Blood Stem Cell Research and Sources

BLOOD/HEMATOPOIETIC STEM CELLS (HSC)

First identified stem cells were the blood stem cells that were discovered in the 1960s and began the stem cell research. They are also known as haematopoietic stem cells and have self-renewal property. There are two kinds of blood stem cells. One is called hematopoietic stem cells, that can give rise to virtually all types of blood cells. The second population is known asbone marrow stromal stem cellswhich can generate cartilage, fat, bone cells that support the formation fibrous connective tissue. Differentiated blood cells are short lived, so they are replaced continuously. Blood stem cells produce them. All the mature blood cells are generated from hematopoietic stem cells (HSCs) and their progenitors. Each day human body produces billions of red blood cells , white blood cells, and platelets. Loss of blood cells causes varied homeostatic mechanisms which allows production of blood cells to respond quickly to trauma and stresses like infection or bleeding. The highly organized process of homeostasis and blood cell production is coined as hematopoiesis. Each HSCs are able to produce a large number of red blood cells, a variety of lymphoid, myeloid cells like natural killer cells, B cells, T cells, macrophages, monocytes, dendritic cells and microglial cells etc and platelets over many years. Hematopoietic disorders can cause lymphoma, myelodysplasia, leukemia, aplastic anemia, inborn errors of metabolism, myeloproliferative disorders. With the help of stem cell therapy, these could become curable. Secondary source of HSCs are in other tissues including umbilical cord blood and peripheral blood. They are also found in the spleen, liver, and in many organs. And in the bone marrow of the vertebrae (backbones), thigh bones (femurs), in pelvis or hips, and the rib cage. They can be also obtained from the placenta during birth and umbilical cord blood.

CURRENT RESEARCH

Blood stem cell development is still a developing process. There are many to know about thier control in adult body and their useful role in certain blood diseases like leukaemia and anemia etc. In many blood diseases bone marrow transplant is the only possible way. Bone marrow transplant requires suitable donor to avoid graft rejection of the transplant although small risk of rejection still remains.but in case of blood stem cells obtained from umbilical cord blood there is no requirement of matching between patient and donor as umbilical cord blood stem cells are not completely developed cells but the problem of using blood stem cell is that Umbilical cord blood do not contain enough stem cells for the treatment of an adult. new investigations are continuing to produce alternatives for the production of a large number of stem cells in lab.

POTENT SOURCES OF BLOOD STEM CELLS :

Peripheral blood stem cells:

Other than the bone marrow, a small number of blood stem cells are also present in the bloodstream. They are PBSCs or peripheral blood stem cells, they can be also used like bone marrow stem cells to treat cancers, leukemia, and various blood disorders. PBSCs are easier to collect than bone marrow since they can be procure from drawn blood, not from inside of bones.This less invasive process of treatment makes peripheral blood stem cells more promisable. PBSCs are scattered in the bloodstream, however, so collecting them to perform a transplant can pose a challenge.

Umbilical cord blood stem cells:

Umbilical cord of newborn infants are discarded as a biproduct of birth process. Once collected, umbilical cord can be cryopreserved in a cord blood bank and would be available for use by the donor and compatible siblings as stem-cell–rich blood in umbilical cord has proven very useful in various treatments than PBSCs and bone marrows. These blood stem cells are less prone to graft rejection as they have not yet developed features that can be recognized by recipient’s immune system and also lacks well developed immune cells. There is always a considerable risk to develop Graft versus Host Disease when the recipient and transplanted cord blood cells are mismatched at 1 or 2 of the 6 major HLA antigen sites. Thus the reduced stringency of HLA matching required in the case of cord blood enhances the likelihood of identifying a more appropriate unit for hematopoietic stem cell transplantation. The availability; versatility and potential of umbilical cord blood stem cells make them a potent source for transplantation.

RED BLOOD CELLS FROM EMBRYONIC STEM CELLS

As Red blood cells carry oxygen throughout the body. A huge loss of blood requires blood transfusion. Red blood cells from embryonic stem cells can be developed as embryonic stem cells has the property to produce any kind of cell.so that could be the limitless souce of blood if blood stem cells can be produce from embryonic stem cells when enough blood donors are not present to meet patient needs. Salvation of The umbilical cord blood and placental blood ,procures sufficient precursor cells to support consistently to the patients weighing about 40 kg or less .blood stem cells can be transplanted to produce blood throughoutva persons life.the process of making small numbers of red blood cells is already possible from embryonic stem cells in the lab. Researchers are trying to develope blood stem cells from induced pluripotent stem (iPS) cells. As these cells could be made from patient’s own skin and can be used to produce blood stem cells. This would also defeat the problem of immune rejection. techniques for the production of large numbers of red blood cells are still to be develope.

