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Hematopoietic Progenitor Cell Products Derived From Bone Marrow and Peripheral Blood
Hematopoietic stem cells (HSCs) are blood-forming multipotent stem cells that produce all blood cell lineages and maintain hematopoiesis. Hematopoiesis occurs in bone marrow (BM), but a small number of HSCs circulate in peripheral blood. Like other stem cells, HSCs have the capacity of self-renewal by means of asynchronous cell division, which produces an identical daughter stem cell and another cell, the progeny of which become terminally differentiated blood cells. Blood differs from other tissues in that it contains a multiplicity of cells that due to relatively short life spans (red blood cells [RBCs], 120 days; platelets, 1 week; granulocytes, less than 1 day) must be replaced daily. It is estimated that 10 × 10 12 cells are lost and replaced daily. Most HSCs remain quiescent in the BM. Their enormous proliferative capacity is accomplished by progeny destined to terminal differentiation. Progeny cells go through a series of divisions and maturation steps, each of which results in an amplification of the number of proliferating cells. HSCs are not morphologically identifiable but are identified by the glycoprotein cell surface antigen CD34 and their ability to “rescue” lethally irradiated recipients by engrafting and reconstituting the BM. Progeny of HSCs differentiate into Hematopoietic progenitor cells (HPCs). HPCs cannot self-renew, can differentiate and become restricted to a single lineage, are not morphologically identifiable, and are identified by the glycoprotein cell surface antigen CD34 and in vitro colony formation (colony-forming units [CFUs]). HPCs differentiate into morphologically identifiable precursors, which ultimately become mature blood cells that are released into the circulation. In general, adult stem cells, such as HSCs, compared with embryonic stem cells, have a limited capacity to differentiate; meaning they only differentiate into the tissues in which they reside and cannot dedifferentiate and become committed to other cell lineages. However, this distinction is becoming blurred by the use of HSCs to repair cardiac and neural tissue and the development of induced pluripotent stem cells (see Chapter 83 ).
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cell transplantation (HSCT) is the replacement of a recipient’s BM with donor HSCs. Historically, HSCT was referred to as bone marrow transplantation (BMT) because BM was the source of transplanted HSCs. HSCT is more accurate because HSCs can also be harvested from peripheral blood by apheresis and umbilical cord blood. Experimental HSCT began in the 1960s to treat BM failure related to lethal radiation exposure. Indications for HSCT include hematologic malignancies, BM failure syndromes, genetic disorders, such as hemoglobinopathies, and in conjunction with high-dose chemotherapy for a variety of malignancies. HSCT replaces abnormal and/or damaged HSCs to restore hematopoiesis and immunologic function and may also provide immunologic effects that help to eradicate malignancies and prevent relapse.
Hematopoietic Progenitor Cell Products
HPC products contain both HSC and HPC. Although HPCs may play a role in early engraftment, HSCs are required to sustain long-term engraftment. HPC products can be collected from BM (HPC, Marrow), peripheral blood by apheresis (HPC, Apheresis), and umbilical cord blood (HPC, Cord Blood; see Chapter 85 ). The HPC product’s total nucleated cell count (TNC) is used to determine the adequacy of the collection. Similarly, because HSCs and HPCs are both identified by the CD34 cell surface antigen, enumeration of CD34+ cells by flow cytometry, according the ISHAGE protocol, is used as a quality indicator for HPC products.
HPC, Marrow
BM is the physiologic site of hematopoiesis, and high concentrations of HSCs/HPCs can be collected from it. BM harvest is an invasive procedure involving aspiration from multiple sites on the iliac crest, performed in an operating room, requiring regional or general anesthesia. HPC, Marrow contains bone spicules, fat, and clots that should be filtered out during collection and/or processing. The weight of the recipient determines the number of cells required and volume collected. Generally, 10–15 mL of BM/kg recipient weight is collected, resulting in volumes of 1000–1500 mL for an average adult. Lymphocytes and granulocytes are the predominant cells with ∼0.5%–2% being CD34+ cells. HPC, Marrow hematocrits range from 20% to 30%, resulting in volumes of RBCs as great as 450 mL. When the donor and recipient are ABO/Rh incompatible it may be necessary to remove plasma and RBCs to prevent hemolytic reactions on infusion. Adverse events associated with BM harvesting are those associated with anesthesia, pain, bruising, and rarely infection at collection sites.
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