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Bone marrow transplant: MedlinePlus Medical Encyclopedia

By NEVAGiles23

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.

Bone marrow is the soft, fatty tissue inside your bones. Stem cells are immature cells in the bone marrow that give rise to all of your blood cells.

There are three kinds of bone marrow transplants:

Before the transplant, chemotherapy, radiation, or both may be given. This may be done in two ways:

A stem cell transplant is done after chemotherapy and radiation is complete. The stem cells are delivered into your bloodstream usually through a tube called a central venous catheter. The process is similar to getting a blood transfusion. The stem cells travel through the blood into the bone marrow. Most times, no surgery is needed.

Donor stem cells can be collected in two ways:

A bone marrow transplant replaces bone marrow that either is not working properly or has been destroyed (ablated) by chemotherapy or radiation.

Your doctor may recommend a bone marrow transplant if you have:

A bone marrow transplant may cause the following symptoms:

Possible complications of a bone marrow transplant depend on many things, including:

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Adult Stem Cells Enhancer, From Fermented Biotechnology. – Video

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Adult Stem Cells Enhancer, From Fermented Biotechnology.
Consistently Increase of 50-100% Bone Marrow stem cells. This is most powerful Stem Cell Enhancer Consistently Increase 50-100%, From Fermented Biotechnology...

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Bone Marrow Transplants and Stem Cell Transplants for Cancer Treatment

By Dr. Matthew Watson

Stem cell transplants -- from bone marrow or other sources -- can be an effective treatment for people with certain forms of cancer, such as leukemia and lymphoma. Stem cell transplants are also used for multiple myeloma and neuroblastoma, and theyre being studied as a treatment for other cancers, too.

Why do cancer patients consider these transplants? While high doses of chemotherapy and radiation can effectively kill cancer cells, they have an unwanted side effect: They can also destroy the bone marrow, where blood cells are made.

Overview

Approximately 1.5 million new cases of cancer were expected to be diagnosed in the United States in 2009,[1] and that number is expected to rise in 2010.[2] Many patients diagnosed with cancer will eventually require support from a family caregiver. In fact, family caregivers form the foundation of the health care system in the United States, supporting advances in treatment such as multimodality treatment protocols given in outpatient and home settings.[3] Definition: Who Is the Caregiver? Also...

Read the Overview article > >

The purpose of a stem cell transplant or a bone marrow transplant is to replenish the body with healthy cells and bone marrow when chemotherapy and radiation are finished. After a successful transplant, the bone marrow will start to produce new blood cells. In some cases, the transplant can have an added benefit; the new blood cells will also attack and destroy any cancer cells that survived the initial treatment.

While you may have heard about embryonic stem cells in the news, the stem cells used in cancer treatment are different. Theyre called hematopoietic stem cells.

Whats special about these cells? Unlike most cells, these stem cells have the ability to divide and form new and different kinds of blood cells. Specifically, they can create oxygen-carrying red blood cells, infection-fighting white blood cells, and clot-forming platelets.

Most stem cells are in the bone marrow, a spongy tissue inside bone. Other stem cells -- called peripheral blood stem cells -- circulate in the blood. Both types can be used in stem cell transplants for cancer treatment.

While stem cell transplants may be lifesaving, theyre not the right treatment for everyone. The process can be difficult and tedious. Since younger people often do better with these treatments, some doctors limit stem cell transplants to those under age 60 or 70.

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Adult Stem Cell Enhancer by Dr. Riordan, Chinese subtitle. – Video

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Bone Marrow Diseases: MedlinePlus – U.S. National Library of Medicine

By Dr. Matthew Watson

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 the red blood cells that carry oxygen through your body, the white blood cells that fight infections, and the platelets that help with blood clotting.

If you have a bone marrow disease, there are problems with the stem cells or how they develop. Leukemia is a cancer in which the bone marrow produces abnormal white blood cells. With aplastic anemia, the bone marrow doesn't make red blood cells. Other diseases, such as lymphoma, can spread into the bone marrow and affect the production of blood cells. Other causes of bone marrow disorders include your genetic makeup and environmental factors.

Symptoms of bone marrow diseases vary. Treatments depend on the disorder and how severe it is. They might involve medicines, blood transfusions or a bone marrow transplant.

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Hematopoietic stem cell transplantation – Wikipedia, the free …

By JoanneRUSSELL25

Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. It is a medical procedure in the fields of hematology and oncology, most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia. In these cases, the recipient's immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease is a major complication of allogenic HSCT.

