Bone marrow stem cells

Diseases such as aplastic anaemia, or infections (such as tuberculosis) can negatively impact the ability of the bone marrow to produce blood cells or platelets. Other diseases, such as leukaemia, also affect the progenitor/stem cells in the bone marrow and are diagnosed by a bone marrow biopsy where a sample of the tissue is taken using a large hollow needle inserted into the iliac crest (the pelvic bone). Harvesting bone marrow is usually done under general anaesthetic, although local anaesthetic is also a possibility.

Recent advances in stimulating and harvesting stem cells from the peripheral blood may mean that the invasiveness of bone marrow harvesting can be avoided for some donors and patients. Stimulatory pharmaceuticals, such as GM-CSF, and G-CSF, which drive the stem cells out of the bone marrow and into the peripheral circulation, can allow for a large yield of stem cells during apheresis. However, bone marrow stem cells have been found through research in the past five years or so to be able to differentiate into more cell types than previously thought. Mesenchymal stem cells from bone marrow have been successfully cultured to create beta-pancreatic cells, and neural cells, with possible ramifications for treatment of diabetes and neurodegenerative diseases. Clinical trials involving stem cell treatments for such conditions in humans remain theoretical however as there are a number of issues that need further investigation to confirm efficacy and safety.

The stem cells contained within bone marrow are of three types; haematopoietic stem cells, mesenchymal stem cells, and endothelial stem cells. Haematopoietic stem cells differentiate into both white and red blood cells, and platelets. These leukocytes, erythrocytes, and thrombocytes, respectively, play a role in immune function, oxygen transportation, and blood-clotting and are destroyed by chemotherapy for cancers such as leukaemia. This is why bone marrow transplants can mean the difference between life and death for someone suffering from such a disease as it is vital to replace and repopulate the bone marrow with stem cells that can then create new blood- and immune-forming cells.

Mesenchymal stem cells are also found in the bone marrow and are responsible for creating osteoblasts, chrondrocytes, and mycocytes, along with a number of other cell types. The location of these stem cells differs from that of the haematopoietic stem cells as they are usually central to the bone marrow, which makes it easier to extract specific populations of stem cells during a bone marrow aspiration procedure.

Bone marrow mesenchymal stem cells have also been found to differentiate into beta-pancreatic islet cells, with potential ramifications for treating those with diabetes (Moriscot, et al, 2005). Neural-like cells have also been cultured from bone marrow mesenchymal stem cells making the bone marrow a possible source for stem cell treatment of neurological disorders (Hermann, et al, 2006). More recent research appears to show that donor-heterogeneity (genetic differences between those donating the bone marrow) is at the heart of the variability in mesenchymal stem cells ability to differentiate to neural cells (Montzka, et al, 2009). This means that careful selection of donor stem cells would have to be carried out in order for treatment to be successful if the research ever displays clinical significance. Conditions such as spinal cord injury, Alzheimers Disease, and Multiple Sclerosis, may be able to be treated in the future using mesenchymal stem cells from bone marrow that were previously thought to only be able to produce bone and cartilage cell types.

Patients with leukaemia or other cancer are likely to be treated with radiation and/or chemotherapy. Both of these treatements kill the stem cells in the bone marrow to some degree and it is the effect that this has on the immune system that is responsible for many of the symptoms of chemotherapy and radiation sickness. In some cases, a patient with cancer may have bone marrow harvested and some stem cells stored prior to radiation treatment or chemotherapy. They then have their own stem cells infused after the cancer treatment in order to repopulate their immune system. This presents little risk of graft versus host disease which is a concern with, non-autologous, allograft bone marrow transplants. The use of a patients own stem cells is unlikely to be helpful in cases where an in-borne mutation of the blood and lymph system is present and such procedures are not usually performed in such cases.

