation but is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct1131.

"The ability of MSCs to modulate the immune response suggests a possible role of these cells in tolerance induction in patients with autoimmune diseases, and also supports the rationale for MSC application in the treatment of MS," said study corresponding author Dr. Gislane Lelis Vilela de Oliveira of the Center for Cell-Based Research at the University of Sao Paulo. "We found that MS patient-derived MSCs present higher senescence, or biological aging, and decreased expression of important immune system markers as well as a different transcriptional profile when compared to their healthy counterparts."

The researchers suggested that further clinical studies should be conducted using transplanted allogenic (other-donated) MSCs derived from healthy donors to determine if the MSCs have a therapeutic effect over transplanted autologous (self-donated) MSCs from patients.

"Several reports have shown that bone marrow-derived MSCs are able to modulate innate and adaptive immunity cell responses and induce tolerance, thus supporting the rationale for their application in treating autoimmune diseases, " said the researchers.

They also noted that studies have shown that transplanted MSCs migrate to demyelinated areas as well as induce generation and expansion of regulatory T cells, important in immunity.

"We found that the transcriptional profile of patient MSCs after transplantation was closer to that of their pre-transplant MSC samples than those from their healthy counterparts, suggesting that treatment with patient self-donated MSCs does not reverse the alterations we observed in MSCs from MS patients," they concluded.

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Preferable treatment for MS found in allogenic bone marrow stem cells

PUBLIC RELEASE DATE:

18-Dec-2013

Contact: Kevin Punsky punsky.kevin@mayo.edu 904-953-2299 Mayo Clinic

JACKSONVILLE, Fla. -- Abba Zubair, M.D., Ph.D, believes that cells grown in the International Space Station (ISS) could help patients recover from a stroke, and that it may even be possible to generate human tissues and organs in space. He just needs a chance to demonstrate the possibility.

He now has it. The Center for the Advancement of Science in Space (CASIS), a nonprofit organization that promotes research aboard the ISS, has awarded Dr. Zubair a $300,000 grant to send human stem cells into space to see if they grow more rapidly than stem cells grown on Earth.

Dr. Zubair, medical and scientific director of the Cell Therapy Laboratory at Mayo Clinic in Florida, says the experiment will be the first one Mayo Clinic has conducted in space and the first to use these human stem cells, which are found in bone marrow.

"On Earth, we face many challenges in trying to grow enough stem cells to treat patients," he says. "It now takes a month to generate enough cells for a few patients. A clinical-grade laboratory in space could provide the answer we all have been seeking for regenerative medicine."

He specifically wants to expand the population of stem cells that will induce regeneration of neurons and blood vessels in patients who have suffered a hemorrhagic stroke, the kind of stroke which is caused by blood clot. Dr. Zubair already grows such cells in his Mayo Clinic laboratory using a large tissue culture and several incubators -- but only at a snail's pace.

Experiments on Earth using microgravity have shown that stem cells -- the master cells that produce all organ and tissue cell types -- will grow faster, compared to conventionally grown cells.

"If you have a ready supply of these cells, you can treat almost any condition, and can theoretically regenerate entire organs using a scaffold," Dr. Zubair says. "Additionally, they don't need to come from individual patients -- anyone can use them without rejection."

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Mayo Clinic researcher to grow human cells in space to test treatment for stroke

by Jos Domen*, Amy Wagers** and Irving L. Weissman***

Blood and the system that forms it, known as the hematopoietic system, consist of many cell types with specialized functions (see Figure 2.1). Red blood cells (erythrocytes) carry oxygen to the tissues. Platelets (derived from megakaryocytes) help prevent bleeding. Granulocytes (neutrophils, basophils and eosinophils) and macrophages (collectively known as myeloid cells) fight infections from bacteria, fungi, and other parasites such as nematodes (ubiquitous small worms). Some of these cells are also involved in tissue and bone remodeling and removal of dead cells. B-lymphocytes produce antibodies, while T-lymphocytes can directly kill or isolate by inflammation cells recognized as foreign to the body, including many virus-infected cells and cancer cells. Many blood cells are short-lived and need to be replenished continuously; the average human requires approximately one hundred billion new hematopoietic cells each day. The continued production of these cells depends directly on the presence of Hematopoietic Stem Cells (HSCs), the ultimate, and only, source of all these cells.

Figure 2.1. Hematopoietic and stromal cell differentiation.