Hematopoietic stem cell transplantation remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As the survival of the procedure increases, its use has expanded beyond cancer, such as autoimmune diseases.[1][2]

Many recipients of HSCTs are multiple myeloma[3] or leukemia patients[4] who would not benefit from prolonged treatment with, or are already resistant to, chemotherapy. Candidates for HSCTs include pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia with defective stem cells, and also children or adults with aplastic anemia[5] who have lost their stem cells after birth. Other conditions[6] treated with stem cell transplants include sickle-cell disease, myelodysplastic syndrome, neuroblastoma, lymphoma, Ewing's sarcoma, desmoplastic small round cell tumor, chronic granulomatous disease and Hodgkin's disease. More recently non-myeloablative, or so-called "mini transplant," procedures have been developed that require smaller doses of preparative chemo and radiation. This has allowed HSCT to be conducted in the elderly and other patients who would otherwise be considered too weak to withstand a conventional treatment regimen.

A total of 50,417 first hematopoietic stem cell transplants were reported as taking place worldwide in 2006, according to a global survey of 1327 centers in 71 countries conducted by the Worldwide Network for Blood and Marrow Transplantation. Of these, 28,901 (57%) were autologous and 21,516 (43%) were allogenetic (11,928 from family donors and 9,588 from unrelated donors). The main indications for transplant were lymphoproliferative disorders (54.5%) and leukemias (33.8%), and the majority took place in either Europe (48%) or the Americas (36%).[7] In 2009, according to the world marrow donor association, stem cell products provided for unrelated transplantation worldwide had increased to 15,399 (3,445 bone marrow donations, 8,162 peripheral blood stem cell donations, and 3,792 cord blood units).[8]

Autologous HSCT requires the extraction (apheresis) of haematopoietic stem cells (HSC) from the patient and storage of the harvested cells in a freezer. The patient is then treated with high-dose chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population at the cost of partial or complete bone marrow ablation (destruction of patient's bone marrow function to grow new blood cells). The patient's own stored stem cells are then transfused into his/her bloodstream, where they replace destroyed tissue and resume the patient's normal blood cell production. Autologous transplants have the advantage of lower risk of infection during the immune-compromised portion of the treatment since the recovery of immune function is rapid. Also, the incidence of patients experiencing rejection (graft-versus-host disease) is very rare due to the donor and recipient being the same individual. These advantages have established autologous HSCT as one of the standard second-line treatments for such diseases as lymphoma.[9] However, for others such as Acute Myeloid Leukemia, the reduced mortality of the autogenous relative to allogeneic HSCT may be outweighed by an increased likelihood of cancer relapse and related mortality, and therefore the allogeneic treatment may be preferred for those conditions.[10] Researchers have conducted small studies using non-myeloablative hematopoietic stem cell transplantation as a possible treatment for type I (insulin dependent) diabetes in children and adults. Results have been promising; however, as of 2009[update] it was premature to speculate whether these experiments will lead to effective treatments for diabetes.[11]

Allogeneic HSCT involves two people: the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more loci of the HLA gene, and a perfect match at these loci is preferred. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely HLA matched sibling), syngeneic (a monozygotic or 'identical' twin of the patient - necessarily extremely rare since few patients have an identical twin, but offering a source of perfectly HLA matched stem cells) or unrelated (donor who is not related and found to have very close degree of HLA matching). Unrelated donors may be found through a registry of bone marrow donors such as the National Marrow Donor Program. People who would like to be tested for a specific family member or friend without joining any of the bone marrow registry data banks may contact a private HLA testing laboratory and be tested with a mouth swab to see if they are a potential match.[12] A "savior sibling" may be intentionally selected by preimplantation genetic diagnosis in order to match a child both regarding HLA type and being free of any obvious inheritable disorder. Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells. In general, by transfusing healthy stem cells to the recipient's bloodstream to reform a healthy immune system, allogeneic HSCTs appear to improve chances for cure or long-term remission once the immediate transplant-related complications are resolved.[13][14][15]

A compatible donor is found by doing additional HLA-testing from the blood of potential donors. The HLA genes fall in two categories (Type I and Type II). In general, mismatches of the Type-I genes (i.e. HLA-A, HLA-B, or HLA-C) increase the risk of graft rejection. A mismatch of an HLA Type II gene (i.e. HLA-DR, or HLA-DQB1) increases the risk of graft-versus-host disease. In addition a genetic mismatch as small as a single DNA base pair is significant so perfect matches require knowledge of the exact DNA sequence of these genes for both donor and recipient. Leading transplant centers currently perform testing for all five of these HLA genes before declaring that a donor and recipient are HLA-identical.

Race and ethnicity are known to play a major role in donor recruitment drives, as members of the same ethnic group are more likely to have matching genes, including the genes for HLA.[1]

To limit the risks of transplanted stem cell rejection or of severe graft-versus-host disease in allogeneic HSCT, the donor should preferably have the same human leukocyte antigens (HLA) as the recipient. About 25 to 30 percent of allogeneic HSCT recipients have an HLA-identical sibling. Even so-called "perfect matches" may have mismatched minor alleles that contribute to graft-versus-host disease.