Bone marrow transplantation from a donor source will normally require the destruction of the patients own bone marrow in a process called myeloablation. Patients who undergo myeloablation will lose their acquired immunity and are usually advised to undergo all vaccinations for diseases such as mumps, measles, rubella, and so on. Myeloablation also means that the patient has extremely low white blood cell (leukocyte) levels for a number of weeks as the bone marrow stem cells begin to create new blood and immune system cells. Patients undergoing this procedure are, therefore, extremely susceptible to infection and complication making bone marrow transplants only appropriate in life-threatening situations. Many patients will take antibiotics during this time in an attempt to avoid sepsis, infections, and septic shock. Some patients will be given immunosuppressant drugs to lower the risk of graft versus host disease and this can make them even more susceptible to infection.

It is also possible that the new stem cells do not engraft, which means that they do not begin to create new blood and immune-system cells at all. Peripheral blood stem cells harvested at the same time as bone marrow harvesting were found in one study to speed the recovery of the patients immune systems following myeloablation, thus reducing the risk if infection (Rabinowitz, et al, 1993). Peripheral blood stem cells do appear to be quicker in general at engrafting and they may become more widely involved in the treatment of diseases traditionally addressed through bone marrow transplants (Lewis, 2005).

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Bone Marrow Stem Cells – Stem Cell Treatment

Berlin, Jan 3 : German scientists have developed a prototype of artificial bone marrow, which can simplify the treatment of leukemia in a few years, Karlsruhe Institute of Technology (KIT) announced Friday.

Scientists from KIT, Max Planck Institute for Intelligent Systems in Stuttgart and the University of Tubingen have artificially recreated basic properties of the natural bone marrow in a laboratory, Xinhua reported.

The haematopoietic stem cells provide replenishment of red blood cells or immune cells, so they can be used for the treatment of leukemia, in a way that the diseased cells of the patient are replaced with healthy haematopoietic stem cells from a matched donor.

However, at present not every leukemia patient can find a matchable donor, so a simple solution to this problem would be to increase hematopoietic stem cells.

As the hematopoietic stem cells retain their stem cell properties only in their natural environment, the scientists need to create an environment that resembles the stem cell niche in the bone marrow.

To accomplish this goal, the German scientists created with synthetic polymer a porous structure that mimics the structure of the spongy bone in the area of the hematopoietic bone marrow.

In the artificial bone marrow, the researchers directed isolated hematopoietic stem cells freshly from umbilical cord blood and incubated them for several days.

Analyses with different methods showed that the cells actually proliferate in the newly developed artificial bone marrow.

Now the scientists can study the interactions between materials and stem cells in detail in the laboratory to find out how the behaviour of stem cell is influenced and controlled by synthetic materials.

This knowledge could help to realise an artificial stem cell niche for the targeted increase of stem cells to treat leukemia patients in 10 to 15 years.

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German scientists develop artificial bone marrow

London (PRWEB UK) 3 January 2014

Research on how to harness the potential use of stem cells for common conditions is a worldwide subject of scientific discovery spanning over 3 decades. Incredible results in laboratory experiments have been recorded in 2013 for areas such as tissue regeneration for coronary disease, diabetes, cancer, Parkinsons and Alzheimers disease. All stem cells, whether gathered from an early embryo, a foetus or an adult, have two key properties.

Stem cells have the ability to replicate themselves as needed and can generate any specialised cells that make up the tissues and organs of the body with proper direction. This opens up an exciting potential for the generation of therapies for repair and replacement of damaged and diseased tissues and organs, as models for the testing of new drugs and helping us to understand at a cellular level what goes wrong in many conditions. 1

Stem cells derived from bone marrow or fat has been found to improve recovery from stroke in experiments using rats. This study was published in BioMed Central's open access journal Stem Cell Research & Therapy early last year. Treatment with stem cells improved the amount of brain and nerve repair and the ability of the animals to complete behavioural tasks. Using stem cell therapy holds promise for patients but there are still many questions which need to be answered, regarding treatment protocols and which cell types to use. 2

Other areas in which stem cell transplants are already being successfully used in the clinic trials are for treatment for spinal lesions and the regeneration of epidermal surfaces and in leukaemia, where stem cells are replaced during stem cell-containing bone marrow transplants. 3 These treatments demonstrate the potential of stem cells and intensive research is being performed all over the world to improve our understanding of stem cells and how these can be used therapeutically for PD.