2001 Terese Winslow (assisted by Lydia Kibiuk)

The search for stem cells began in the aftermath of the bombings in Hiroshima and Nagasaki in 1945. Those who died over a prolonged period from lower doses of radiation had compromised hematopoietic systems that could not regenerate either sufficient white blood cells to protect against otherwise nonpathogenic infections or enough platelets to clot their blood. Higher doses of radiation also killed the stem cells of the intestinal tract, resulting in more rapid death. Later, it was demonstrated that mice that were given doses of whole body X-irradiation developed the same radiation syndromes; at the minimal lethal dose, the mice died from hematopoietic failure approximately two weeks after radiation exposure.1 Significantly, however, shielding a single bone or the spleen from radiation prevented this irradiation syndrome. Soon thereafter, using inbred strains of mice, scientists showed that whole-body-irradiated mice could be rescued from otherwise fatal hematopoietic failure by injection of suspensions of cells from blood-forming organs such as the bone marrow.2 In 1956, three laboratories demonstrated that the injected bone marrow cells directly regenerated the blood-forming system, rather than releasing factors that caused the recipients' cells to repair irradiation damage.35 To date, the only known treatment for hematopoietic failure following whole body irradiation is transplantation of bone marrow cells or HSCs to regenerate the blood-forming system in the host organisms.6,7

The hematopoietic system is not only destroyed by the lowest doses of lethal X-irradiation (it is the most sensitive of the affected vital organs), but also by chemotherapeutic agents that kill dividing cells. By the 1960s, physicians who sought to treat cancer that had spread (metastasized) beyond the primary cancer site attempted to take advantage of the fact that a large fraction of cancer cells are undergoing cell division at any given point in time. They began using agents (e.g., chemical and X-irradiation) that kill dividing cells to attempt to kill the cancer cells. This required the development of a quantitative assessment of damage to the cancer cells compared that inflicted on normal cells. Till and McCulloch began to assess quantitatively the radiation sensitivity of one normal cell type, the bone marrow cells used in transplantation, as it exists in the body. They found that, at sub-radioprotective doses of bone marrow cells, mice that died 1015 days after irradiation developed colonies of myeloid and erythroid cells (see Figure 2.1 for an example) in their spleens. These colonies correlated directly in number with the number of bone marrow cells originally injected (approximately 1 colony per 7,000 bone marrow cells injected).8 To test whether these colonies of blood cells derived from single precursor cells, they pre-irradiated the bone marrow donors with low doses of irradiation that would induce unique chromosome breaks in most hematopoietic cells but allow some cells to survive. Surviving cells displayed radiation-induced and repaired chromosomal breaks that marked each clonogenic (colony-initiating) hematopoietic cell.9 The researchers discovered that all dividing cells within a single spleen colony, which contained different types of blood cells, contained the same unique chromosomal marker. Each colony displayed its own unique chromosomal marker, seen in its dividing cells.9 Furthermore, when cells from a single spleen colony were re-injected into a second set of lethally-irradiated mice, donor-derived spleen colonies that contained the same unique chromosomal marker were often observed, indicating that these colonies had been regenerated from the same, single cell that had generated the first colony. Rarely, these colonies contained sufficient numbers of regenerative cells both to radioprotect secondary recipients (e.g., to prevent their deaths from radiation-induced blood cell loss) and to give rise to lymphocytes and myeloerythroid cells that bore markers of the donor-injected cells.10,11 These genetic marking experiments established the fact that cells that can both self-renew and generate most (if not all) of the cell populations in the blood must exist in bone marrow. At the time, such cells were called pluripotent HSCs, a term later modified to multipotent HSCs.12,13 However, identifying stem cells in retrospect by analysis of randomly chromosome-marked cells is not the same as being able to isolate pure populations of HSCs for study or clinical use.

Achieving this goal requires markers that uniquely define HSCs. Interestingly, the development of these markers, discussed below, has revealed that most of the early spleen colonies visible 8 to 10 days after injection, as well as many of the later colonies, visible at least 12 days after injection, are actually derived from progenitors rather than from HSCs. Spleen colonies formed by HSCs are relatively rare and tend to be present among the later colonies.14,15 However, these findings do not detract from Till and McCulloch's seminal experiments to identify HSCs and define these unique cells by their capacities for self-renewal and multilineage differentiation.

While much of the original work was, and continues to be, performed in murine model systems, strides have been made to develop assays to study human HSCs. The development of Fluorescence Activated Cell Sorting (FACS) has been crucial for this field (see Figure 2.2). This technique enables the recognition and quantification of small numbers of cells in large mixed populations. More importantly, FACS-based cell sorting allows these rare cells (1 in 2000 to less than 1 in 10,000) to be purified, resulting in preparations of near 100% purity. This capability enables the testing of these cells in various assays.

Figure 2.2. Enrichment and purification methods for hematopoietic stem cells. Upper panels illustrate column-based magnetic enrichment. In this method, the cells of interest are labeled with very small iron particles (A). These particles are bound to antibodies that only recognize specific cells. The cell suspension is then passed over a column through a strong magnetic field which retains the cells with the iron particles (B). Other cells flow through and are collected as the depleted negative fraction. The magnet is removed, and the retained cells are collected in a separate tube as the positive or enriched fraction (C). Magnetic enrichment devices exist both as small research instruments and large closed-system clinical instruments.

