are also susceptible to infections caused by Cytomegalovirus and Mycobacterium tuberculosis. The use of antibody drugs and tyrosine kinase inhibitors has refined the techniques used for HSCT. Secondary carcinogenesis is also a possibility that may arise late in patients who have undergone total-body irradiation or high-dose chemotherapy as a conditioning agent before the HSCT procedure.
HSCT is the only treatment option available for patients of adult, cerebral X-linked adrenoleukodystrophy. The disease is caused by progressive demyelination of the central nervous system, leading to neurologic decline and death in a few years. HSCT is safe for patients in whom the disease is not too advanced and, therefore, the patient’s condition needs to be evaluated carefully before planning the treatment.
HSCs have been the focus of attention for the last 50 years. However, the field has now been taken over by the iPSCs, which can generate patient-specific HSCs in unlimited numbers using controlled, regulated techniques. They will make the use of cord blood, bone marrow, and peripheral blood redundant and will impact regenerative and personalized medicine in a major way.
Ruby A. Singh
Independent Scholar
See Also: Blood Adult Stem Cell: Current Research on Isolation or Production of Therapeutic Cells; Blood Adult Stem Cell: Existing or Potential Regenerative Medicine Strategies; Blood Adult Stem Cell: Stem and Progenitor Cells in Adults.
Further Readings
Catacchio, Ivana, et al. “Evidence for Bone Marrow Adult Stem Cell Plasticity: Properties, Molecular Mechanisms, Negative Aspects, and Clinical Applications of Hematopoietic and Mesenchymal Stem Cells Transdifferentiation.” Stem Cells International, v.2013 (2013).
Copley, Michael R. and Connie J. Eaves. “Developmental Changes in Hematopoetic Stem Cell Properties.” Experimental and Molecular Medicine, v.45 (2013).
Doulatov, Sergei, Faiyaz Notta, Elisa Laurenti, and John E. Dick. “Hematopoiesis: A Human Perspective.” Cell Stem Cell, v.10 (2012).
Floria, Tögel and Christof Westenfelder. “Adult Bone Marrow-Derived Stem Cells for Organ Regeneration and Repair.” Developmental Dynamics, v.236 (2007).
Kent, David G., et al. “Prospective Isolation and Molecular Characterization of Hematopoietic Stem Cells With Durable Self-Renewal Potential.” Blood, v.113 (2009).
Blood Adult Stem Cell: Existing or Potential Regenerative Medicine Strategies
Blood Adult Stem Cell: Existing or Potential Regenerative Medicine Strategies
102
103
Blood Adult Stem Cell: Existing or Potential Regenerative Medicine Strategies
Regenerative medicine is a branch of medicine that focuses on the generation of viable cells, tissues, or organs or the use of cells to achieve a therapeutic outcome (e.g., to decrease inflammation in many disease processes). In response to the increasing burden of diseases caused by aging, trauma, sequealae (injury caused by disease or treatment), and congenital defects, new advances in regenerative medicine are paving the way for more effective treatments.
Current emphasis on stem cell therapies (embryonic and adult), a foundation for the generation of viable cells, tissues, and organs, has resulted in many new potential treatments. Because of the many ethical concerns in using embryonic stem cells, which are obtained from embryos, adult stem cells are at the forefront of recent studies ranging from bone marrow transplants in cancer patients and regeneration of cardiac tissue after myocardial infarction (MI-heart attack) to regrowth of bone in orthopedic disorders.
Adult Stem Cells
In contrast to embryonic stem cells, which are obtained from a developing embryo, adult stem cells are postnatal stem cells residing in the blood, bone marrow (BMCs), organs, and tissues. They are multipotent (limited differentiation potential) and can have a limited life span. Recently, scientists discovered that human adult stem cells derived from several sources (including blood) can be genetically reprogrammed to become the pluripotent equivalent of embryonic stem cells, with the ability to change into any cell type, thus potentially increasing the number of diseases that can be treated. Some disadvantages of using adult stem cells is a lack of guidelines on harvest volume of cells, timing in the course of a disease process to administer the cells, as well as optimal location of injection (e.g., heart muscle or vascular for cardiac injury). Additionally, stem cells harvested from an individual can carry harmful genetic mutations.
Specific blood-associated stem cells currently being used in Regenerative Medicine research are hematopoietic stem cells (HSC-bone marrow), mesenchymal stem cells (MSC-multiple tissues, including bone marrow and blood), and endothelial stem cells (ESC-bone marrow), and these are the most easily accessed. Some of these cells are also found in umbilical cord blood (UBCs), and these have many benefits. Foremost, if cord blood can be obtained at birth and stored (Cord Blood Registry), it provides a rich source of autologous stem cells that can be accessed in the event of disease or injury. Also, there is a reduced risk of developing graft-versus-host disease (GVHD), which commonly occurs in allogeneic transplants.
In addition to specific cells, there are important enzymes, growth factors, and other components present in stem cell-containing samples that serve to enhance the growth of target stem cells. An example of growth factor is granulocyte colony-stimulating factor (G-CSF). In particular, G-CSF has been used extensively to promote the mobilization or growth of certain stem cells in diseases such as cancer.
Existing Therapies in Regenerative Medicine
Bone marrow-derived stem cells have been in use since the 1960s for treatment of certain blood-related/bone cancers. The primary emphasis was placed on making sure healthy bone marrow could be restored after radiation or chemotherapy destroyed existing bone marrow. However, there are many caveats to receiving autologous (self-donor), allogenic (other donor), or, in rare cases, syngenic (twin donor) bone marrow transplants. First, though transplant rejection is minimized, autologous transplants carry the risk of reintroducing cancerous cells into the body after chemotherapy. Allogenic transplants reduce the potential for introducing mutated cells into the body but carry the potential for transplant rejection. Additionally, hematopoietic stem cells have been used to treat hematological dysfunctions and replenish bone marrow stores after chemotherapy.
A large number of recent studies have been performed on regeneration of cardiac tissue after trauma. After a functionally significant MI, patients can experience a loss of more than 1 billion cardiomyocytes, and surviving cardiomyocytes undergo abnormal remodeling, which eventually leads to heart failure. Current therapies such as medical management of hypertension and stent placement, to limit cardiac damage brought on by these and other cardiac complications, are often inadequate in optimizing cardiac health.
In 2012, the Cardiovascular Cell Therapy Research Network published results on the effect of timing of delivery of stem cell therapy after ST-segment elevation, an indication of heart attack. The BMCs or placebo were injected into the heart after a confirmed heart attack, either three or seven days after reperfusion (i.e., stent placement). Change in left ventricular function was evaluated after six months. They concluded that the time-course therapy did not result in a significant change on recovery or left ventricular function compared to placebo.
In
