Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells
01 May 1989-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 86, Iss: 10, pp 3828-3832
TL;DR: 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.
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 1077 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
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TL;DR: To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches and PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.
Abstract: Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.
6,473 citations
TL;DR: It is necessary to select patients suitable for vaginal or laparoscopic mesh placement for Fanconi's anemia preoperatively on the basis of prior history and once they provide informed consent for surgery.
Abstract: The clinical manifestations of Fanconi’s anemia, an autosomal recessive disorder, include progressive pancytopenia, a predisposition to neoplasia, and nonhematopoietic developmental anomalies [1-3]. Hypersensitivity to the clastogenic effect of DNA-cross-linking agents such as diepoxybutane acts as a diagnostic indicator of the genotype of Fanconi’s anemia, both prenatally and postnatally [3-6]. Prenatal HLA typing has made it possible to ascertain whether a fetus is HLA-identical to an affected sibling [7]. We report here on hematopoietic reconstitution in a boy with severe Fanconi’s anemia who received cryo-preserved umbilical-cord blood from a sister shown by prenatal testing to be unaffected by the disorder, to have a normal karyotype, and to be HLA-identical to the patient. We used a pretransplantation conditioning procedure developed specifically for the treatment of such patients [8]; this technique makes use of the hypersensitivity of the abnormal cells to alkylating agents that cross-link DNA [9,10] and to irradiation [11] In this case, the availability of cord blood obviated the need for obtaining bone marrow from the infant sibling. This use of cord blood followed the suggestion of one of us that blood retrieved from umbilical cord at delivery, usually discarded, might restore hematopoiesis – a proposal supported by preparatory studies by some of us [12] and consistent with reports on the presence of hematopoietic stem and multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in human umbilical-cord blood (see the references cited by Broxmeyer et al. [12]).
2,055 citations
Cites background or methods or result from "Human umbilical cord blood as a pot..."
...* The preparation for the assays has been described elsewhere [12]....
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...This use of cord blood followed the suggestion of one of us that blood retrieved from umbilical cord at delivery, usually discarded, might restore hematopoiesis – a proposal supported by preparatory studies by some of us [12] and consistent with reports on the presence of hematopoietic stem and multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in human umbilical-cord blood (see the references cited by Broxmeyer et al. [12])....
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...Immediately after the birth of the patient‘s sister, blood was obtained from her umbilical cord and the placenta as described elsewhere [12] and transported at ambient temperature by overnight express service to a laboratory for cellular analysis, cryopreservation, and storage (Indiana University School of Medicine)....
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...Bone marrow and, under certain circumstances, the blood of adults (see references cited by Broxmeyer et al [12]) and the liver of fe- tuses [17] have been used in the transplantation of hematopoietic cells....
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...These values were within the range associated with successful transplantation of HLA–matched allogeneic bone marrow [12]....
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TL;DR: These studies describe a clonogenic method to define a hierarchy of EPCs based on their proliferative potential, and they identify a unique population of high proliferation potential-endothelial colony-forming cells (HPP-ECFCs) in human umbilical cord blood.
1,559 citations
TL;DR: Surprisingly, these cells were also able to differentiate into neuroglial- and hepatocyte-like cells under appropriate induction conditions and, thus, they may be more than mesenchymal stem cells as evidenced by their ability to differentiation into cell types of all 3 germ layers.
1,320 citations
TL;DR: A registry containing information on the outcome of cord-blood transplantation from 1988 to 1996 was established, and younger age, lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative serologic results in the recipient were favorable prognostic factors.
Abstract: Background Cord-blood banks have increased the use of cord-blood transplantation in patients with hematologic disorders. We have established a registry containing information on the outcome of cord-blood transplantation. Methods We sent questionnaires to 45 transplantation centers for information on patients receiving cord-blood transplants from 1988 to 1996. Reports on 143 transplantations, performed at 45 centers, were studied, and the responses were analyzed separately according to whether the donor was related or unrelated to the recipient. Results Among 78 recipients of cord blood from related donors, the Kaplan–Meier estimate of survival at one year was 63 percent. Younger age, lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative serologic results in the recipient were favorable prognostic factors. Graft-versus-host disease of at least grade II occurred at estimated rates of 9 percent in 60 recipients of HLA-matched cord blood and 50 percent in 18 recipients of HLA-misma...
1,245 citations
References
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TL;DR: 19 of 153 patients attending an early-synovitis clinic were shown to have been recently infected by the human parvovirus (HPV), and 5 other patients had evidence of some other closely preceding infection.
411 citations
TL;DR: From ten patients with advanced malignant disease involving the bone marrow, autologous hematopoietic stem cells were collected from the peripheral blood during eight four-hour pheresis procedures and cryopreserved to allow patients ineligible for bone marrow transplantation to receive marrow ablative therapy.
401 citations
TL;DR: The kinetics and pattern of hemopoietic reconstitution after myeloablative treatment and ABSCT provide clear evidence that blood-derived hemopuietic stem cells are capable of completely restoring hemopOietic function in man.
324 citations
TL;DR: Mouse marrow and spleen cells formed colonies consisting of 40-1,000 blast cells after 16 days of incubation in methylcellulose culture in the presence of medium conditioned by pokeweed mitogen-stimulated mouseSpleen cells provided an assay for the class of primitive hemopoietic progenitors described here.
Abstract: Mouse marrow and spleen cells formed colonies consisting of 40-1,000 blast cells after 16 days of incubation in methylcellulose culture in the presence of medium conditioned by pokeweed mitogen-stimulated mouse spleen cells. These colonies could be distinguished from other hemopoietic colonies in situ by the complete absence of signs of terminal differentiation. Replating of these colonies (tentatively named stem cell colonies) revealed their self-renewal capacity and the extensive ability to generate secondary colonies, many of which were multipotential hemopoietic colonies. Some of the colonies revealed 100% replating efficiencies. Analyses of individual stem cells colonies revealed concurrent and high incidences of spleen colony-forming units and the macroscopic granulocyte-erythrocyte-macrophage-megakaryocyte colony-forming units (CFU-GEMM) in culture. Replating comparison between the stem cell colonies and GEMM colonies strongly indicated that the progenitors for the stem cell colonies are higher in the hierarchy of stem cell differentiation than are CFU-GEMM. Quantitation of stem cell colonies provides an assay for the class of primitive hemopoietic progenitors described here.
320 citations
TL;DR: This human blast cell colony assay may provide a method for quantitation of more primitive hemopoietic stem cells than progenitors for GEMM colonies (CFU-GEMM) in man.
Abstract: We report identification of a unique class of human hemopoietic colony-forming cells with extensive ability to generate progenitors for secondary colonies. Mononuclear cells isolated from human umbilical cord blood formed colonies consisting of 40-500 blast cells after 25 d of incubation in methylcellulose culture in the presence of erythropoietin and medium conditioned by phytohemagglutinin-stimulated leukocytes. Replating of these blast cell colonies revealed that 100% of the primary colonies had the ability to generate secondary colonies, including multipotential colonies. These colonies could be distinguished from other hemopoietic colonies in situ by the complete absence of signs of terminal differentiation. Replating of granulocyte-erythrocyte-macrophage-megakaryocyte (GEMM) colonies, consisting of an average of 2 x 10(4) cells, revealed less capacity for secondary colony formation. This human blast cell colony assay may provide a method for quantitation of more primitive hemopoietic stem cells than progenitors for GEMM colonies (CFU-GEMM) in man.
312 citations