Lower panels illustrate Fluorescence Activated Cell Sorting (FACS). In this setting, the cell mixture is labeled with fluorescent markers that emit light of different colors after being activated by light from a laser. Each of these fluorescent markers is attached to a different monoclonal antibody that recognizes specific sets of cells (D). The cells are then passed one by one in a very tight stream through a laser beam (blue in the figure) in front of detectors (E) that determine which colors fluoresce in response to the laser. The results can be displayed in a FACS-plot (F). FACS-plots (see figures 3 and 4 for examples) typically show fluorescence levels per cell as dots or probability fields. In the example, four groups can be distinguished: Unstained, red-only, green-only, and red-green double labeling. Each of these groups, e.g., green fluorescence-only, can be sorted to very high purity. The actual sorting happens by breaking the stream shown in (E) into tiny droplets, each containing 1 cell, that then can be sorted using electric charges to move the drops. Modern FACS machines use three different lasers (that can activate different set of fluorochromes), to distinguish up to 8 to 12 different fluorescence colors and sort 4 separate populations, all simultaneously.

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2. Bone Marrow (Hematopoietic) Stem Cells [Stem Cell Information]

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Newswise HOUSTON (Dec. 10, 2013) A first-of-its-kind clinical trial studying two forms of stem cell treatments for children with cerebral palsy (CP) has begun at The University of Texas Health Science Center at Houston (UTHealth) Medical School.

The double-blinded, placebo-controlled studys purpose includes comparing the safety and effectiveness of banked cord blood to bone marrow stem cells. It is led by Charles S. Cox, Jr., M.D., the Childrens Fund, Inc. Distinguished Professor of Pediatric Surgery at the UTHealth Medical School and director of the Pediatric Trauma Program at Childrens Memorial Hermann Hospital. Co-principal investigator is Sean I. Savitz, M.D., professor and the Frank M. Yatsu, M.D., Chair in Neurology in the UTHealth Department of Neurology.

The study builds on Cox extensive research studying stem cell therapy for children and adults who have been admitted to Childrens Memorial Hermann and Memorial Hermann-Texas Medical Center after suffering a traumatic brain injury (TBI). Prior research, published in the March 2010 issue of Neurosurgery, showed that stem cells derived from a patients own bone marrow were safely used in pediatric patients with TBI. Cox is also studying cord blood stem cell treatment for TBI in a separate clinical trial.

A total of 30 children between the ages of 2 and 10 who have CP will be enrolled: 15 who have their own cord blood banked at Cord Blood Registry (CBR) and 15 without banked cord blood. Five in each group will be randomized to a placebo control group. Families must be able to travel to Houston for the treatment and follow-up visits at six, 12 and 24 months.

Parents will not be told if their child received stem cells or a placebo until the 12-month follow-up exam. At that time, parents whose children received the placebo may elect to have their child receive the stem cell treatment through bone marrow harvest or cord blood banked with CBR.

Collaborators for the study include CBR, Lets Cure CP, TIRR Foundation and Childrens Memorial Hermann Hospital. The study has been approved by the U.S. Food and Drug Administration.

Cerebral palsy is a group of disorders that affects the ability to move and maintain balance and posture, according to the Centers for Disease Control. It is caused by abnormal brain development or damage to the developing brain, which affects a persons control over muscles. Treatment includes medications, braces and physical, occupational and speech therapy.

For a list of inclusion and exclusion criteria for the trial, go to http://www.clinicaltrials.gov. For more information, call the toll-free number, 855-566-6273.

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UTHealth Researchers Study Stem Cell Treatments for Children with CP

Researchers in Sweden have successfully grown functioning neural tissues in lab, which has opened up significant new possibilities in medical science including new ways of treating cases of brain damage.

Scientists have already developed sophisticated techniques to grow tissues of other visceral organs such as kidney, liver, trachea, lymph nodes, and veins, and have even performed tissue transplantations in body for organ regeneration.

However, growing neural tissues in the lab is itself tricky as neurons are the most complex cells in our body, and imitating the functional biology of brain has been the most challenging task for scientists trying to unlock the mysteries of human body.

Neural tissues have been grown before in labs, but there is still a long way to go before researchers can achieve in vivo nerve regeneration and differentiation.

But Paolo Macchiarini and Silvia Baiguera at the Karolinska Institute in Stockholm may have identified a way forward.

Organic tissue is grown in a scaffold which replicates the protein-rich environment of tissues in the body, known as extracellular matrix (ECM). The in vitro scaffold thus provides nutrients and biochemical cues to the embedded stem cells to help them grow into differentiated cells.

The researchers contrived a gelatin scaffold with extracellular plasma from rat brain cells to replicate in vivo environment, and then lodged mesenchymal stem cells from another rat's bone marrow into the scaffold. The experiment was successful as the stem cells grew into differentiated neural cells in vitro.

The team believes that the bioengineering technique could be used for surgically treating neurodegenerative disorders and injuries.