BLOOD STEM CELL NICHE

Niches are microenvironment of local tissues that regulates and maintains stem cells.recent conclusion has been made that the niche for haematopoietic stem cell is in bone marrow.it is perivascular,created partly by endothelial cells and mesenchymal stromal cells.

A major blood vessel i.e, dorsal aorta in the mammalian embryo is the site where first haematopoietic stem cells emerge. binding with endothelial walls they produce a lifetime of blood. A protein named RUNX 1 allows haemogenic endothelial cells to produce stem cells. RUNX 1 is a regulator that promotes stem cell production . a specific sequence within the gene GATA 2 causes the elevation of GATA 2 protein which inturn elevates the level of RUNX 1 and other regulatory factors in the endothelial cells .Thus control stemcell production.

ISOLATION

Peripheral blood stem cells can be obtained by injecting a cytokine such as G-CSF that induce peripheral blood stem cells to leave from bone marrow and circulate in blood vessels.

Haematopoetic stem cells and its progenitor can be isolated by 1) negative selection and 2) positive selection

1. NEGATIVE SELECTION: is the depletion of the mature blood cells that express antigens for specific lineage.
2. POSITIVE SELECTION: is human haematopoietic stem cells isolation that express CD34 antigen specific progenitor cells.

GROWTH FACTORS

The identification and production of growth factors that stimulate maturation and proliferation of haematologic cells have create a major advancement in oncology and haematology.use of these haematopoietic growth factors has improvd the quality of life for many patients.many cytokines have identified that that influence developement of different haematologic cells.balanced secretion of these cytokines within microenvironment surrounding peripheral stem cells determines the differentiation. Growth factors like G-CSF (granulocyte colony stimulating factors), GM-CSF (granulocyte macrophage colony stimulating factors), Erytropoeitin play an important role in differentiation and proliferation of haematopoietic stem cells. G-CSF mainly acts on neutrophils.it acts by a variety of mechanisms.it differentiate progenitor cells toward neutrophil lineage and stimulate neutrophil maturation. It also increases the number of neutrophil so that it could fight against bacteria.G-CSF also stimulate granulocyte colonies. Granulocyte macrophage colony stimulating factors stimulates colonies containing monocytes, eosinophils and neutrophils by increasing their number and improving their functions.another growth factor i.e, erythropoietin stimulates stem cells toward the production of Red blood cells.although its result is usually seen after 7 days from application. It can be administered subcutaneously,intramuscularly And intravenously, iron is necessary for erythropoietin to work. Thrombopoeitin also prevent depletion of platelets .Application of these growth factors can improve the production of three major groups of blood cells i.e, red blood cells, white blood cells and platelets.

TRANSPLANTATION

Haematopoeitic stem cell transplantation involves intravenous infusion of allogeneic or autologous stem cells to reestablish hematopoietic functions in those patientswho has defective immune system and damaged bone marrow.

CONDITIONS FOR SUCCESSFUL ADULT STEM CELLS TREATMENTS REQUIRES

1. Reproduction of blood stem cells in large quantities are needed to provide the amount for treatments.
2. Production of cell types that are needed by the body.
3. Precautions to avoid rejection.
4. To Stay alive and functional for the rest of life.

USE OF CORD BLOOD STEM CELLS IN THE FOLLOWING REGENERATIVE MEDICINE APPLICATIONS:

Type 1 diabetes

Autologous cord blood stem cells applied to children with Type 1 diabetes will affect metabolic control than standard insulin treatments. cord blood stem cell infusion is safe and may come up with some slowing of the reduction of insulin production in children affected with type 1 diabetes.

Cardiovascular

Blood stem cells from umbilical cord have a great future in cardiovascular repair. In myocardial infarction of animal model,they have shown the ability to migrate selectively to damaged cardiac tissue to improve blood flow and vascular function at the site of injury, thus improve overall heart function.

Central nervous system

Cord blood stem cells when injected intravenously in animal model have shown the capability to migrate to the location of brain injury.when human cord blood stem cells were administrated into animal models with stroke ,improvement was seen as it stimulated the formation of new neurons and blood vessels in the brain. children with cerebral palsy and other kinds of brain injury when administered with cord blood infusions of their own facilitates repair of injured brain tissue, including cerebral palsy reported good progress .

As clinical studies exibit, probably cord blood stem cells will be an main resource as medicine proceeding towards exploiting the body’s own cells for treatment. The field of regenerative medicine can be predicted to benefit markedly as additional cord blood stem cell implimentations are researched and more people can have access to their own conserved cord blood.