Harrison's Internal Medicine Chapter 68. Hematopoietic Stem Cells
Hematopoietic Stem Cells: Introduction All of the cell types in the peripheral blood and some cells in every tissue of the body are derived from hematopoietic (hemo: blood; poiesis: creation) stem cells. If the hematopoietic stem cell is damaged and can no longer function (e.g., due to the nuclear accident at Chernobyl), a person would survive 2–4 weeks in the absence of extraordinary support measures. With the clinical use of hematopoietic stem cells, tens of thousands of lives are saved each year (Chap. 108).
Developmental Biology of Hematopoietic Stem Cells
During development, blood cells are produced at different sites. Initially, the yolk sac provides oxygen-carrying red blood cells, and then several sites of intraembryonic blood cell production become involved. These intraembryonic sites engage in sequential order, moving from the genital ridge at a site where the aorta, gonadal tissue, and mesonephros are emerging to the fetal liver and then, in the second trimester, to the bone marrow and spleen.
Excess Capacity of Hematopoietic Stem Cells
In the absence of disease, one never runs out of hematopoietic stem cells. Indeed, serial transplantation studies in mice suggest that sufficient stem cells are present to reconstitute several animals in succession, with each animal having normal blood cell production. The fact that allogeneic stem cell transplant recipients also never run out of blood cells in their life span, which can extend for decades, argues that even the limiting numbers of stem cells provided to them are sufficient.
Several hematopoietic growth factors (HGFs) have achieved widespread clinical
application. In the United States alone, more than US $5 billion per year of the health care
budget is spent on these factors. The first patients were treated with recombinant human
erythropoietin (rHuEPO, epoetin alfa, Epogen®) in 1985 and the first patients received
recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF,
filgrastim, Neupogen®) or recombinant human granulocyte-macrophage colonystimulating
factor (rHuGM-CSF, sargramostim, Leukine® or Prokine®) in 1986.
Hierarchy of hematopoietic differentiation. Stem cells are multipotent cells that are the source of all descendant cells and have the capacity to provide either long-term (measured in years) or short-term (measured in months) cell production. Progenitor cells have a more limited spectrum of cells they can produce and are generally a short-lived, highly proliferative population also known as transient amplifying cells. Precursor cells are cells committed to a single blood cell lineage but with a continued ability to proliferate; they do not have all the features of a fully mature cell.
Some limited understanding of self-renewal exists and, intriguingly, implicates gene products that are associated with the chromatin state, a high-order organization of chromosomal DNA that influences transcription. These include members of the polycomb family, a group of zinc finger–containing transcriptional regulators that interact with the chromatin structure, contributing to the accessibility of groups of genes for transcription.
Complications Following Hematopoietic Cell Transplant
Early Direct Chemoradiotoxicities
The transplant preparative regimens commonly used cause a spectrum of acute toxicities that vary according to the specific regimen but frequently result in nausea, vomiting, and mild skin erythema (Fig. 108-1). Regimens that include high-dose cyclophosphamide can result in hemorrhagic cystitis, which can usually be prevented by bladder irrigation or with the sulfhydryl compound mercaptoethanesulfonate (MESNA); rarely, acute hemorrhagic carditis is seen.
Pneumocystis jiroveci pneumonia, once seen in 5–10% of patients, can be prevented by treating patients with oral trimethoprim-sulfamethoxazole for 1 week pretransplant and resuming the treatment once patients have engrafted.
The risk of infection diminishes considerably beyond 3 months after transplant unless chronic Most GVHD transplant develops, centers requiring recommend continuous continuing
trimethoprim-sulfamethoxazole prophylaxis while patients are receiving any immunosuppressive drugs and also recommend careful monitoring for late CMV reactivation.
Harrison's Internal Medicine Chapter Transplantation
Hematopoietic Cell Transplantation: Introduction
Bone marrow transplantation was the original term used to describe the collection and transplantation of hematopoietic stem cells, but with the demonstration that the peripheral blood and umbilical cord blood are also useful sources of stem cells, hematopoietic cell transplantation has become the preferred generic term for this process.
Chronic Leukemia Allogeneic hematopoietic cell transplantation is the only therapy shown to cure a substantial portion of patients with chronic myeloid leukemia (CML). Fiveyear disease-free survival rates are 15–20% for patients transplanted for blast crisis, 25–50% for accelerated-phase patients, and 60–70% for chronic phase patients, with cure rates as high as 80% at selected centers. Use of unrelated donors results in more GVHD and slightly worse survival than seen with matched siblings, although 3-year disease-free survival rates of 70% have been reported at some large centers.
Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài:
Phosphoproteomic analysis of apoptotic hematopoietic stem cells from hemoglobin E/b-thalassemia
All of the cell types in the peripheral blood and some cells in every tissue of the body are derived from hematopoietic (hemo: blood; poiesis: creation) stem cells. If the hematopoietic stem cell is damaged and can no longer function (e.g., due to the nuclear accident at Chernobyl), a person would survive 2–4 weeks in the absence of extraordinary support measures. With the clinical use of hematopoietic stem cells, tens of thousands of lives are saved each year (Chap. 108). Stem cells produce tens of billions of blood cells daily from a stem cell pool that is estimated to be...
Graft Failure While complete and sustained engraftment is usually seen posttransplant, occasionally marrow function either does not return or, after a brief period of engraftment, is lost. Graft failure after autologous transplantation can be the result of inadequate numbers of stem cells being transplanted, damage during ex vivo treatment or storage, or exposure of the patient to myelotoxic agents posttransplant. Infections with cytomegalovirus (CMV) or human herpes virus type 6 have also been associated with loss of marrow function.
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Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Ex vivo development, expansion and in vivo analysis of a novel lineage of dendritic cells from hematopoietic stem cells...