In the case of a bone marrow transplant, the HSC are removed from a large bone of the donor, typically the pelvis, through a large needle that reaches the center of the bone. The technique is referred to as a bone marrow harvest and is performed under general anesthesia.

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Bone marrow – Wikipedia, the free encyclopedia

By Dr. Matthew Watson

This article is about the medical aspects of bone marrow in humans. For use of animal bone marrow in cuisine, see Bone marrow (food).

Bone marrow is the flexible tissue in the interior of bones. In humans, red blood cells are produced in the heads of long bones in a process known as hematopoiesis. On average, bone marrow constitutes 4% of the total body mass of humans; in an adult weighing 65 kilograms (143lb), bone marrow typically accounts for approximately 2.6 kilograms (5.7lb). The hematopoietic component of bone marrow produces approximately 500 billion blood cells per day, which use the bone marrow vasculature as a conduit to the body's systemic circulation.[1] Bone marrow is also a key component of the lymphatic system, producing the lymphocytes that support the body's immune system.[2]

Bone marrow transplants can be conducted to treat severe diseases of the bone marrow, including certain forms of cancer. Additionally, bone marrow stem cells have been successfully transformed into functional neural cells,[3] and can also potentially be used to treat illnesses such as inflammatory bowel disease[4] and, in some cases, HIV.[5][6]

The two types of bone marrow are medulla ossium rubra (red marrow), which consists mainly of hematopoietic tissue, and medulla ossium flava (yellow marrow), which is mainly made up of fat cells. Red blood cells, platelets and most white blood cells arise in red marrow. 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; only around half of adult bone marrow is red. Red marrow is found mainly in the flat bones, such as the pelvis, sternum, cranium, ribs, vertebrae and scapulae, and in the cancellous ("spongy") material at the epiphyseal ends of long bones such as the femur and humerus. Yellow marrow is found in the medullary cavity, the hollow interior of the middle portion of long bones. In cases of severe blood loss, the body can convert yellow marrow back to red marrow to increase blood cell production.

The stroma of the bone marrow is all tissue not directly involved in the marrow's primary function of hematopoiesis. Yellow bone marrow makes up the majority of bone marrow stroma, in addition to smaller concentrations of stromal cells located in the red bone marrow. Though not as active as parenchymal red marrow, stroma is indirectly involved in hematopoiesis, since it provides the hematopoietic microenvironment that facilitates hematopoiesis by the parenchymal cells. For instance, they generate colony stimulating factors, which have a significant effect on hematopoiesis. Cell types that constitute the bone marrow stroma include:

The blood vessels of the bone marrow constitute a barrier, inhibiting immature blood cells from leaving the marrow. Only mature blood cells contain the membrane proteins required to attach to and pass the blood vessel endothelium. Hematopoietic stem cells may also cross the bone marrow barrier, and may thus be harvested from blood.

The bone marrow stroma contains mesenchymal stem cells (MSCs),[7] also known as marrow stromal cells. These are multipotent stem cells that can differentiate into a variety of cell types. MSCs have been shown to differentiate, in vitro or in vivo, into osteoblasts, chondrocytes, myocytes, adipocytes and beta-pancreatic islets cells. MSCs can also transdifferentiate into neuronal cells.[3]

In addition, the bone marrow contains hematopoietic stem cells, which give rise to the three classes of blood cells that are found in the circulation: white blood cells (leukocytes), red blood cells (erythrocytes), and platelets (thrombocytes).[7]

Biological compartmentalization is evident within the bone marrow, in that certain cell types tend to aggregate in specific areas. For instance, erythrocytes, macrophages, and their precursors tend to gather around blood vessels, while granulocytes gather at the borders of the bone marrow.

The red bone marrow is a key element of the lymphatic system, being one of the primary lymphoid organs that generate lymphocytes from immature hematopoietic progenitor cells.[2] The bone marrow and thymus constitute the primary lymphoid tissues involved in the production and early selection of lymphocytes. Furthermore, bone marrow performs a valve-like function to prevent the backflow of lymphatic fluid in the lymphatic system.

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Bone Marrow Transplantation and Peripheral Blood Stem Cell …

By Dr. Matthew Watson

What are bone marrow and hematopoietic stem cells?

Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells known as hematopoietic or blood-forming stem cells. (Hematopoietic stem cells are different from embryonic stem cells. Embryonic stem cells can develop into every type of cell in the body.) Hematopoietic stem cells divide to form more blood-forming stem cells, or they mature into one of three types of blood cells: white blood cells, which fight infection; red blood cells, which carry oxygen; and platelets, which help the blood to clot. Most hematopoietic stem cells are found in the bone marrow, but some cells, called peripheral blood stem cells (PBSCs), are found in the bloodstream. Blood in the umbilical cord also contains hematopoietic stem cells. Cells from any of these sources can be used in transplants.

What are bone marrow transplantation and peripheral blood stem cell transplantation?

Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. There are three types of transplants:

Why are BMT and PBSCT used in cancer treatment?

One reason BMT and PBSCT are used in cancer treatment is to make it possible for patients to receive very high doses of chemotherapy and/or radiation therapy. To understand more about why BMT and PBSCT are used, it is helpful to understand how chemotherapy and radiation therapy work.

Chemotherapy and radiation therapy generally affect cells that divide rapidly. They are used to treat cancer because cancer cells divide more often than most healthy cells. However, because bone marrow cells also divide frequently, high-dose treatments can severely damage or destroy the patients bone marrow. Without healthy bone marrow, the patient is no longer able to make the blood cells needed to carry oxygen, fight infection, and prevent bleeding. BMT and PBSCT replace stem cells destroyed by treatment. The healthy, transplanted stem cells can restore the bone marrows ability to produce the blood cells the patient needs.

In some types of leukemia, the graft-versus-tumor (GVT) effect that occurs after allogeneic BMT and PBSCT is crucial to the effectiveness of the treatment. GVT occurs when white blood cells from the donor (the graft) identify the cancer cells that remain in the patients body after the chemotherapy and/or radiation therapy (the tumor) as foreign and attack them. (A potential complication of allogeneic transplants called graft-versus-host disease is discussed in Questions 5 and 14.)

What types of cancer are treated with BMT and PBSCT?

BMT and PBSCT are most commonly used in the treatment of leukemia and lymphoma. They are most effective when the leukemia or lymphoma is in remission (the signs and symptoms of cancer have disappeared). BMT and PBSCT are also used to treat other cancers such as neuroblastoma (cancer that arises in immature nerve cells and affects mostly infants and children) and multiple myeloma. Researchers are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment of various types of cancer.

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Avascular necrosis treatment with bone marrow stem cells. – Video

By Dr. Matthew Watson


Avascular necrosis treatment with bone marrow stem cells.
Avascular necrosis treatment with stem cells from bone marrow. Visit http://www.blog.hipsurgery.in to get details of types of treatment. Visit http://www.hipsurgery...

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Bone Marrow Stem Cells Help Cerebral Palsy – Andrew’s Testimony – Video

By raymumme


Bone Marrow Stem Cells Help Cerebral Palsy - Andrew #39;s Testimony
Watch Andrew #39;s Testimonial on how adult bone marrow stem cells helped him and his cerebral palsy. Stem cells are helping cerebral palsy patients today includ...

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Type 2 diabetes patients transplanted with own bone marrow stem cells reduces insulin use

By JoanneRUSSELL25

Public release date: 28-Jun-2013 [ | E-mail | Share ]

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

Putnam Valley, NY. (June 28 2013) A study carried out in India examining the safety and efficacy of self-donated (autologous), transplanted bone marrow stem cells in patients with type 2 diabetes (TD2M), has found that patients receiving the transplants, when compared to a control group of TD2M patients who did not receive transplantation, required less insulin post-transplantation.

The study appears as an early e-publication for the journal Cell Transplantation, and is now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/pre-prints/ct0920bhansali.

"There is growing interest in the scientific community for cellular therapies that use bone marrow-derived cells for the treatment of type 2 diabetes mellitus and its complications," said study corresponding author Anil Bhansali, PhD professor and head of the Endocrinology Department at the Post Graduate Institute of Medical Education in Chandrigarh, India. "But the potential of stem cell therapy for this disease is yet to be fully explored."

While there is growing interest in using stem cell transplantation to treat TD2M, few studies have examined the utility of bone marrow-derived stem cells. By experimenting with bone marrow-derived stem cells, the researchers sought to exploit the rich source of stem cells in bone marrow.

Their study aimed at evaluating the efficacy and safety of autologous bone marrow-derived stem cell transplantation in patients with T2DM and who also had good glycemic control. Good glycemic control emerged as an important factor in the transplantation group and in the non-transplanted control group.

Cell transplantation had a significant impact on the patients in this study as those administered cells demonstrated a significant reduction in insulin requirement. A significantly smaller reduction in the insulin requirement of the control group was also observed but a "repeated emphasis on life style modification" was believed to be a contributing factor in this effect.

According to Dr. Bhansali, the strength of their study included the inclusion of a homogenous patient population with T2DM which exhibited good glycemic control, and the presence of a similar control group that did not get cell transplants.

"The efficacy and safety of stem cell therapy needs to be established in a greater number of patients and with a longer duration follow-up," concluded Bhansali and his co-authors. "The data available so far from animal and human studies is encouraging, however, it has enormous limitations."

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bone marrow stem cells used for back pain – Video

By Dr. Matthew Watson


bone marrow stem cells used for back pain
Brenda Goodman writing in Healthday reported, "Medical researchers are trying a new treatment for low back pain. Their hope is that harvesting and then re-in...

