Bone Marrow Transplants

1. Introdction

Bone marrow transplantation (BMT) is a relatively simple medical procedure being used to treat diseases once thought incurable. Since its first successful use in 1968, BMT's have been used to treat patients diagnosed with leukemia, aplastic anemia, lymphomas such as Hodgkin's disease, multiple myeloma, immune deficiency disorders and some solid tumors such as breast and ovarian cancer. At Beike we have been using BMT's for over one year for diagnosis such as Muscular dystrophy, Multiple sclerosis, ALS and Spinal cord injuries as well as some Ataxia cases and other neurological disorders. We find them very effective it boasting the potential of our umbilical cord stem cells. In addition they also "kick in" later than the typical stem cells we use which seems to allow patients with progressive disorders to have longer periods of stability.

In April of 2008 we installed a brand new operating suite and processing lab at our Hang Zhou facility in an effort to make this option available to more of our clients. This now allows patients to receive their BMT's at one of our top locations in a controlled environment where Beike can oversee every step and ensure the highest quality of cells. We brought in one of China's premier authorities on bone marrow transplants and processing to consult on our new lab, with our scientists and to work along side our medical team. In addition we have relocated one of our very best doctors from our location in Shenyang who has a wealth of experience in performing bone marrow collection to oversee the procedures and provide instruction for our local team in Hangzhou.

*In November of 2008 our newest bone marrow lab at our Qingdao location opens. This will allow even more of our clients to partake in the option of a BMT. Qingdao is one of the largest stem cell treatment facilities in the world and can take over 30 patients per month. Again we have brought in a team of experts to facilitate the opening of the lab and training of the staff to ensure the continuity of care and service.

FACT: We use the patients own bone marrow and thus "matching is not an issue and immunosuppressant drugs and chemotherapy are not required.

For those undergoing this procedure they will have one bone marrow aspiration procedure, which is detailed out below, followed by one spinal reinfusion of their cells which we have processed using our own special technique. Once the marrow has been extracted it goes through two separate cultures. One culture yields Neural Stem Cells (NSC). The process of culturing and expanding these bone marrow derived cells is much the same as it is with our umbilical stem cells in that we infuse Neural Growth Factors into the growth medium to enhance their ability to target and differentiate into neural cells (white matter). It takes approximately 2 to 3 days for this cell type to reach full maturity and once these cells reach full maturity they are cleansed to be free of all growth medium. The second culture requires 7 to 10 days to reach maturity as it is designed to expand and multiply the number of Mesenchymal Stem Cells (MSC) found in the bone marrow. MSC's are one of the rarest stem cell subsets found in cord blood but they are plentiful in the bone marrow and extremely effective when given in high dosages (numbers). For this reason we do the separate culture just to target and increase the numbers of Mesenchymal cells. Once these cells reach full maturity they are also cleansed to be free of all growth medium and then the cells from both culturings are prepared together and injected into the client's body via a spinal injection. The number of cells yielded at the end of the process depends somewhat on the amount of marrow which can be extracted from the patient during the surgical procedure but typically the total number of stem cells reintroduced into the client is between 1 and 1.5 Billion. The average ratio of NSC to MSC is 1:1 or about half Mesenchymals and half Neural Stem Cells. It should be noted that this processing method is unique to Beike Biotech.

Criteria for bone marrow obtained stem cell samples

FACT: In the Untied States1991, more than 7,500 people underwent BMT's nationwide.

2. What is Bone Marrow?

Bone marrow is a spongy tissue found inside bones. The bone marrow in the breast bone, skull, hips, ribs and spine contains stem cells that produce the body's blood cells. These blood cells include white blood cells (leukocytes), which fight infection; red blood cells (erythrocytes), which carry oxygen to the body and remove waste products from organs and tissues; and platelets, which enable the blood to clot. Generally we obtain the marrow from the upper crest of the pelvic bone.

FACT: When using the patients own bone marrow it is called an autologous BMT.

3. Why Transplant?

While bone marrow transplants do not provide 100 percent assurance that the disease will not recur, a transplant can prolong the period of disease-free survival for manypatients with progressive disorders. We have also noted their apparent ability to boast the effects of our typical umbilical cord stem cells. In addition, the processing yields two different cell types, MNC and EPC which affect the body in ways the umbilical cord stem cells do not, often resulting in improvements in other areas of the body. This allows the patient to experience changes in areas that they might not otherwise see.

FACT: Bone marrow contains Mesenchymal stem cells (also called marrow stromal cells). These cells are multipotent cells that can differentiate into a variety of cell types. Cell types that MSCs have been shown to differentiate into osteoblasts, chondrocytes, adipocytes and beta-pancreatic islets cells. They can also transdifferentiate into neuronal cells. Source; Wikipedia encyclopedia

4. Preparing for the Transplant

A successful transplant requires the patient be healthy enough to undergo the transplant procedure. Age, general physical condition, the patient's diagnosis and the stage of the disease are all considered by the physician on site when determining whether a person should undergo a transplant. Your medical consultant can assist you with pre-screening to determine if you are a possible candent for this surgery but the final decision is always left to the treating doctor on site.