Macchiarini hopes of using transplants of bioengineered tissue to replace parts of the brain tissues damaged by gunshots, concussions etc. and in conditions such as Parkinson's and Alzheimer's caused by death of brain cells.

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Scientists Grow Functioning Neural Cells in Lab Raising Hopes of Bio-engineered Brain

Dec. 9, 2013 at 10:17 AM ET

Two men who had hoped they might be cured of an HIV infection after getting bone marrow transplants for cancer got some bad news, doctors said Monday. The virus has come back.

The intense and life-threatening treatments for cancer appeared to have wiped the virus out, and the two men took a chance and, earlier this year, stopped taking the HIV drugs that were keeping the virus under control.

At first, no signs of the virus could be found. But their doctors, cautious after decades of fighting a tricky virus, didnt declare a cure.

Its disappointing, said Dr. Daniel Kuritzkes of Brigham and Womens Hospital in Boston, who worked with Dr. Timothy Henrich to treat and study the two men.

But its still taught us a great deal.

The case of the two men shows that even if you make HIV seemingly disappear, it can be hiding out in the body and can re-activate. It might be somewhere other than in blood cells, Henrich said. Other scientists suspect HIV might be able to hole up in organs or inside the intestines.

Through this research we have discovered the HIV reservoir is deeper and more persistent than previously known and that our current standards of probing for HIV may not be sufficient to inform us if long-term HIV remission is possible if antiretroviral therapy is stopped, Henrich said.

Both patients have resumed therapy and are currently doing well. Neither man wants to be named.

Henrich, Kuritzkes and colleagues had actively looked for HIV patients with leukemia or lymphoma who had received bone marrow stem cell transplants.

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AIDS virus comes back in men who hoped for cure

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New research suggests that outcomes for patients who have undergone stem cell transplants from unrelated or mismatched donors could be improved with the use of a drug called bortezomib, also known as velcade. This is according to a study presented at the annual meeting of the American Society of Hematology.

Stem cell transplants are treatments carried out in an attempt to cure some cancers affecting the body's bone marrow, such as leukemia, lymphoma and myeloma.

The treatment involves very high doses of chemotherapy (myeloablation) or whole body radiotherapy to clear a person's bone marrow and immune system of cancerous cells.

After this process, the killed cells are replaced with healthy stem cells through a drip that flows into a vein. These stem cells can be from the patient's own body or from a donor - preferably a sibling.

According to researchers from the Dana-Farber Cancer Institute who conducted the study, stem cells from unrelated or mismatched donors are likely to lead to worse patient outcomes following transplantation.

These patients tend to have a higher mortality rate as a result of the treatment and are more likely to experience graft-versus-host-disease (GVHD). This is a disease in which the transplanted cells attack the immune system of the recipient.

According to the researchers, recipients of mismatched donor transplants have a severe GVHD rate of 37%, a 1-year treatment-related mortality rate of 45%, and a 1-year overall survival rate of 43%.

Recipients of unrelated donor transplants have a severe GVHD rate of 28%, a 1-year treatment-related mortality rate of 36%, and a 1-year overall survival rate of 52%.

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Stem cell transplantation outcomes 'improved with new drug regime'

Bone marrow is the tissue comprising the center of large bones.

It is the place where new blood cells are produced.

Bone marrow contains two types of stem cells: hemopoietic (which can produce blood cells) and stromal (which can produce fat, cartilage and bone).

There are two types of bone marrow: red marrow (also known as myeloid tissue) and yellow marrow.

Red blood cells, platelets and most white blood cells arise in red marrow; some white blood cells develop in yellow marrow.

The color of yellow marrow is due to the much higher number of fat cells.

Both types of bone marrow contain numerous blood vessels and capillaries. At birth, all bone marrow is red.

With age, more and more of it is converted to the yellow type.

Adults have on average about 2.6kg (5.7lbs) of bone marrow, with about half of it being red.

Red marrow is found mainly in the flat bones such as hip bone, breast bone, skull, ribs, vertebrae and shoulder blades, and in the cancellous ("spongy") material at the proximal ends of the long bones femur and humerus.

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Bone marrow - Science Daily

A new study appearing in STEM CELLS Translational Medicine (SCTM) demonstrates the potential of a subset of stem cell called CD34+ in treating hard to heal bone fractures.

Durham, NC (PRWEB) December 04, 2013

A new study appearing in STEM CELLS Translational Medicine (SCTM) demonstrates the potential of a subset of stem cell called CD34+ in treating hard to heal bone fractures.

While most patients recover from broken bones with little or no complication, up to 10 percent experience fractures that wont heal. This can lead to a number of debilitating side effects, from infection to bone loss, and it can require extensive treatment involving multiple operations and prolonged hospitalization as well as long-term disability.