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A Different View on Bone Marrow Stem Cells – Video

By JoanneRUSSELL25


A Different View on Bone Marrow Stem Cells
HSCI Principal Faculty member Les E. Silberstein, MD, details how new imaging technologies allowed his laboratory to discover that bone marrow stem cells are located near blood vessels, but...

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Scientists find antibody that transforms bone marrow stem cells directly into brain cells

By NEVAGiles23

Public release date: 22-Apr-2013 [ | E-mail | Share ]

Contact: Mika Ono mikaono@scripps.edu 858-784-2052 Scripps Research Institute

LA JOLLA, CA April 22, 2013 In a serendipitous discovery, scientists at The Scripps Research Institute (TSRI) have found a way to turn bone marrow stem cells directly into brain cells.

Current techniques for turning patients' marrow cells into cells of some other desired type are relatively cumbersome, risky and effectively confined to the lab dish. The new finding points to the possibility of simpler and safer techniques. Cell therapies derived from patients' own cells are widely expected to be useful in treating spinal cord injuries, strokes and other conditions throughout the body, with little or no risk of immune rejection.

"These results highlight the potential of antibodies as versatile manipulators of cellular functions," said Richard A. Lerner, the Lita Annenberg Hazen Professor of Immunochemistry and institute professor in the Department of Cell and Molecular Biology at TSRI, and principal investigator for the new study. "This is a far cry from the way antibodies used to be thought ofas molecules that were selected simply for binding and not function."

The researchers discovered the method, reported in the online Early Edition of the Proceedings of the National Academy of Sciences the week of April 22, 2013, while looking for lab-grown antibodies that can activate a growth-stimulating receptor on marrow cells. One antibody turned out to activate the receptor in a way that induces marrow stem cellswhich normally develop into white blood cellsto become neural progenitor cells, a type of almost-mature brain cell.

Nature's Toolkit

Natural antibodies are large, Y-shaped proteins produced by immune cells. Collectively, they are diverse enough to recognize about 100 billion distinct shapes on viruses, bacteria and other targets. Since the 1980s, molecular biologists have known how to produce antibodies in cell cultures in the laboratory. That has allowed them to start using this vast, target-gripping toolkit to make scientific probes, as well as diagnostics and therapies for cancer, arthritis, transplant rejection, viral infections and other diseases.

In the late 1980s, Lerner and his TSRI colleagues helped invent the first techniques for generating large "libraries" of distinct antibodies and swiftly determining which of these could bind to a desired target. The anti-inflammatory antibody Humira, now one of the world's top-selling drugs, was discovered with the benefit of this technology.

Last year, in a study spearheaded by TSRI Research Associate Hongkai Zhang, Lerner's laboratory devised a new antibody-discovery techniquein which antibodies are produced in mammalian cells along with receptors or other target molecules of interest. The technique enables researchers to determine rapidly not just which antibodies in a library bind to a given receptor, for example, but also which ones activate the receptor and thereby alter cell function.

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Scripps Research Institute Scientists Find Antibody that Transforms Bone Marrow Stem Cells Directly into Brain Cells

By raymumme

LA JOLLA, Calif., April 22, 2013 /PRNewswire-USNewswire/ -- In a serendipitous discovery, scientists at The Scripps Research Institute (TSRI) have found a way to turn bone marrow stem cells directly into brain cells.

Current techniques for turning patients' marrow cells into cells of some other desired type are relatively cumbersome, risky and effectively confined to the lab dish. The new finding points to the possibility of simpler and safer techniques. Cell therapies derived from patients' own cells are widely expected to be useful in treating spinal cord injuries, strokes and other conditions throughout the body, with little or no risk of immune rejection.

"These results highlight the potential of antibodies as versatile manipulators of cellular functions," said Richard A. Lerner , the Lita Annenberg Hazen Professor of Immunochemistry and institute professor in the Department of Cell and Molecular Biology at TSRI, and principal investigator for the new study. "This is a far cry from the way antibodies used to be thought ofas molecules that were selected simply for binding and not function."

The researchers discovered the method, reported in the online Early Edition of the Proceedings of the National Academy of Sciences the week of April 22, 2013, while looking for lab-grown antibodies that can activate a growth-stimulating receptor on marrow cells. One antibody turned out to activate the receptor in a way that induces marrow stem cellswhich normally develop into white blood cellsto become neural progenitor cells, a type of almost-mature brain cell.

Nature's Toolkit

Natural antibodies are large, Y-shaped proteins produced by immune cells. Collectively, they are diverse enough to recognize about 100 billion distinct shapes on viruses, bacteria and other targets. Since the 1980s, molecular biologists have known how to produce antibodies in cell cultures in the laboratory. That has allowed them to start using this vast, target-gripping toolkit to make scientific probes, as well as diagnostics and therapies for cancer, arthritis, transplant rejection, viral infections and other diseases.