Recently published research by a team of scientists in Wales has shown early signs of being able to regenerate damaged heart tissue. By experimenting at Cardiff and Swansea university laboratories, a team of scientists working in the private sector hopes to develop new treatments for heart failure over the next five years.

In a statement for the research team Ajan Reginald said, "We've identified what we think is a very potent type of stem cell which is heart specific. The interim analysis looks very positive and very fortunately the study does show some signs of early regeneration. What the therapy does is reproduce more cells in large numbers to regenerate the part of the heart that is damaged. The first stage of clinical trial is now completed which was focused on safety. 4

Further research during the next five years will produce more alternative solutions to diseases which currently have treatment but no permanent cures for. 5

References

1.http://www.hta.gov.uk/_db/_documents/stem_cell_pack_200806170144.pdf 2.http://www.parkinsonsnsw.org.au/assets/attachments/research/Stem-Cells.pdf 3.http://stemcellres.com/content/4/1/11 4.http://www.bbc.co.uk/news/uk-wales-25560547 5.http://www.cell.com/stem-cell-reports/abstract/S2213-6711(13)00126-4#Summary

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Chemist Direct reports continued benefits of stem cell research for potential tissue regeneration

Clinical Policy Bulletin: Stem Cells for Bone Marrow Transplant

Aetna considers compatibility testing of prospective donors who are members of the immediate family (first-degree relatives, i.e., parents, siblings and children) and harvesting and short-term storage of peripheral stem cells or bone marrow from the identified donor medically necessary when an allogeneic bone marrow or peripheral stem cell transplant is authorized by Aetna.

Aetna considers umbilical cord blood stem cells an acceptable alternative to conventional bone marrow or peripheral stem cells for allogeneic transplant.

Aetna considers medically necessary the short-term storage of umbilical cord blood for a member with a malignancy undergoing treatment when there is a match. Note: The harvesting, freezing and/or storing umbilical cord blood of non-diseased persons for possible future use is not considered treatment of disease or injury. Such use is not related to the persons current medical care.

Notes:

When a covered family member of a newborn infant has a medically necessary indication for an allogeneic bone marrow transplant and wishes to use umbilical cord blood stem cells as an alternative, Aetna covers the testing of umbilical cord blood for compatibility for transplant under the potential recipients plan.

Performance of HLA typing and identification of a suitable donor does not, in and of itself, guarantee coverage of allogeneic bone marrow or peripheral stem cell transplantation. Medical necessity criteria and plan limitations and exclusions may apply.

See also the following CPBs related to bone marrow and peripheral stem cell transplantation:

According to the American Academy of Pediatrics (2007), cord blood transplantation has been shown to be curative in patients with a variety of serious diseases. Physicians should be familiar with the rationale for cord blood banking and with the types of cord blood banking programs available. Physicians consulted by prospective parents about cord blood banking can provide the following information:

Cord blood donation should be discouraged when cord blood stored in a bank is to be directed for later personal or family use, because most conditions that might be helped by cord blood stem cells already exist in the infant's cord blood (i.e., pre-malignant changes in stem cells). Physicians should be aware of the unsubstantiated claims of private cord blood banks made to future parents that promise to insure infants or family members against serious illnesses in the future by use of the stem cells contained in cord blood. Although not standard of care, directed cord blood banking should be encouraged when there is knowledge of a full sibling in the family with a medical condition (malignant or genetic) that could potentially benefit from cord blood transplantation.

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Stem Cells for Bone Marrow Transplant

A Vietnamese girl adopted by a Swiss family underwent a stem cell transplant last Friday, months after she was diagnosed with acute lymphoblastic leukemia.

Joon Gremillet, 18, is under special care at the Geneva General Hospital with visits restricted to protect her from infections, given that her immune system drops close to zero, according to a post on the blog site Help Joon, which was opened to look for a matching donor by her adoptive father Patrick Gremillet, a senior program coordinator at the United Nations Development Program.