Regenerating broken bone using stem cells could offer an answer. Adult human peripheral blood CD34+ cells have been shown to contain an abundance of a type of stem cell called endothelial progenitor cells (EPCs) as well as hematopoietic stem cells, which give rise to all types of blood cells. As such, they could be good candidates for this therapy.

However, while other types of stem cells had been tested for their bone regeneration potential, the ability of CD34+ to do so had never been reported on before the phase I/II clinical study was published in the current SCTM. It was conducted by researchers at Kobe University Graduate School of Medicine, led by Tomoyuki Matsumoto, M.D., and Ryosuke Kuroda, M.D., members of the universitys department of orthopedic surgery and its Institute of Biomedical Research and Innovation (IBRI).

The study was designed to evaluate the safety, feasibility and efficacy of autologous and G-CSF-mobilized CD34+ cells in patients with non-healing breaks, breaks that had not healed in nine months, in their legs. (G-CSF is a drug that releases stem cells from the bone marrow into the blood.) Seven patients were treated with the stem cells after receiving bone grafts.

Bone union was successfully achieved in every case, confirmed as early as 16.4 weeks on average after treatment, Dr. Kuroda said.

Dr. Matsumoto added, Neither deaths nor life-threatening adverse events were observed during the one year follow-up after the cell therapy. These results suggest feasibility, safety and potential effectiveness of CD34+ cell therapy in patients with nonunion.

Atsuhiko Kawamoto, MD, Ph.D., a collaborator in IBRI, said, "Our team has been conducting translational research of CD34+ cell-based vascular regeneration therapy mainly in cardiovascular diseases. This promising outcome in bone fracture opens a new gate of the bone marrow-derived stem cell application to other fields of medicine."

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Hard to heal bone fractures could benefit from CD34+ stem cell ...

In the early 1980s, when the transplant act was written, the process was more demanding, involving anesthesia and the use of large, hollow needles to extract marrow from a donors hip. But today, more than two-thirds of marrow donations are done via apheresis. Blood is taken from a donors arm, the bone-marrow stem cells are filtered out, and the blood is then returned to the donor through a needle in the other arm.

The Ninth Circuit panel held that these filtered stem cells are merely components of blood no different from blood-derived plasma, platelets and clotting factors, for which donor compensation is allowed.

The strongest opposition to compensation comes from the National Marrow Donor Program, the Minneapolis-based nonprofit that maintains the nations largest donor registry. Michael Boo, the programs chief strategy officer, says of reimbursement, Is that what we want people to be motivated by?

The problem with this logic is that altruism has proven insufficient to motivate enough people to give marrow and, as a result, people die.

HHS is presumably under pressure from the National Marrow Donor Program. The department does not otherwise explain its proposed rule except to claim that compensation runs afoul of the transplant acts intent to ban commodification of human stem cells and to curb opportunities for coercion and exploitation, encourage altruistic donation and decrease the likelihood of disease transmission.

But how could such concerns plausibly apply to marrow stem cells and not to blood plasma? The process of collecting plasma is safe: No serious infection has been transmitted in plasma-derived products in nearly two decades, according to the Plasma Protein Therapeutics Association. Strenuous screening and testing in a robust regulatory environment, coupled with voluntary industry standards and sophisticated manufacturing processes, have created what has been called the safest blood product available today.

Constitutional violation

Outlawing compensation for stem blood cells but not mature blood cells might even violate the constitutional guarantee of equal protection of the law, according to Jeff Rowes, a lawyer at the Institute for Justice, which represented Flynn.

HHS should withdraw its proposal. Ideally, Congress should thwart future regulatory mischief by amending the National Organ Transplant Act to stipulate that marrow stem cells are not organs.

Each year, 2,000 to 3,000 Americans in need of marrow transplants die waiting for a match. Altruism is a virtue, but clearly it is not a dependable motive for marrow donation.

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Opinion: Don’t bar pay for bone-marrow donors : page 2 ...

November 28, 2013

By LAURAN NEERGAARD AP Medical Writer

WASHINGTON (AP) -- Could paying for bone marrow cells really boost the number of donors? The Obama administration is taking steps to block a federal court ruling that had opened a way to find out.

Buying or selling organs has long been illegal, punishable by five years in jail. The 1984 National Organ Transplantation Act that set the payment ban didn't just refer to solid organs -- it included bone marrow transplants, too.

Thousands of people with leukemia and other blood diseases are saved each year by bone marrow transplants. Thousands more, particularly minorities, still have trouble finding a genetically compatible match even though millions of volunteers have registered as potential donors under the current altruistic system.

A few years ago, the libertarian Institute for Justice sued the government to challenge that system. It argued that more people with rare marrow types might register to donate -- and not back out later if they're found to be a match -- if they had a financial incentive such as a scholarship paid by a nonprofit group.

Ultimately, a panel of the 9th U.S. Circuit Court of Appeals ruled that some, not all, marrow donors could be compensated -- citing a technological reason. Years ago, the only way to get marrow cells was to extract them from inside bone. Today, a majority of donors give marrow-producing cells through a blood-filtering process that's similar to donating blood plasma. Because it's legal to pay plasma donors, the December 2011 court ruling said marrow donors could be paid, too, as long as they give in that newer way.

