Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 146

Since the bone marrow is rich in blood stem cells, it is transplanted to treat disorders of the blood, such as leukemia, lymphoma, or multiple myeloma, as well as genetic disorders. Small quantities of blood stem cells obtained from the UCB can be used to treat leukemia, congenital immunodeficiencies, anemias, or sickle cell disease in children. This is known as stem cell therapy.

Transplantation of adult blood stem cells into a new environment is a complex process with several success-limiting steps. The transplanted HSCs must first migrate from the peripheral circulation to the bone marrow niches. This process is known as homing. They need to be successfully lodged at the site, a process which requires adherence and retention. The freshly transplanted cells interact with the extrinsic components of the niche, which will dictate their stability and future course of action. It is expected that homing and lodging in the appropriate microenvironment will dictate the clinical outcome of the bone marrow transplantation.

Studies have shown the necessity of the calcium-sensing receptor in the process of lodging and engraftment in the bone marrow niche. Stimulation of the receptor also leads to augmented homing. It follows that ex vivo modulation of the calcium-sensing receptors with calcimimetics can be used to increase the success rate of the transplants. Other cell-adhesion molecules, such as α4 integrins, hyaluronic acid, and osteopontin present on the cell surface promote interaction with the components of the niche and are instrumental in retaining the HSCs in the niche. The signaling cues originating in the niche direct the self-renewal or differentiation pathways in the lodged HSCs, depending on the requirement of the hematopoietic system of the recipient.

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered a viable option for the treatment of adult T-cell leukemia. Even patients who had not gone into complete remission were assured of long-term survival after allogeneic HSCT. Advances have also been made in HSCT for childhood and adolescent lymphomas. Ironically, even though the treatment works, the mortality due to infections and organ failure is high and needs to be reduced. Complications in allogeneic HSCT may arise because of treatment-related toxicity, graft-versus-host disease, as well as infections. The range of infections in HSCT patients includes invasive pneumococcal disease, urinary tract and surgical site infection, peritonitis, bacteremia, septic shock, and infection of indwelling medical devices. Bacteremia caused by the presence of bacteria in the blood is a complication in almost 20 percent of patients. Staphylococcus species and Escherichia coli were commonly linked to the infection in blood.

Patients 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.