Patrick received Joon from a maternity hospital in Hai Phong in northern Vietnam and she has grown up with the family, traveling through Laos, Thailand, US, Austria and France.

Joon, who started her university studies last year in Geneva, was diagnosed with leukemia last May.

She was hospitalized immediately and received chemotherapy before the search began for a bone marrow donor that considerably increases chances of survival.

The father said a donor was a stressful issue as Joon was adopted and there was little chance of finding a matching donor in her current community.

He said there are also few Asians, and Vietnamese in particular, who are enrolled in the international stem cell donor registry.

Fortunately, a compatible donor was found in November, although details are being kept confidential.

Patrick said the donors stem cells were infused into his daughter in a process that lasted nearly two hours.

He said Joon will have to wait for between ten to 30 days before the transplanted cells begin to circulate in her bones and gradually resume production of bone marrow and blood cells. If things go well, she can regain immunity after three months.

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A miracle and a clarion call for more

Four year old Hannah Day has spent most of her young life in and out of hospital.

She has Leukemia and its the second time in as many years that she is battling cancer.

She underwent 15 months of chemotherapy for a tumour in her stomach, but weeks later was diagnosed with Leukemia. Hannahs family says her only hope for survival is a stem-cell transplant, but neither her sister nor her parents are a perfect match, so theyre hoping a donor will be found. They set up a web page called Angels for Hannah to try and find a donor.

A stem-cell transplant is her last chance.

To become a stem-cell donor you can fill out a questionnaire online if youre between the ages of 17 and 35, and youll be sent a kit in the mail. A swab of your cheeks will reveal if youre a suitable donor. Once identified as a match, donors will undergo one of two procedures. Stem cells can be harvested from bone marrow under general anesthetic, or throughperipheral blood stem cell donation.

The donor does not experience pain during either procedure.

Our age criteria is 17 to 35 to register, saysMary Lynn Pride from Canadian Blood Services. So were really looking to those young people to step forward to provide an opportunity to help patients like Hannah who are in need. Were also asking young men to step forward because we do have a particular need for young men to register as they have been deemed as the optimal donor patients in need of transplant.

Pride says generally men produce a higher volume of stem cells for donation but also post-transplant there is better recovery for patients with a male donor over a female donor.

We do know that younger donors provide better post-transplant recovery for patients as well as the longevity of ensuring that they are on the registry longer to support patients in need, she says.

Canada currently has 326,000 people who are already registered as potential stem-cell donors. Hannah is one of 750 Canadians who are currently awaiting a stem-cell transplant.

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Stem-cell transplant needed for 4-year-old Hannah Day: How to help

Stem cell transplants are sometimes used to treat lymphoma patients who are in remission (that is, they seem to be disease-free after treatment) or who have had the cancer come back (relapse) during or after treatment.

In a stem cell transplant, doctors give higher doses of chemotherapy (chemo) than would normally be safe. Giving high-dose chemo destroys the bone marrow, which prevents new blood cells from being made. This could normally lead to life-threatening infections, bleeding, and other problems due to low blood cell counts. To get around this problem, after chemo (and sometimes radiation treatment) is finished, the patient gets an infusion of blood-forming stem cells to restore the bone marrow. Blood-forming stem cells are very early cells that can make new blood cells. They are different from embryonic stem cells.

There are 2 main types of stem cell transplants. The difference is the source of the blood-forming stem cells.

Autologous stem cell transplant: For this type of transplant, blood-forming stem cells from the patient's own blood or, less often, from the bone marrow, are removed, frozen, and stored until after treatment. Then the stored stem cells are thawed and given back to the patient through a vein. The cells enter the bloodstream and return to the bone, replacing the marrow and making new blood cells.

This is the most common type of transplant used to treat lymphoma, but it generally isn't an option if the lymphoma has spread to the bone marrow or blood. If that happens, it may be hard to get a stem cell sample with no lymphoma cells in it.

Donor (allogeneic) stem cell transplant: In this approach, the stem cells come from someone else usually a matched donor whose tissue type is very close to the patient's. The donor may be a brother or sister or someone not related to the patient. Sometimes umbilical cord stem cells are used.