"They're not even transplanting your bone marrow. They're transplanting these baby blood cells," said Jeff Rowes, an attorney with the Institute for Justice. It represented some families who'd had trouble finding donors, and was pushing for a study of compensation as a next step.

Not so fast, says the Obama administration. The government now has proposed a regulation to keep the ban intact by rewriting some legal definitions to clarify that it covers marrow-producing stem cells no matter how they're derived.

"It is not a matter of how you obtain it," said Shelley Grant of the Health Resources and Services Administration's transplant division. "Whether we obtain them through the marrow or the circulatory system, it is those stem cells that provide a potential cure."

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Gov't to keep ban on paying bone marrow donors | Minnesota ...

A bone marrow transplant is when special cells (called stem cells) that are normally found in the bone marrow are taken out, filtered, and given back either to the same person or to another person.

In diseases such as leukemia and aplastic anemia, the bone marrow is unhealthy. The purpose of a bone marrow transplant is to replace unhealthy stem cells withhealthy ones. This can treat or even cure the disease.

If a family member does not match the recipient, the National Marrow Donor Program Registry database can be searched for an unrelated individual whose tissue type is a close match. It is more likely that a donor who comes from the same racial or ethnic group as the recipient will have the same tissue traits. The chances of a minority person in the United States finding a registry match are lower than that of a white person (see article, Marrow Matches For Minorities Are Harder to Find).

If stem cells are collected by bone marrow harvest (much less likely), the donor will go to the operating room and while asleep under anesthesia, a needle will be inserted into either the hip or the breastbone to take out some bone marrow. After awakening, he/she may feel some pain where the needle was inserted.

Serious problems can occur during the time that the bone marrow is gone or very low. Infections are common, as is anemia, and low platelets in the blood can cause dangerous bleeding internally. Recipients often receive blood transfusions to treat these problems while they are waiting for the new stem cells to start growing.

When a person volunteers to be a donor, his/her particular blood tissue traits, as determined by a special blood test (histocompatibility antigen test), are recorded in the Registry. This "tissue typing" is different than a person's A, B, or O blood type. The Registry record also contains contact information for the donor, should a tissue type match be made.

Note: The author has been a registered donor since 1993.

Source:

"The Donation Procedure." Donor Information. Oct 2005. National Marrow Donor Program. 25 Jul 2007.

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Bone Marrow Transplants - How They Work - About.com Rare Diseases

Leukemia is a cancer of white blood cells, or leukocytes. Like other blood cells, leukocytes develop from somatic stem cells. Mature leukocytes are released into the bloodstream, where they work to fight off infections in our bodies.

Leukemia results when leukocytes begin to grow and function abnormally, becoming cancerous. These abnormal cells cannot fight off infection, and they interfere with the functions of other organs.

Successful treatment for leukemia depends on getting rid of all the abnormal leukocytes in the patient, allowing healthy ones to grow in their place. One way to do this is through chemotherapy, which uses potent drugs to target and kill the abnormal cells. When chemotherapy alone can't eliminate them all, physicians sometimes turn to bone marrow transplants.

In a bone marrow transplant, the patient's bone marrow stem cells are replaced with those from a healthy, matching donor. To do this, all of the patient's existing bone marrow and abnormal leukocytes are first killed using a combination of chemotherapy and radiation. Next, a sample of donor bone marrow containing healthy stem cells is introduced into the patient's bloodstream.

If the transplant is successful, the stem cells will migrate into the patient's bone marrow and begin producing new, healthy leukocytes to replace the abnormal cells.

New evidence suggests that bone marrow stem cells may be able to differentiate into cell types that make up tissues outside of the blood, such as liver and muscle. Scientists are exploring new uses for these stem cells that go beyond diseases of the blood.

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Stem Cells In Use - Learn Genetics

There are 3 possible sources of stem cells to use for transplants: bone marrow, the bloodstream (peripheral blood), and umbilical cord blood from newborns. Although bone marrow was the first source used in stem cell transplant, peripheral blood is used most often today.

Bone marrow is the spongy tissue in the center of bones. Its main job is to make blood cells that circulate in your body and immune cells that fight infection.

Bone marrow was the first source used for stem cell transplants because it has a rich supply of stem cells. The bones of the pelvis (hip) contain the most marrow and have large numbers of stem cells in them. For this reason, cells from the pelvic bone are used most often for a bone marrow transplant. Enough marrow must be removed to collect a large number of healthy stem cells.

For a bone marrow transplant, the donor gets general anesthesia (drugs are used to put the patient into a deep sleep so they dont feel pain). A large needle is put through the skin and into the back of the hip bone. The thick, liquid marrow is pulled out through the needle. This is repeated several times until enough marrow has been taken out (harvested). (For more on this, see the section called Whats it like to donate stem cells?)

