Bay Biosciences provides high-quality cryopreserved bone marrow aspirate samples, with matched fresh frozen sera (serum), plasma, and peripheral blood mononuclear cells (PBMC) bio-fluids, from patients diagnosed with chronic lymphocytic leukemia (CLL).
The bone marrow aspirate, sera (serum), plasma and peripheral blood mononuclear cells (PBMC) biofluid specimens are processed from chronic lymphocytic leukemia (CLL) patients peripheral whole-blood using customized collection and processing protocols.
Fresh frozen tissue and matched biofluid samples were, collected from unique patients diagnosed with chronic lymphocytic leukemia (CLL).
Bio-samples are provided to a valued pharmaceutical customer for research, diagnostics, discovery, and drug development.
Bone Marrow Overview
Bone marrow is the spongy tissue inside some of the bones in the body, including the hip and thigh bones. It contains immature cells called stem cells.
Most patients with blood cancers, such as leukemia and lymphomas, sickle cell anemia, and other life threatening conditions rely on bone marrow or cord blood transplants to survive.
People need healthy bone marrow and blood cells to live. When a condition or disease affects bone marrow so that it can no longer function effectively, a marrow or cord blood transplant could be the best treatment option. For certain patients, it may be the only option.
What is Bone Marrow?
Bone marrow is soft, gelatinous tissue that fills the medullary cavities, or the centers of bones. There are two types of bone marrow are red bone marrow, known as myeloid tissue, and yellow bone marrow, known as fatty tissue.
Both types of bone marrow are enriched with blood vessels and capillaries.
Bone marrow makes more than 220 billion new blood cells every day. Most blood cells in the body develop from cells in the bone marrow.
Bone Marrow Stem Cells
Bone marrow contains two types of stem cells: mesenchymal and hematopoietic.
Red bone marrow consists of a delicate, highly vascular fibrous tissue containing hematopoietic stem cells. These are blood-forming stem cells.
Yellow bone marrow contains mesenchymal stem cells, or marrow stromal cells. These produce fat, cartilage, and bone.
Stem cells are immature cells that can turn into a number of different types of cells.
Hematopoietic stem cells in the bone marrow give rise to two main types of cells: myeloid and lymphoid lineages. These include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells, and megakaryocytes, or platelets, as well as T cells, B cells, and natural killer (NK) cells.
The different types of hematopoietic stem cells vary in their regenerative capacity and potency. They can be multipotent, oligopotent, or unipotent, depending on how many types of cells they can create.
Pluripotent hematopoietic stem cells have renewal and differentiation properties. They can reproduce another cell identical to themselves, and they can generate one or more subsets of more mature cells.
The process of developing different blood cells from these pluripotent stem cells is known as hematopoiesis. It is these stem cells that are needed in bone marrow transplants.
Stem cells constantly divide and produce new cells. Some new cells remain as stem cells, while others go through a series of maturing stages, as precursor or blast cells, before becoming formed, or mature, blood cells. Stem cells rapidly multiply to make millions of blood cells each day.
Blood cells have a limited life span. This is around 120 days for red blood cells. The body is constantly replacing them. The production of healthy stem cells is vital.
The blood vessels act as a barrier to prevent immature blood cells from leaving bone marrow.
Only mature blood cells contain the membrane proteins required to attach to and pass through the blood vessel endothelium. Hematopoietic stem cells can cross the bone marrow barrier, however. Healthcare professionals may harvest these from peripheral, or circulating, blood.
The blood-forming stem cells in red bone marrow can multiply and mature into three significant types of blood cells, each with its own job:
- Red blood cells (erythrocytes): These transport oxygen around the body.
- White blood cells (leukocytes): These help fight infection and disease. White blood cells include lymphocytes, which make up the cornerstone of the immune system, and myeloid cells, which include granulocytes, neutrophils, monocytes, eosinophils, and basophils.
- Platelets (thrombocytes): These help with blood clotting after injury. Platelets are fragments of the cytoplasm of megakaryocytes, which are another type of bone marrow cell.
Once mature, these blood cells move from bone marrow into the bloodstream, where they perform important functions that keep the body alive and healthy.
Mesenchymal stem cells are present in the bone marrow cavity. They can differentiate into a number of stromal lineages, such as:
- Adipocytes (adipose tissue)
- Chondrocytes (cartilage generation)
- Endothelial cells
- Fibroblasts
- Osteoclasts
- Myocytes (muscle)
- Macrophages
- Osteoblasts (bone formation)
Red Bone Marrow
Red bone marrow produces all red blood cells and platelets and around 60–70% of lymphocytes in human adults. Other lymphocytes begin life in red bone marrow and become fully formed in the lymphatic tissues, including the thymus, spleen, and lymph nodes.
Together with the liver and spleen, red bone marrow also plays a role in getting rid of old red blood cells.
