Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.

Abstract

The purpose of this study was to evaluate human umbilical cord blood as an alternative to bone marrow in the provision of transplantable stem/progenitor cells for hematopoietic reconstitution. Although no direct quantitative assay for human hematopoietic repopulating cells is at present available, the granulocyte-macrophage progenitor cell (CFU-GM) assay has been used with success as a valid indicator of engrafting capability. We examined greater than 100 collections of human umbilical cord blood for their content of nucleated cells and granulocyte-macrophage, erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, in many cases both before and after cryopreservation. First it was determined that granulocyte-macrophage, erythroid, and multipotential progenitor cells remained functionally viable in cord blood untreated except for addition of anticoagulant for at least 3 days at 4 degrees C or 25 degrees C (room temperature), though not at 37 degrees C, implying that these cells could be satisfactorily studied and used or cryopreserved for therapy after transport of cord blood by overnight air freight carriage from a remote obstetrical service. Granulocyte-macrophage progenitor cells from cord blood so received responded normally to stimulation by purified recombinant preparations of granulocyte-macrophage, granulocyte, and macrophage colony-stimulating factors and interleukin 3. The salient finding, based on analysis of 101 cord blood collections, is that the numbers of progenitor cells present in the low-density (less than 1.077 gm/ml) fraction after Ficoll/Hypaque separation typically fell within the range that has been reported for successful engraftment by bone marrow cells. Another observation of practical importance is that procedures to remove erythrocytes or granulocytes prior to freezing, and washing of thawed cells before plating, entailed large losses of progenitor cells, the yield of unwashed progenitor cells from unfractionated cord blood being many times greater. The provisional inference is that human umbilical cord blood from a single individual is typically a sufficient source of cells for autologous (syngeneic) and for major histocompatibility complex-matched allogeneic hematopoietic reconstitution.

Biologic and phenotypic analysis of early hematopoietic progenitor cells in umbilical cord blood

“…tor cells at similar or higher frequency than that of BM. 1,[7][8][9]12 Therefore, UCB, which is normally discarded, has been evaluated as a source of progenitor cells that can be used for the treatment of diseases potentially curable by bone marrow transplantation (BMT). [2][3][4] Major concerns for wider transplant application of UBC have been related to the low total number of progenitor cells obtained by a single collection.…”

“…[1][2][3] Studies are under way to determine the feasibility of UCB banking for use in unrelated transplants. [3][4][5][6] However, the major concern for future transplant application in adult patients has been related to the low number of progenitor cells that could be obtained by a single UCB collection.…”

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

“…Early studies by Knudtzon [2] demonstrated that granulocytic colony-forming cells could be grown in vitro from UCB. Further in vitro studies by Broxmeyer et al [3] established that UCB contains a sufficient number of hematopoietic stem/progenitor cells to be used for autologous or allogeneic hematopoietic reconstitution. In 1989, Gluckman and colleagues published results from the first successful UCB transplant using cord blood from an HLAidentical sibling in a patient with Fanconii's anemia [4].…”

How can ethics relate to science? The case of stem cell research

“…In the most recent studies, research has been essentially based on the use of mesenchymal stem cells isolated from the umbilical cord blood, umbilical cord matrix and bone marrow. 17,18 However, it is important to highlight that there is still a long way to go in this area, and subsequent studies should demonstrate unequivocally (a) differentiation into functional somatic cells that integrate into existing tissues allowing recovery in vivo; (b) the non-formation of tumors; (c) the availability in sufficient number (and/or consequent expansion) of useful cells; and (d) that the results reported are reproducible in a variety of scientific and clinical settings (this has been a main cause of concern in the field).…”