This type of transplant is not used a lot in treating non-Hodgkin lymphoma (NHL) because it can have severe side effects that are especially hard for patients who are older or who have other medical problems. And it is often hard to find a matched donor.

"Mini transplant": Many older patients can't have a regular allogeneic transplant that uses high doses of chemo. But some may be able to have what is called a "mini transplant" (or a non-myeloablative transplant or reduced-intensity transplant). For this type of allogeneic transplant, lower doses of chemo and radiation are used so they do not destroy all the stem cells in the bone marrow. The patient is then given the donor stem cells. These cells enter the body and form a new immune system, which sees the cancer cells as foreign and attacks them (called a "graft-versus-lymphoma" effect).

Patients can often do a mini transplant as an outpatient. But this is not yet a standard part of the treatment for most types of lymphoma.

Stem cell transplant is a complex treatment, so it is important to have it done at a hospital where the staff has experience with the procedure. Some transplant programs may not have experience in certain transplants, especially those from unrelated donors.

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Bone marrow or peripheral blood stem cell transplant for non ...

It's the Christmas gift one little boys family thought they would never receive a life-saving transplant after a worldwide search for a donor.

But miraculously, two-year-old Gaurav Bains has finally had the operation he desperately needed.

His family have endured a torturous ordeal as the months counted down to a Christmas deadline to find a bone marrow donor with a 100 per cent match.

The young lad had always been ill after being born premature, but earlier this year, after a series of chest infections, he was diagnosed with Monosomy 7 Syndrome, a rare blood condition.

Then in the summer, his family was told his best chance of a healthy life would be if a donor was found before Christmas

Had a match not been found, Gauravs condition meant he would have been likely to develop an aggressive form of childhood leukaemia, which he may not have survived.

But thanks to a huge campaign, and the determination of his family, thousands of people signed up to the donation register from around the country and the world.

And this week the youngster finally had the operation that could save his life.

The whole procedure, which saw donated stem cells passed into his body, only took 90 minutes, and now his family, from Alexandra Road in Tipton, are optimistic.

Dad Sunny Bains, aged 31 and a shopkeeper, said: Everything went alright and he didnt have any side effects.

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Best Christmas ever as Gaurav gets the gift of life

Keith Leishman, a retired RCMP staff sergeant and former CSIS officer, was sent on a critical international mission this year but not the kind youd think.

It had nothing to so with detective work or espionage: Leishman completed a high-stakes medical mission as a volunteer bone marrow stem cell courier.

The 72-year-old South Surrey resident is one of a dozen retired Mounties recruited and trained by the Bruce Denniston Bone Marrow Society to make crucial deliveries of human tissue to B.C. patients awaiting life-saving treatments.

The Bone Marrow Courier Program was set up by the Society and Vancouver Coastal Health in 2012. Formerly, Vancouver General Hospital staff served as couriers, but as more treatments were performed, some staff were away 50 per cent of the year. And, it was costly.

Because of the delicate nature of human tissue transport, not just any volunteer would do. Yet retired Mounties have experience with stressful operations, understand the importance of securing evidence and confidentiality, and are accustomed to dealing calmly and authoritatively with security.

One of the advantages they see with RCMP officers is the experience they have with continuity of possession, Leishman explained. Just like you take a piece of evidence, once we take possession of those stem cells they cant leave our sight until we turn them over at the lab at VGH. There is a very strict protocol in place.

Deliveries must be made within 72 hours of removal from a donor, as the tissue starts to degrade. Samples must be kept at a precise temperature and in sight at all times even while navigating customs and airport security.

Leishman went on his first mission in mid-September, flying to Berlin to collect a sample. He secured it as his carry-on luggage, got it safely through customs but never through X-rays, which damage the material and completed his mission without incident. Others have faced flight delays, airline strikes and bad weather.

Volunteers often spend just 24 hours on the ground.

Its not a holiday, he said. You are focused on getting that package back to someone who is very ill. It could be someones last chance.

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Ex-Mounties serve as couriers for life-saving bone marrow stem cells

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 ...