Yellow Bone Marrow
Yellow bone marrow mainly acts as a store for fats. It helps provide sustenance and maintain the correct environment for the bone to function. However, under particular conditions, such as with severe blood loss or during a fever, yellow bone marrow may revert to red bone marrow.
Yellow bone marrow tends to be located in the central cavities of long bones and is generally surrounded by a layer of red bone marrow with long trabeculae (beam-like structures) within a sponge-like reticular framework.
Bone Marrow Timeline
Before birth but toward the end of fetal development, bone marrow first develops in the clavicle. It becomes active about 3 weeks later. Bone marrow takes over from the liver as the major hematopoietic organ at 32–36 weeks’ gestation.
Bone marrow remains red until around the age of 7 years, as the need for new continuous blood formation is high. As the body ages, it gradually replaces the red bone marrow with yellow fat tissue. Adults have an average of about 2.6 kilograms (kg) (5.7 pounds) of bone marrow, about half of which is red.
In adults, the highest concentration of red bone marrow is in the bones of the vertebrae, hips (ilium), breastbone (sternum), ribs, and skull, as well as at the metaphyseal and epiphyseal ends of the long bones of the arm (humerus) and leg (femur and tibia).
All other cancellous, or spongy, bones and central cavities of the long bones are filled with yellow bone marrow.
Function of Bone Marrow
Most red blood cells, platelets, and most white blood cells form in the red bone marrow. Yellow bone marrow produces fat, cartilage, and bone.
White blood cells survive from a few hours to a few days, platelets for about 10 days, and red blood cells for about 120 days. Bone marrow needs to replace these cells constantly, as each blood cell has a set life expectancy.
Certain conditions may trigger additional production of blood cells. This may happen when the oxygen content of body tissues is low, if there is loss of blood or anemia, or if the number of red blood cells decreases. If these things happen, the kidneys produce and release erythropoietin, which is a hormone that stimulates bone marrow to produce more red blood cells.
Bone marrow also produces and releases more white blood cells in response to infections and more platelets in response to bleeding. If a person experiences serious blood loss, yellow bone marrow can activate and transform into red bone marrow.
Healthy bone marrow is important for a range of systems and activities.
Circulatory system
The circulatory system touches every organ and system in the body. It involves a number of different cells with a variety of functions. Red blood cells transport oxygen to cells and tissues, platelets travel in the blood to help clotting after injury, and white blood cells travel to sites of infection or injury.
Hemoglobin
Hemoglobin is the protein in red blood cells that gives them their color. It collects oxygen in the lungs, transports it in the red blood cells, and releases oxygen to tissues such as the heart, muscles, and brain. Hemoglobin also removes carbon dioxide (CO2), which is a waste product of respiration, and sends it back to the lungs for exhalation.
Iron
Iron is an important nutrient for human physiology. It combines with protein to make the hemoglobin in red blood cells and is essential for producing red blood cells (erythropoiesis). The body stores iron in the liver, spleen, and bone marrow. Most of the iron a person needs each day for making hemoglobin comes from the recycling of old red blood cells.
Red Blood Cells
The production of red blood cells is called erythropoiesis. It takes about 7 days for a committed stem cell to mature into a fully functional red blood cell. As red blood cells age, they become less active and more fragile.
White blood cells called macrophages remove aging red cells in a process known as phagocytosis. The contents of these cells are released into the blood. The iron released in this process travels either to bone marrow for the production of new red blood cells or to the liver or other tissues for storage.
Typically, the body replaces around 1% of its total red blood cell count every day. In a healthy person, this means that the body produces around 200 billion red blood cells each day.
White Blood Cells
Bone marrow produces many types of white blood cells. These are necessary for a healthy immune system. They prevent and fight infections.
The main types of white blood cells, or leukocytes, are as follows.
Lymphocytes
Lymphocytes are produced in bone marrow. They make natural antibodies to fight infection due to viruses that enter the body through the nose, mouth, or another mucous membrane or through cuts and grazes. Specific cells recognize the presence of invaders (antigens) that enter the body and send a signal to other cells to attack them.
The number of lymphocytes increases in response to these invasions. There are two major types of lymphocytes: B and T lymphocytes.
Monocytes
Monocytes are produced in bone marrow. Mature monocytes have a life expectancy in the blood of only 3–8 hours, but when they move into the tissues, they mature into larger cells called macrophages.
Macrophages can survive in the tissues for long periods of time, where they engulf and destroy bacteria, some fungi, dead cells, and other material that is foreign to the body.
Granulocytes
“Granulocytes” is the collective name given to three types of white blood cells: neutrophils, eosinophils, and basophils. The development of a granulocyte may take 2 weeks, but this time reduces when there is an increased threat, such as a bacterial infection.