In the late 1980s, Lerner and his TSRI colleagues helped invent the first techniques for generating large "libraries" of distinct antibodies and swiftly determining which of these could bind to a desired target. The anti-inflammatory antibody Humira, now one of the world's top-selling drugs, was discovered with the benefit of this technology.

Last year, in a study spearheaded by TSRI Research Associate Hongkai Zhang, Lerner's laboratory devised a new antibody-discovery techniquein which antibodies are produced in mammalian cells along with receptors or other target molecules of interest. The technique enables researchers to determine rapidly not just which antibodies in a library bind to a given receptor, for example, but also which ones activate the receptor and thereby alter cell function.

Lab Dish in a Cell

For the new study, Lerner laboratory Research Associate Jia Xie and colleagues modified the new technique so that antibody proteins produced in a given cell are physically anchored to the cell's outer membrane, near its target receptors. "Confining an antibody's activity to the cell in which it is produced effectively allows us to use larger antibody libraries and to screen these antibodies more quickly for a specific activity," said Xie. With the improved technique, scientists can sift through a library of tens of millions of antibodies in a few days.

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Scripps Research Institute Scientists Find Antibody that Transforms Bone Marrow Stem Cells Directly into Brain Cells

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Diabetes distresses bone marrow stem cells by damaging their microenvironment

By Dr. Matthew Watson

Jan. 31, 2013 New research has shown the presence of a disease affecting small blood vessels, known as microangiopathy, in the bone marrow of diabetic patients. While it is well known that microangiopathy is the cause of renal damage, blindness and heart attacks in patients with diabetes, this is the first time that a reduction of the smallest blood vessels has been shown in bone marrow, the tissue contained inside the bones and the main source of stem cells.

These precious cells not only replace old blood cells but also exert an important reparative function after acute injuries and heart attacks. The starvation of bone marrow as a consequence of microangiopathy can lead to a less efficient healing in diabetic patients. Also, stem cells from a patient's bone marrow are the most used in regenerative medicine trials to mend hearts damaged by heart attacks. Results from this study highlight an important deficit in stem cells and supporting microenvironment that can reduce stem cells' therapeutic potential in diabetic patients.

The research team, led by Professor Paolo Madeddu, Chair of Experimental Cardiovascular Medicine in the School of Clinical Sciences and Bristol Heart Institute at the University of Bristol, investigated the effect of diabetes on bone marrow stem cells and the nurturing of small blood vessels in humans.

The new study, published in the American Heart Association journal Circulation Research, was funded by the British Heart Foundation (BHF).

The researchers have shown a profound remodelling of the marrow, which shows shortage of stem cells and surrounding vessels mainly replaced by fat, especially in patients with a critical lack of blood supply to a tissue (ischaemia). This means that, as peripheral vascular complications progress, more damage occurs in the marrow. In a vicious cycle, depletion of bone marrow stem cells worsens the consequences of peripheral ischaemia.

Investigation of underpinning mechanisms revealed that exposure of bone marrow stem cells to the high glucose level typical of diabetes mellitus impacts on "microRNAs," which are tiny RNA molecules controlling gene expression and hence biological functions. In particular, microRNA-155, that normally controls the production of stem cells, becomes dramatically reduced in bone marrow cells exposed to high glucose. Diabetes-induced deficits are corrected by reintroducing microRNA-155 in human stem cells. The authors foresee that microRNAs could be used to regain proper stem cells number in diabetes and fix stem cells before reintroduction into a patient's body.

Professor Paolo Madeddu said: "Our study draws attention to the bone marrow as a primary target of diabetes-induced damage. The research suggests that the severity of systemic vascular disease has an impact on bone marrow causing a precocious senescence of stem cells. More severe bone marrow pathologies can cause, or contribute to, cardiovascular disease and lead to worse outcomes after a heart attack, through the shortage of vascular regenerative cells. Clinical evidence indicates that achieving a good control of glucose levels is fundamental to prevent vascular complications, but is less effective in correcting microangiopathy. We need to work hard to find new therapies for mending damaged microvessels."

Professor Costanza Emanueli, Chair of Vascular Pathology and Regeneration at the University of Bristol and co-author of the paper, added: "MicroRNAs represent an attractive means to repair the marrow damage and generate "better" stem cells for regenerative medicine applications. We are working at protocols using microRNA targeting for enhancing the therapeutic potential of stem cells before their transplantation to cure heart and limb ischaemia, which are often associated with diabetes mellitus. More work is, however, necessary before using this strategy in patients."

The findings advance the current understanding of pathological mechanisms leading to collapse of the vascular niche and reduced availability of regenerative cells. The data provides a key for interpretation of diabetes-associated defect in stem cell mobilisation following a heart attack. In addition, the research reveals a new molecular mechanism that could in the future become the target of specific treatments to alleviate vascular complications in patients with diabetes.