Prior to a bone marrow transplant, a battery of tests are carried out during the patient's initial evaluation upon entering the hospital to ensure the patient is physically capable of undergoing a transplant. X-rays and blood tests are done to determine kidney function, immune system status and other vital organ functions all of which are used to develop a patient profile. The pre-transplant tests are usually done within the first 2 to 3 days of admission.

A successful bone marrow transplant requires an expert medical team - doctors, nurses, and other support staff - who are experienced in bone marrow transplants. Beike teams are trained to promptly recognize problems and emerging side effects, and know how to react swiftly and properly if problems do arise. Our bone marrow transplant program also recognizes the importance of providing patients and their families with emotional and psychological support before, during and after the transplant.

Contraindications for Bone Marrow Harvesting

These are items that may indicate that the patient would not be a suitable for a bone marrow aspiration procedure.

• Decreased lung and/or oxygenating capacity
• Severe anemia
• Osteoporosis of the hip bones and/or pelvic girdle
• The use of supplemental oxygen
• Under the age of six
• Over the age of sixty five
• Severe scoliosis which may affect the lung capacity
   

5. Bone Marrow Harvest

The bone marrow harvest takes place in our specially designed hospital operating room, under twilight sedation which employs the use of IV Valium and using local anesthesia at the insertion site. It involves little risk and minimal discomfort.

While the patient is under anesthesia, a needle is inserted into the cavity of the rear hip bone or "iliac crest" where a large quantity of bone marrow is located. The bone marrow a thick, red liquid - is extracted with a needle and syringe. More than one insertion into the on the hip may be required to extract the requisite amount of bone marrow. There are no surgical incisions or stitches involved - only skin punctures where the needle was inserted.

The amount of bone marrow harvested depends on the size of the patient and the concentration of bone marrow cells. Usually less than one quart of marrow is harvested; while this may sound like a lot, it really only represents about 0.5 to 1% of a person's bone marrow, which the body replaces in two to four weeks.

When the sedation wears off, the patient may feel some discomfort at the harvest site. The pain will be similar to that associated with a fall onto the hip and can usually be controlled with Tylenol and Ibuprofen. Bring these items with you and feel free to use them before and after the procedure. Patient will need to be on bed rest for a few hours post the collection procedure. The first two days after the collection the patient will be on light activities and will need to stay in the hospital after which they can resume normal activities including participation in the rehabilitation program.

*Aside from fatigue, minor discomfort, mild pain and stiffness the other risks although uncommon include minor blood loss and infection at the insertion site.

FACT: Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas whose work was later recognized with a Nobel Prize in Physiology and Medicine.

6. Bone Marrow Aspiration

A small amount of bone marrow is removed during a bone marrow aspiration. The procedure is uncomfortable, but can be tolerated by both children and adults.

7. Handling Emotional Stress

In addition to the physical discomfort associated with the transplant experience there is emotional and psychological discomfort as well. Some patients find the emotional and psychological stress more problematic than the physical discomfort. The psychological and emotional stress stems from several factors. First, patients undergoing transplants are already traumatized by the news that they have a life-threatening disease or injury. While the transplant offers hope for their recovery, the prospect of undergoing a medical procedure is still not pleasant and there's no guarantee of success. Patients have also traveled a long way to receive their transplants and the stress of such a journey should not be underestimated.

Helplessness and fear are common feelings among transplant patients. For many, it's unnerving to be totally dependent on strangers for your care, no matter how competent they may be. The fact that patients are unfamiliar with the language and environment compounds these feelings and increases their stress. Some also find it embarrassing to be dependent on strangers for help with basic daily functions such as using the washroom. These issues should all be taken into consideration when you, the patient, are choosing your traveling companion. We also strongly urge clients to ask for assistance when ever they need it from our medical team and/or our translation and coordination team members. Do not forget that your medical consultant, while not on site, can still be of help and support to you during this time. They can be reached by email and/or by phone.

8. Abstracts of Interest

Uncovering How Bone Marrow Cells Can Potentially Regenerate Brain Tissue

Japanese researchers have found a piece of the "missing link" about how bone marrow cells restore lost neurologic function when transplanted into animals exhibiting central nervous system disorders, according to a study in the March issue of the Journal of Nuclear Medicine.

"Our study showed that cell transplantation therapy may improve brain receptor function in patients who suffered from cerebral stroke, improving their neurological symptoms," said Satoshi Kuroda, M.D., Ph.D., who is with the department of neurosurgery at Hokkaido University School of Medicine in Sapporo, Japan.

What researchers do know is that cells found in bone marrow may provide a safe, ethical source for replacing brain cells lost to neurological disorders such as Alzheimer's and Parkinson's diseases. Studies have shown that cells taken from human bone marrow may possibly be converted into neural cells.

Using autoradiography (a technique that uses X-ray film to visualize radioactively labeled molecules) and fluorescence immunohistochemistry (the testing of sections of tissue for specific proteins by attaching them with specific antibodies), the researchers examined the binding of a radioactive molecule with a specific receptor protein in animals with cerebral infarcts or strokes. Their findings "clearly showed" that bone marrow cells "may contribute to neural tissue regeneration by migrating toward the periinfarct area and acquiring the neuron-specific receptor function," reports the JNM article.