The harvested marrow is filtered, stored in a special solution in bags, and then frozen. When the marrow is to be used, its thawed and then given just like a blood transfusion. The stem cells travel to the recipients bone marrow. There over time, they engraft or take and begin to make blood cells. Signs of the new blood cells usually can be measured in the patients blood tests in about 2 to 4 weeks.

Normally, few stem cells are found in the blood. But giving hormone-like substances called growth factors to stem cell donors a few days before the harvest causes their stem cells to grow faster and move from the bone marrow into the blood.

For a peripheral blood stem cell transplant, the stem cells are taken from blood. A very thin flexible tube (called a catheter) is put into one of the donors veins and attached to tubing that carries the blood to a special machine. The machine separates the blood, and keeps only the stem cells. The rest of the blood goes back to the donor. This takes several hours, and may need to be repeated for a few days to get enough stem cells. The stem cells are filtered, stored in bags, and frozen until the patient is ready for them. (For more on this, see the section called Whats it like to donate stem cells?)

After the patient is treated with chemo and/or radiation, the stem cells are given in an infusion much like a blood transfusion. The stem cells travel to the bone marrow, engraft, and then grow and make new, normal blood cells. The new cells are usually found in the patients blood a few days sooner than when bone marrow stem cells are used, usually in about 10 to 20 days.

Not everyone who needs an allogeneic stem cell transplant can find a well-matched donor among family members or among the people who have signed up to donate. For these patients, umbilical cord blood may be a source of stem cells. Around 30% of unrelated hematopoietic stem cell transplants are done with cord blood.

A large number of stem cells are normally found in the blood of newborn babies. After birth, the blood that is left behind in the placenta and umbilical cord (known as cord blood) can be taken and stored for later use in a stem cell transplant. The cord blood is frozen until needed.

More:
Sources of stem cells for transplant - American Cancer Society

Surgeon performs bone marrow harvest

The terms "Hodgkin's Disease," "Hodgkin's Lymphoma," and "Hodgkin Lymphoma" are used interchangeably throughout this site.

Bone Marrow Transplants (BMT) and Peripheral Blood Stem Cell Transplants (PBSCT) are emerging as mainstream treatment for many cancers, including Hodgkin's Disease and Medium/High grade aggressive)Non-Hodgkin's lymphoma.

BMTs have been used to treat lymphoma for more than 10 years, but until recently they were used mostly within clinical trials. Now BMTs are being used in conjunction with high doses of chemotherapy as a mainstream treatment.

When high doses of chemotherapy are planned, which can destroy the patients bone marrow, physicians will typically remove marrow from the patients bone before treatment and freeze it. After chemotherapy, the marrow is thawed and injected into a vein to replace destroyed marrow. This type of transplant is called an autologous transplant. If the transplanted marrow is from another person, it is called an allogeneic transplant.

In PBSCTs, another type of autologous transplant, the patient's blood is passed through a machine that removes the stem cells the immature cells from which all blood cells develop. This procedure is called apheresis and usually takes three or four hours over one or more days. After treatment to kill any cancer cells, the stem cells are frozen until they are transplanted back to the patient. Studies have shown that PBSCTs result in shorter hospital stays and are safer and more cost effective than BMTs.

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Stem Cell Transplants and Bone Marrow Transplant to Treat Lymphoma

Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains immature cells, called stem cells. The stem cells can develop into red blood cells, which carry oxygen throughout the body, white blood cells, which fight infections, and platelets, which help the to blood clot.

A bone marrow transplant is a procedure that replaces a person's faulty bone marrow stem cells. Doctors use these transplants to treat people with certain diseases, such as

Before you have a transplant, you need to get high doses of chemotherapy and possibly radiation. This destroys the faulty stem cells in your bone marrow. It also suppresses your body's immune system so that it won't attack the new stem cells after the transplant.

In some cases, you can donate your own bone marrow stem cells in advance. The cells are saved and then used later on. Or you can get cells from a donor. The donor might be a family member or unrelated person.

Bone marrow transplantation has serious risks. Some complications can be life-threatening. But for some people, it is the best hope for a cure or a longer life.

NIH: National Heart, Lung, and Blood Institute

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Bone Marrow Transplantation: MedlinePlus - National Library of ...

With more than 50 years of experience studying blood-forming stem cells called hematopoietic stem cells, scientists have developed sufficient understanding to actually use them as a therapy. Currently, no other type of stem cell, adult, fetal or embryonic, has attained such status. Hematopoietic stem cell transplants are now routinely used to treat patients with cancers and other disorders of the blood and immune systems. Recently, researchers have observed in animal studies that hematopoietic stem cells appear to be able to form other kinds of cells, such as muscle, blood vessels, and bone. If this can be applied to human cells, it may eventually be possible to use hematopoietic stem cells to replace a wider array of cells and tissues than once thought.