Professor Jeremy Pearson, Associate Medical Director at the BHF said: "Professor Madeddu and his team have shown for the first time that the bone marrow in patients with diabetes can't release stem cells which are important for the repair of blood vessel damage commonly found in people with the disease.

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Diabetes distresses bone marrow stem cells by damaging their microenvironment

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“Fountain of Youth” technique rejuvenates aging stem cells – Study moves scientists one step closer to creating …

By JoanneRUSSELL25

Study moves scientists one step closer to creating youthful heart patches from old cells

TORONTO, ON A new method of growing cardiac tissue is teaching old stem cells new tricks. The discovery, which transforms aged stem cells into cells that function like much younger ones, may one day enable scientists to grow cardiac patches for damaged or diseased hearts from a patients own stem cellsno matter what age the patientwhile avoiding the threat of rejection.

Stem cell therapies involving donated bone marrow stem cells run the risk of patient rejection in a portion of the population, argues Milica Radisic, Canada Research Chair in Functional Cardiovascular Tissue Engineering at the Institute of Biomaterials and Biomedical Engineering (IBBME) and Associate Professor in the Department of Chemical Engineering and Applied Chemistry at the University of Toronto.

One method of avoiding the risk of rejection has been to use cells derived from a patients own body. But until now, clinical trials of this kind of therapy using elderly patients own cells have not been a viable option, since aged cells tend not to function as well as cells from young patients.

Its a problem that Radisic and her co-researcher, Dr. Ren-Ke Li, think they might have an answer for: by creating the conditions for a fountain of youth reaction within a tissue culture.

Li holds the Canada Research Chair in Cardiac Regeneration and is a Professor in the Division of Cardiovascular Surgery, cross-appointed to IBBME. He is also a Senior Scientist at the Toronto General Research Institute.

Radisic and Li first create a micro-environment that allows heart tissue to grow, with stem cells donated from elderly patients at the Toronto General Hospital.

The cell cultures are then infused with a combination of growth factorscommon factors that cause blood vessel growth and cell proliferationpositioned in such a way within the porous scaffolding that the cells are able to be stimulated by these factors.

Dr. Li and his team then tracked the molecular changes in the tissue patch cells.

We saw certain aging factors turned off, states Li, citing the levels of two molecules in particular, p16 and RGN, which effectively turned back the clock in the cells, returning them to robust and healthy states.

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“Fountain of Youth” technique rejuvenates aging stem cells - Study moves scientists one step closer to creating ...

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Stem cell discovery may revive damaged heart

By raymumme

Stem cell discovery may revive damaged heart

(IANS) / 29 November 2012

A new discovery that tricks aging stem cells into rejuvenating mode could enable scientists to create youthful patches for damaged or diseased hearts and heal them, according to a Canadian study.

The breakthrough may enable scientists to create such life giving patches from a patients own stem cells - regardless of the patients age - while avoiding the threat of rejection, the study claims.

Stem cell therapies involving donated bone marrow stem cells run the risk of patient rejection in a portion of the population, argues Milica Radisic, associate professor of chemical engineering and applied chemistry at the University of Toronto, the Journal of the American College of Cardiology reports.

One method of avoiding such a risk has been to use cells derived from a patients own body. But until now, clinical trials of this kind of therapy using elderly patients own cells have not been a viable option, since aged cells tend not to function as well as cells from young patients, according to a Toronto statement.

If you want to treat these people with their own cells, how do you do this? asks Radisic. Its a problem that Radisic and co-researcher Ren-Ke Li think they might have an answer for: by creating the conditions for a fountain of youth reaction within a tissue culture. Li is a professor in the division of cardiovascular surgery.

Radisic and Li first create a micro-environment that allows heart tissue to grow, with stem cells donated from elderly patients at the Toronto General Hospital, where Li works.

Li and his team then tracked the molecular changes in the tissue patch cells. We saw certain aging factors turned off, states Li, citing the levels of two molecules in particular, p16 and (regucalcin) RGN, which effectively turned back the clock in the cells, returning them to robust and states.

Its very exciting research, says Radisic, who was named one of the top innovators under 35 by MIT in 2008 and winner of the 2012 Young Engineers Canada award.

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Stem cell discovery may revive damaged heart

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'Fountain of youth' technique rejuvenates aging stem cells

By NEVAGiles23

ScienceDaily (Nov. 27, 2012) A new method of growing cardiac tissue is teaching old stem cells new tricks. The discovery, which transforms aged stem cells into cells that function like much younger ones, may one day enable scientists to grow cardiac patches for damaged or diseased hearts from a patient's own stem cells -- no matter what age the patient -- while avoiding the threat of rejection.

Stem cell therapies involving donated bone marrow stem cells run the risk of patient rejection in a portion of the population, argues Milica Radisic, Canada Research Chair in Functional Cardiovascular Tissue Engineering at the Institute of Biomaterials and Biomedical Engineering (IBBME) and Associate Professor in the Department of Chemical Engineering and Applied Chemistry at the University of Toronto.