To see the full version of this Article look in Radiology/Nuclear Medicine News
Article Date: 19 Mar 2006

Techniques Push Stem Cells to Repair Damaged Nerves

New studies suggest that use of cells derived from bone marrow may prompt stem cells to repair nerve damage caused by stroke or spinal cord injury. Researchers at the Medical College of Georgia, Augusta, examined bone marrow-derived multi-potent progenitor cells, which have the ability to develop into different kinds of cells, including nervous system cells. Both human and rat bone marrow cells were transplanted into rats with induced strokes. Both types of cell transplants led to a reduction in motor impairments in the rats, the researchers reported. In neonatal rats, the transplanted cells migrated out from the transplant sites toward another nearby brain region. The Georgia team found no evidence of tumor formation. To view the entire article go to Health Day News dated April 7th 2006.

Researchers Have Evidence Bone Marrow Stem Cells Become Brain Cells

Using a potion of growth factors and other nutrients, scientists at Jefferson Medical College have shown in the laboratory they are able to convert human bone marrow stem cells into adult brain cells.

The results suggest such stem cells may have potential use in treating neurodegenerative diseases such as Parkinson's.

"The goal [of the work] is to find stem cells that we can differentiate into dopamine neurons to replace those lost in Parkinson's disease," says developmental biologist Lorraine Iacovitti, Ph.D., professor of neurology at Jefferson Medical College.

Human bone marrow stem cells - also known as pluripotent stem cells - normally give rise to human bone, muscle, cartilage and fat cells.

Other scientists have shown previously that at least a portion of mouse bone marrow stem cells treated with various growth factors and other agents will go on to resemble neurons in cell culture.

Dr. Iacovitti's team used the previous group's cocktail of growth factors and nutrients on human bone marrow stem cells and found that some cells converted to neurons."

By experimenting with different combinations of growth factors and nutrients, they eventually found a cocktail of reagents that converted 100 percent of cells within an hour - a stunning development that had never been shown before.

"It flew in the face of everything I knew from developmental biology," Dr. Iacovitti says. "We've identified factors that get 100 percent of human bone marrow stem cells converted to neurons very quickly." Not only do the converted cells look like neurons, she says, they contain neuronal proteins.

The converted stem cells have neuronal markers and markers that are identified with subclasses of neurons. "That's important because we've shown they can convert to specific classes of neurons".

"The major advantage of using adult human bone marrow stem cells is that each person can be his own donor, meaning they can have an autologous graft of cells without rejection," Dr. Iacovitti says.

Reported November 2007 at the annual meeting of the Society for Neuroscience in San Diego.

Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications

Bone marrow cells are progenitors of skeletal tissue components such as bone, cartilage and adipocytes. In addition, they may be induced to undergo unorthodox differentiation, forming neural and myogenic cells. As such, they represent an important paradigm of post-natal nonhematopoietic stem cells, and an easy source for potential therapeutic use.

Bone marrow has traditionally been seen as an organ composed of two main systems rooted in distinct lineages—the hematopoietic tissue proper and the associated supporting stroma. The evidence pointing to a putative stem cell upstream of the diverse lineages and cell phenotypes comprising the bone marrow stromal system has made marrow the only known organ in which two separate and distinct stem cells and dependent tissue systems not only coexist, but functionally cooperate. Originally examined because of their critical role in the formation of the hematopoietic microenvironment (HME), marrow cells later came to center stage with the recognition that they are the stem/progenitor cells of skeletal tissues. More recent data pointing to the unexpected differentiation potential of marrow cells into neural tissue or muscle grant them membership in the diverse family of putative somatic stem cells. These cells exist in a number of post-natal tissues that display transgermal plasticity; that is, the ability to differentiate into cell types phenotypically unrelated to the cells in their tissue of origin.

The increasing recognition of the properties of marrow cells has spawned a major switch in our perception of their nature, and ramifications of their potential therapeutic application have been envisioned and implemented. Yet, several aspects of marrow stromal cell biology remain in question and unsettled throughout this evolution both in general perspective and in detail, and have gained further appeal and interest along the way. These include the identity, nature, developmental origin and in vivo function of marrow stromal cells, and their amenability to ex vivo manipulation and in vivo use for therapy. Just as with other current members of the growing list of somatic stemcells, imagination is required to put a finger on the seemingly unlikely properties of marrow stromal cells, many of which directly confront established dogmas or premature inferences made from other more extensively studied stem cell systems. Source Stem Cells, Vol. 19, No. 3, 180-192, May 2001.

9. Suggested Reading

Popular Bone Marrow Stem Cells in Specialties Medicine Books Products

Updated by Kirshner Ross-Vaden 3/30/08

Written and copyrighted by Kirshner Ross-Vaden RN 3/30/08 for the sole use of Beike Bio-Tech and Stem Cells China. Reproduced here with permission.

All Beike health-related material is provided for information purposes only.