accessible organs that contain osteoprogenitors is the periosteum of the jaw. It contains three layers, and the innermost layer contains an abundance of bone progenitor cells. These progenitor cells are isolated through maxillofacial biopsies and the cells are separated based on the markers expressed. These cells are then expanded in vitro and differentiate to osteoblasts. These osteoblasts are used in reconstruction of the jaw. It is also an effective tool for use in facial reconstruction and it eliminates the issue of immunogenicity.
Another location where the osteoprogenitor cells are present in the body from where they can be easily aspirated is the vertebral column. The vertebral column contains four layers and osteoprogenitors can be isolated from all four layers to obtain a sizable quantity. These cells are used for regenerative therapy and cell replacement purposes. Since the vertebral body is a great source, they will augment spinal fusion surgeries.
Current Technology
Osteoprogenitor cells found in the bone marrow and the periosteum are not sufficient in number for direct therapeutic purposes. The cells need to be expanded ex vivo and one of the significant disadvantages is the limited number of divisions. Several technologies have and are being developed to expand the cell ex vivo to create a panel of progenitors or osteoblasts that can be used. Companies are using an automated cell expansion system to develop these lineages. The process of automation and the need of exogenous factors will be standardized. The second phase is to test the ability of these cells to form blood vessels. Moving to the third phase from this point, the ability of these cells to heal fractures in the mouse model will be tested. Upon successful completion of the third phase, the same will be tested in phase I and II clinical trials in which the ability of these cells to heal nonunion fractures will be tested. The end product will be a therapeutic kit that aids cell replacement for healing nonunion fractures.
Sharanya Kumar
Independent Scholar
See Also: Bone: Current Research on Isolation or Production of Therapeutic Cells; Bone: Existing or Potential Regenerative Medicine Strategies.
Further Readings
Chaudhary, L. R., A. M. Hofmeister, and K. A. Hruska. “Differential Growth Factor Control of Bone Formation Through Osteoprogenitor Differentiation.” Bone, v.34/3 (2004).
Li, Z., M. Q. Hassan, S. Volinia, A. J. van Wijnen, et al. “A MicroRNA Signature for a BMP2-Induced Osteoblast Lineage Commitment Program.” Proceedings of the National Academy of Sciences, v.105/37 (2008).
McLain, R. F., C. A. Boehm, C. Rufo-Smith, and G. F. Muschler. “Transpedicular Aspiration of Osteoprogenitor Cells From the Vertebral Body: Progenitor Cell Concentrations Affected by Serial Aspiration.” Spine Journal, v.9/12 (2009).
McLain, R. F., J. E. Fleming, C. A. Boehm, and G. F. Muschler. “Aspiration of Osteoprogenitor Cells for Augmenting Spinal Fusion: Comparison of Progenitor Cell Concentrations From the Vertebral Body and Iliac Crest.” Journal of Bone and Joint Surgery, American Volume, v.87/12 (2005).
Bone Marrow Transplants
Bone Marrow Transplants
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Bone Marrow Transplants
Bone marrow is located in the interior of the bones and produces white cells for the immune system, red cells for oxygen transportation, and platelets for blood clotting. There are two types of bone marrow. Red marrow consists of mainly hematopoietic tissue, and yellow marrow consists mainly of fat cells. At birth all marrow is red, but with age, half of it is transformed into yellow marrow. Red marrow is found mainly in the flat bones such as the pelvis, sternum, and cranium, and in the ends of long bones such as the femur and humerus. Here hematopoiesis takes place, which is the formation of blood cellular components.
Surgeon Dr. Hans Janovich performs a bone marrow harvest operation. The procedure consists of inserting a large-gauge syringe into an area of the hip and extracting the bone marrow. This autologous transplantation was performed in order to recreate and replenish T-cells and the white and red blood cells killed while the patient underwent chemotherapy. (U.S. Navy/Chad McNeeley)
Approximately 1011–1012 new blood cells are produced daily in order to maintain steady-state levels in the bloodstream. All blood cells derive from hematopoietic stem cells that reside in the red bone marrow. They give rise to different precursor cells that eventually will differentiate and become mature blood cells. The bone marrow stroma is made up of other cell types such as fibroblasts and cells involved in the formation of bone structure, such as osteoblasts and osteoclasts. They are indirectly involved in hematopoiesis by secreting growth factors and cytokines, which influence the development of different cell types.
Since the 1950s there has been tremendous development of the procedure whereby bone marrow is transplanted from a healthy donor to a patient in need of restored bone marrow function, and since the 1970s it has been in clinical use. In 1990, E. Donnal Thomas and Joseph E. Murray received the Nobel Prize in Physiology or Medicine for their pioneering work on bone marrow transplantation. Today this is mainly used for patients with diseases that originated in the bone marrow, such as acute leukemia, but an increasing number of patients are treated for a wide variety of other diseases. Bone marrow transplantation is today mainly synonymous with hematopoietic stem cell transplantation (HSCT) whereby the cells are harvested by a procedure called apheresis from the peripheral blood of a healthy donor or the patient prior to treatment. Apheresis is a technique in which a person’s blood is passed from a vein through a machine that sorts out the stem cells and then the blood is given back. The cells can also be harvested as bone marrow by aspiration from the pelvic bone or from the umbilical cord of newborn infants. This is mainly used for donations to siblings with malignant or inborn diseases, but donation to unrelated children and adults is also possible.
Allogeneic Transplantation
An allogeneic transplantation is a procedure whereby stem cells are transferred from a healthy person to a patient. Candidates for this regimen are mainly patients with cancer diseases of the blood, such as acute leukemias, in which conventional cytostatics has failed or the genetic profile of the disease predicts a poor prognosis. Other conditions treated with stem cell transplants include sickle-cell disease, myelodysplastic syndrome, and aplastic anemia. Children could be treated for diseases such as severe combined immunodeficiency (SCID) or congenital neutropenia.
Thorough investigations of both the patient and the donor are carried out in order to ensure that they could manage the treatment. This includes examination of vital organ function such as heart, lungs, and kidneys but also screening for diseases that could complicate the transplantation. The donor should preferably be a sibling or an unrelated donor with a matching HLA (human leukocyte antigen) profile. This is to ensure that the transplanted cells do not attack the patient’s tissues and cause graft-versus-host disease (GVHD). This could present as skin rash, impairment of liver function, or inflammation of the colon with severe diarrhea. Since there is always some minor mismatch between donor and recipient, the patient needs to take immunosuppressant drugs for at least a couple of months after transplantation in order to prevent GVHD.
There is one beneficial aspect of having a mild GVHD since the immune reaction carried out by the donors T lymphocytes against the diseased bone marrow then is believed to lower the risk of relapse. This is called graft-versus-leukemia effect (GVL). There are newer regimens in which doses of cytostatics and irradiation have been lowered in order to make use of the GVL effect by leaving a small part of the recipient’s bone marrow intact. An increasing number of patients are today getting a transplant from a sibling without full HLA match (haploidentical), thus facilitating the search for an acceptable donor. This is made possible by new techniques that decrease the risk of serious GVHD. The donor