One method of avoiding the risk of rejection has been to use cells derived from a patient's own body. But until now, clinical trials of this kind of therapy using elderly patients' own cells have not been a viable option, since aged cells tend not to function as well as cells from young patients.

"If you want to treat these people with their own cells, how do you do this?"

It's a problem that Radisic and her co-researcher, Dr. Ren-Ke Li, think they might have an answer for: by creating the conditions for a 'fountain of youth' reaction within a tissue culture.

Li holds the Canada Research Chair in Cardiac Regeneration and is a Professor in the Division of Cardiovascular Surgery, cross-appointed to IBBME. He is also a Senior Scientist at the Toronto General Research Institute.

Radisic and Li first create a "micro-environment" that allows heart tissue to grow, with stem cells donated from elderly patients at the Toronto General Hospital.

The cell cultures are then infused with a combination of growth factors -- common factors that cause blood vessel growth and cell proliferation -- positioned in such a way within the porous scaffolding that the cells are able to be stimulated by these factors.

Dr. Li and his team then tracked the molecular changes in the tissue patch cells. "We saw certain aging factors turned off," states Li, citing the levels of two molecules in particular, p16 and RGN, which effectively turned back the clock in the cells, returning them to robust and healthy states.

"It's very exciting research," says Radisic, who was named one of the top innovators under 35 by MIT in 2008 and winner of the 2012 Young Engineers Canada award.

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'Fountain of youth' technique rejuvenates aging stem cells

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Bone Tissue Engineering Study Led by Ghent University Improves Treatment of Bone Deficits Using Cryo-Save Stem Cells

By raymumme

ZUTPHEN, the Netherlands, November 20, 2012 /PRNewswire/ --

Ghent University and Cryo-Saves collaboration overcomes the restrictions encountered in bone tissue engineering of large size bone grafts. This traditional tissue engineering (TE) is often limited to the outside region resulting in a localized, non-uniform tissue formation. For the present study, Cryo-Save provided cryopreserved stem cells that show promising results to obtain a uniform cell distribution and a high cell density in the centre of bone grafts. This will improve bone deficit treatments for large size bone grafts.

Cryo-Save, Europes leading family stem cell bank, participated in a high-level tissue engineering study, headed by Dr. Heidi A. Declercq, PhD and her team from Ghent University (group leader, Prof. Dr. M. Cornelissen), Belgium, on new practices to build artificial bone tissue with stem cells. Close collaboration between Cryo-Save and Ghent University led the company to manufacture and provide cryopreserved stem cells derived from adipose tissue (ADSC) for the study. The article "Bone grafts engineered from human adipose-derived stem cells in dynamic 3D-environments" was recently published in Biomaterials, one of the most widely read and influential scientific journal in the field of Tissue Engineering and Biomaterials.

Thanks to the work of Dr. Declercq, modular tissue engineering offers an innovative way to create large bone grafts obtained with ADSC-seeded on microcarriers in a bottom-up approach. The strategy aims to engineer small volume, high-quality microtissues and the subsequent assembly in-vitro or in-vivo into larger tissue constructs upon implantation. In this study, ADSC-seeded microcarriers were exploited to prepare modular tissues (microtissues) as building blocks followed by self-assembling into macrotissues in-vitro. As a result, Dr. Declercq demonstrated that ADSC are as good as bone marrow in bone tissue engineering application revealing similar morphology, calcification level and osteogenic genes expression but the use of ADSC can substitute the painful collection of bone marrow stem cells.

The outcomes of the study are very promising for treatment of bone deficits. Dr. Declercq sees great hopes in bone tissue engineering and says: "Modular tissue engineering is a promising approach to create large bone grafts as it encounters most of the limits in traditional tissue engineering. Moreover, the combination of adipose-derived stem cells in this bottom-up approach is excellent because adipose-derived stem cells are a great source for tissue engineering purposes. A high amount of cells with high proliferation and differentiation capacity can be obtained from abundant adipose tissue sources".

Cryo-Save is thrilled to have played a major role by providing cryopreserved ADSC for use in this study. It is an integral part of Cryo-Saves activities to support research and to collaborate with leading universities, physicians and stem cell scientists, with the aim to improve clinical applications.

Cryo-Save, the leading international family stem cell bank, stores more than 225,000 samples from umbilical cord blood, cord tissue and adipose tissue. There are already many diseases treatable by the use of stem cells, and the number of treatments will only increase. Driven by its international business strategy, Cryo-Save is now represented in 40 countries on three continents, with ultra-modern processing and storage facilities in Belgium, Germany, Dubai, India and South Africa.

Cryo-Save: http://www.cryo-save.com/group

Cryo-Save Group N.V.

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Bone Tissue Engineering Study Led by Ghent University Improves Treatment of Bone Deficits Using Cryo-Save Stem Cells

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