Bone marrow stores a large reserve of mature granulocytes. For every granulocyte circulating in the blood, there may be 50–100 cells waiting in the bone marrow to be released into the bloodstream. As a result, half the granulocytes in the bloodstream can be available to actively fight an infection in the body within 7 hours of it detecting one.
Once a granulocyte has left the blood, it does not usually return. A granulocyte may survive in the tissues for up to 4–5 days, depending on the conditions, but it can only survive for a few hours in circulating blood.
Neutrophils
Neutrophils are the most common type of granulocyte. They can attack and destroy bacteria and viruses.
Eosinophils
Eosinophils are involved in the fight against many types of parasitic infections and against the larvae of parasitic worms and other organisms. They are also involved in some allergic reactions.
Basophils
Basophils are the least common of the white blood cells. They respond to various allergens that cause the release of histamines, heparin, and other substances.
Heparin is an anticoagulant. It prevents blood from clotting. Histamines are vasodilators that cause irritation and inflammation. Releasing these substances makes a pathogen more permeable and allows for white blood cells and proteins to enter the tissues to engage the pathogen.
The irritation and inflammation in tissues that allergens affect are parts of the reaction associated with hay fever, some forms of asthma, hives, and, in its most serious form, anaphylactic shock.
Platelets
Bone marrow produces platelets in a process known as thrombopoiesis. Platelets are necessary for blood to coagulate and for clots to form in order to stop bleeding.
Sudden blood loss triggers platelet activity at the site of an injury or wound. Here, the platelets clump together and combine with other substances to form fibrin. Fibrin has a thread-like structure and forms an external scab or clot.
Platelet deficiency causes the body to bruise and bleed more easily. Blood may not clot well at an open wound, and there may be a higher risk of internal bleeding if the platelet count is very low.
Lymphatic System
The lymphatic system consists of lymphatic organs such as bone marrow, the tonsils, the thymus, the spleen, and lymph nodes.
All lymphocytes develop in bone marrow from immature cells called stem cells. Lymphocytes that mature in the thymus gland (behind the breastbone) are called T cells. Those that mature in bone marrow or the lymphatic organs are called B cells.
Immune System
The immune system protects the body from disease. It kills unwanted microorganisms such as bacteria and viruses that may invade the body.
How does the immune system fight infection?
Small glands called lymph nodes are located throughout the body. Once lymphocytes are made in bone marrow, they travel to the lymph nodes. The lymphocytes can then travel between each node through lymphatic channels that meet at large drainage ducts that empty into a blood vessel.
Lymphocytes enter the blood through these ducts. Three major types of lymphocytes play an important part in the immune system immune system: B lymphocytes, T lymphocytes, and NK cells.
B-Lymphocytes (B Cells)
These cells originate from hematopoietic stem cells in bone marrow in mammals.
B cells express B cell receptors on their surface. These allow the cell to attach to an antigen on the surface of an invading microbe or another antigenic agent.
For this reason, B cells are known as antigen-presenting cells, as they alert other cells of the immune system to the presence of an invading microbe.
B cells also secrete antibodies that attach to the surface of infection-causing microbes. These antibodies are Y-shaped, and each one is akin to a specialized “lock” into which a matching antigen “key” fits. Because of this, each Y-shaped antibody reacts to a different microbe, triggering a larger immune system response to fight infection.
In some circumstances, B cells erroneously identify healthy cells as being antigens that require an immune system response. This is the mechanism behind the development of autoimmune conditions such as multiple sclerosis, scleroderma, and type-1 diabetes.
T-Lymphocytes (T Cells)
These cells are so-called because they mature in the thymus, which is a small organ in the upper chest, just behind the sternum. (Some T cells mature in the tonsils.)
There are many different types of T cells, and they perform a range of functions as part of adaptive cell-mediated immunity. T cells help B cells make antibodies against invading bacteria, viruses, or other microbes.
Unlike B cells, some T cells engulf and destroy pathogens directly after binding to the antigen on the surface of the microbe.
NK T cells, not to be confused with NK cells of the innate immune system, bridge the adaptive and innate immune systems. NK T cells recognize antigens presented in a different way from many other antigens, and they can perform the functions of T helper cells and cytotoxic T cells. They can also recognize and eliminate some tumor cells.
NK Cells
These are a type of lymphocyte that directly attack cells that a virus has infected.
Bone Marrow Biopsy
A bone marrow biopsy is a medical test in which a doctor requests the collection and examination of a sample of bone marrow. This is done to check if the tissue is healthy and blood cell production is normal.
In the procedure, a healthcare provider inserts a small needle into a large bone, drawing a sample of the bone marrow into the needle. Then, a laboratory technician analyzes the sample for a range of diseases, including several cancers.
Reasons for Bone Marrow Biopsy
Doctors order bone marrow biopsies when signs or symptoms indicate problems with blood cell production.