Despite the vast experience with hematopoietic stem cells, scientists face major roadblocks in expanding their use beyond the replacement of blood and immune cells. First, hematopoietic stem cells are unable to proliferate (replicate themselves) and differentiate (become specialized to other cell types) in vitro (in the test tube or culture dish). Second, scientists do not yet have an accurate method to distinguish stem cells from other cells recovered from the blood or bone marrow. Until scientists overcome these technical barriers, they believe it is unlikely that hematopoietic stem cells will be applied as cell replacement therapy in diseases such as diabetes, Parkinson's Disease, spinal cord injury, and many others.

Blood cells are responsible for constant maintenance and immune protection of every cell type of the body. This relentless and brutal work requires that blood cells, along with skin cells, have the greatest powers of self-renewal of any adult tissue.

The stem cells that form blood and immune cells are known as hematopoietic stem cells (HSCs). They are ultimately responsible for the constant renewal of bloodthe production of billions of new blood cells each day. Physicians and basic researchers have known and capitalized on this fact for more than 50 years in treating many diseases. The first evidence and definition of blood-forming stem cells came from studies of people exposed to lethal doses of radiation in 1945.

Basic research soon followed. After duplicating radiation sickness in mice, scientists found they could rescue the mice from death with bone marrow transplants from healthy donor animals. In the early 1960s, Till and McCulloch began analyzing the bone marrow to find out which components were responsible for regenerating blood [56]. They defined what remain the two hallmarks of an HSC: it can renew itself and it can produce cells that give rise to all the different types of blood cells (see Chapter 4. The Adult Stem Cell).

A hematopoietic stem cell is a cell isolated from the blood or bone marrow that can renew itself, can differentiate to a variety of specialized cells, can mobilize out of the bone marrow into circulating blood, and can undergo programmed cell death, called apoptosisa process by which cells that are detrimental or unneeded self-destruct.

A major thrust of basic HSC research since the 1960s has been identifying and characterizing these stem cells. Because HSCs look and behave in culture like ordinary white blood cells, this has been a difficult challenge and this makes them difficult to identify by morphology (size and shape). Even today, scientists must rely on cell surface proteins, which serve, only roughly, as markers of white blood cells.

Identifying and characterizing properties of HSCs began with studies in mice, which laid the groundwork for human studies. The challenge is formidable as about 1 in every 10,000 to 15,000 bone marrow cells is thought to be a stem cell. In the blood stream the proportion falls to 1 in 100,000 blood cells. To this end, scientists began to develop tests for proving the self-renewal and the plasticity of HSCs.

The "gold standard" for proving that a cell derived from mouse bone marrow is indeed an HSC is still based on the same proof described above and used in mice many years ago. That is, the cells are injected into a mouse that has received a dose of irradiation sufficient to kill its own blood-producing cells. If the mouse recovers and all types of blood cells reappear (bearing a genetic marker from the donor animal), the transplanted cells are deemed to have included stem cells.

These studies have revealed that there appear to be two kinds of HSCs. If bone marrow cells from the transplanted mouse can, in turn, be transplanted to another lethally irradiated mouse and restore its hematopoietic system over some months, they are considered to be long-term stem cells that are capable of self-renewal. Other cells from bone marrow can immediately regenerate all the different types of blood cells, but under normal circumstances cannot renew themselves over the long term, and these are referred to as short-term progenitor or precursor cells. Progenitor or precursor cells are relatively immature cells that are precursors to a fully differentiated cell of the same tissue type. They are capable of proliferating, but they have a limited capacity to differentiate into more than one cell type as HSCs do. For example, a blood progenitor cell may only be able to make a red blood cell (see Figure 5.1. Hematopoietic and Stromal Stem Cell Differentiation).

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5. Hematopoietic Stem Cells - NIH Stem Cell Information Home Page

Bone Marrow Cells & Tissue

AllCells is able to provide whole bone marrow aspirate and

collected from healthy individuals. These bone marrow products are available in fresh or frozen format.

The following bone marrow cells and tissue product types are available from AllCells:

Please view all of our Bone Marrow Products below.

Bone Marrow (BM) contains hematopoietic stem/progenitor cells, which are self-renewing, proliferating, and differentiating into multi-lineage blood cells. Multipotent, non-hematopoietic stem cells, such as bone marrow mesenchymal stem cells, can be isolated from human bone marrow as well. These non-hematopoietic, bone marrow stromal cells are capable of both self-renewal and differentiation into bone, cartilage, muscle, tendons, and fat. 100 mL of bone marrow cells and tissue is drawn into a 60cc syringe containing heparin (80 U/mL of BM) from the posterior iliac crest, at a maximum of eight separate sites. Whole bone marrow products are diluted with PBS. Please see our entire Bone Marrow Product inventory below.

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Bone Marrow Cells, Bone Marrow Stem Cells - AllCells.com