Bone marrow biopsies are also used in people with blood-related cancers to monitor their treatment, for example, the progress of chemotherapy.
A bone marrow biopsy can support the diagnosis or evaluation of many symptoms and medical conditions.
Some of these diseases and conditions include the following:
- Anemia or a shortage of red blood cells
- Abnormal bleeding or clotting
- Bone marrow and blood cancers, such as leukemia, lymphoma, or multiple myeloma (MM)
- Cancers that have spread to the bone marrow from elsewhere
- Unexplained fever
Bone Marrow Biopsy Procedure
A bone marrow biopsy procedure takes place a doctor’s office, hospital, or clinic. A person is likely to be at the appointment for around 30 to 45 minutes in total, with the biopsy itself taking around 10 minutes.
Before the bone marrow biopsy, a doctor or other healthcare provider will ask questions to ensure the safest care. Patients may wish to prepare a list of questions and their medical history to speed up the process.
Bone marrow biopsies carry a risk of bleeding. The medical professional will ask about medications or herbal treatments a patient might be taking that could increase this risk, including common pain relievers, such as aspirin, ibuprofen, and naproxen. Anticoagulants or blood thinners may also lead to excessive bleeding.
The doctor or healthcare provider will advise on whether to continue taking medications or stop the course before the procedure.
Allergies are also an important concern when having a biopsy. The healthcare provider will ask about any allergies someone may have, especially to anesthetics and latex.
A doctor may use an anesthetic during the procedure to numb the pain. Patients receiving anesthesia may need a friend or family member to drive them home afterward.
During the Biopsy Procedure
A bone marrow biopsy typically involves two steps:
- Aspiration: The healthcare provider removes fluid from the bone marrow.
- Biopsy: The doctor removes a tiny piece of bone and bone marrow tissue.
A bone marrow biopsy usually takes place on an outpatient basis. However, some patients may have the procedure done while staying in a hospital.
The pelvic bone is the most common site for a marrow biopsy, but a doctor might use other bones.
The steps of a bone marrow biopsy are usually as follows:
Before the biopsy, the patient under examination changes into a gown. The doctor will ask them to lie on their side or stomach. The position may vary according to the site of the biopsy. The medical professional then cleans the biopsy area with an antiseptic.
The doctor applies an anesthetic with a needle to numb the biopsy area. Some pain might occur when the needle penetrates the skin, and the anesthetic enters the area.
Once the biopsy site is numb, the healthcare provider makes a small incision at the biopsy site. Bone marrow aspiration usually takes place first. The medical professional will use a syringe to take a liquid sample of the bone marrow cells.
After the aspiration comes the bone marrow biopsy. A biopsy needle is larger than an aspiration needle. The doctor guides the needle into the bone, rotates it, and removes a sample of bone and tissue.
After the Biopsy Procedure
The results may be ready a few days after the biopsy but might take longer. A pathologist or hematologist, or doctor specializing in blood, will analyze the samples.
Your doctor will then explain the results and possibly arrange follow-up tests.
The biopsy area may be sore for several days. It is important to closely follow the treating doctor instructions about which pain relievers are safe to use. Some pain relievers, including aspirin, can increase the risk of bleeding after a bone marrow biopsy.
Your doctor will give instructions about keeping the area dry and when the protective bandage may come off. The bandage usually stays on for 1 to 2 days.
Watch out for physical signs that might signal an infection or complication. Patients should talk to their doctor if they experience any of the following:
Risks of a Biopsy Procedure
Bone marrow biopsies are usually safe, but the procedure carries a risk of complications. Some of the more common problems can include:
- Bruising and pain at the biopsy site
- Prolonged bleeding from the biopsy site
- Infection at or near the biopsy site
If a person has other health problems while having a bone marrow biopsy, this might also increase the risk of complications.
Bay Biosciences is a global leader in providing researchers with high quality, clinical grade, fully characterized human tissue samples, bio-specimens, and human bio-fluid collections.
Samples available include cancer (tumor) tissue, cancer serum, cancer plasma, cancer, peripheral blood mononuclear cells (PBMC). and human tissue samples from most other therapeutic areas and diseases.
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Our biobank procures and stores fully consented, deidentified and institutional review boards (IRB) approved human tissue samples and matched controls.
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This critical patient’s clinical data includes information relating to their past and current disease, treatment history, lifestyle choices, biomarkers, and genetic information.
Patient’s data is extremely valuable for researchers and is used to help identify new effective treatments (drug discovery & development) in oncology, and other therapeutic areas and diseases.
Bay Biosciences banks wide variety of human tissue samples and biological samples, including cryogenically preserved at – 80°C.
Including fresh frozen tissue samples, tumor tissue samples, formalin-fixed paraffin-embedded (FFPE), tissue slides, with matching human bio-fluids, whole blood and blood-derived products such as serum, plasma and PBMC.
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