Abstract：
:Umbilical cord blood (CB) is a rich source of hematopoietic stem cells (HSCs) with important applications in allogeneic stem cell transplantation. However, the low numbers of hematopoietic stem and progenitor cells (HSPCs) in banked units remain a major limitation. Protocols developed for HSPC expansion ex vivo or to improve HSPC homing to the marrow represent solutions to overcome this shortcoming. In recent decades, wide arrays of functionally divergent approaches were developed for the amplification of HSPCs. These include optimization of cytokine cocktails, coculture systems, small molecules, and delivery systems for HSPC-expansion genes. Herein, we review past and current strategies, focusing on studies that characterize the contribution of expanded CB HSPC to short- and long-term engraftment in transplantation models or in clinical trials. Also discussed are homing effectors used to promote engraftment. In summary, these studies underscore that early-acting cytokines alone can expand HSPC with short-term engraftment activity, but that robust expansion of HSPCs with long-term engraftment necessitates the synergistic action of multiple HSC-expansion agonists. In support of this, early clinical trials based on cytokine-driven HSPC-expansion protocols delivered disappointing results, whereas recent trials based on the synergistic action of cytokines and HSPC-expansion agonists reported significant improvements in engraftment and therapeutic outcomes. Conversely, molecules that enhance homing of HSPC may represent a complementary approach to improve and perhaps accelerate engraftment. Optimization of the next generation of HSPC-expansion and priming strategies should support a paradigm shift in CB transplantation in which smaller, better matched units may preferentially be used.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Pineault N,Abu-Khader Adoi
10.1016/j.exphem.2015.04.011subject
Has Abstractpub_date
2015-07-01 00:00:00pages
498-513issue
7eissn
0301-472Xissn
1873-2399pii
S0301-472X(15)00162-9journal_volume
43pub_type
杂志文章,评审abstract：:Our main objective was to determine new factors associated with engraftment and single-unit predominance after double umbilical cord blood (UCB) allogeneic stem-cell transplantation. Engraftment occurred in 78% of cases in this retrospective study including 77 adult patients. Three-year overall survival, disease-free ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2014.07.264
更新日期：2014-11-01 00:00:00
abstract：:To understand the regulatory mechanisms involved in the development of hematopoietic stem cells, we cultured lineage-negative, c-Kit+ Sca-1+ stem cells sorted from bone marrow cells by a fluorescence-activated cell sorter (FACS) on layers of bone marrow stromal cell lines established from SV40 T-antigen gene transgeni...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
abstract：:Vascular endothelial cells can affect hematopoiesis by releasing granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, we show that GM-CSF production in murine aorta-derived vascular endothelial cells is regulated by two cytokines:interleukin-1 (IL-1), which induces the production of GM-CSF,...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:Two main aspects of the in vitro mouse foetal liver cell assay for Erythroid Stimulating Factor (ESF) in human sera have been investigated. The haem extraction process has been shown to give specific and quantitative recovery of 59Fe labelled haem from haemoglobin thus confirming that the material assayed in human ser...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1975-11-01 00:00:00
abstract：:Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results r...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.08.028
更新日期：2008-01-01 00:00:00
abstract：:Induction of fetal hemoglobin (HbF) is considered a promising strategy in the treatment of β-thalassemia, in which production of adult hemoglobin (HbA) is impaired by mutations affecting the β-globin gene. Recent results indicate that B-cell lymphoma/leukemia 11A (BCL11A) is a major repressor of γ-globin gene expressi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.08.011
更新日期：2015-12-01 00:00:00
abstract：:Normal and myeloid leukemic spleen cells from RF mice were cultured in vitro in plasma clots. In situ histochemical staining and karyotypic analysis of the colonies formed in the clot revealed that the colonies produced by leukemic and normal progenitors were indistinguishable morphologically and cytochemically. Colon...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-02-01 00:00:00
abstract：:During chronic hypoxia, the number of splenic erythroid progenitor cells in mice, particularly CFU-E, increased dramatically but transiently. Since all three classes of erythroid progenitors in the femoral bone marrow were suppressed, a large part of this increase might be attributed to migration of CFU-E and/or their...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-01-01 00:00:00
abstract：:Induced pluripotent stem cells (iPS) derived from disease cells are expected to provide a new experimental material, especially for diseases from which samples are difficult to obtain. In this study, we generated iPS from samples from patients with primary and secondary myelofibrosis. The primary myelofibrosis cells h...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：10.1016/j.exphem.2014.03.010
更新日期：2014-09-01 00:00:00
abstract：:The synthesis and expression of protein complexes of 23,000 and 30,00 dalton (p23,30) HLA-DR antigen, and of 44,000 and 12,000 dalton (p44,12) HLA-A,B antigen and beta 2-microglobulin was demonstrated on human peripheral blood monocytes and in cultures of purified, adherent monocytes. In indirect immunofluorescence as...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
abstract：:Coculture of cytotoxic T cells (STIL-3 C5) derived from L8313 leukemic mice with hematopoietic supportive stromal cells (MS-5) resulted in the detachment of MS-5 cells from the culture dish, whereas helper T cells (STIL-3 DF) did not induce this detachment. The response of bone marrow (BM) adherent cells to the same t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:Interferon α (IFNα) is used clinically to restore polyclonal hematopoiesis in patients with the myeloproliferative neoplasms polycythemia vera and essential thrombocythemia and to improve chemosensitivity in chronic myeloid leukemia patients. However, the mechanisms by which IFNα affects disease-initiating hematopoiet...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.05.013
更新日期：2015-10-01 00:00:00
abstract：:Bone marrow endothelial cells are likely to play an important role in the homing of hematopoietic progenitor cells. In view of analyzing the interactions between endothelial cells and hematopoietic progenitor cells, we studied several methods of isolating endothelial cells from human bone marrow, including fluorescenc...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Haploinsufficiency of erythroid Krüppel-like factor (EKLF/KLF1) has been shown recently to ameliorate the clinical severity of β-thalassemia by increased expression levels of fetal hemoglobin (HbF). The underlying mechanisms for role of EKLF in regulating HbF are of great interest but remain incompletely understood. I...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.03.004
更新日期：2018-07-01 00:00:00
abstract：:The development of a hematopoietic reporter is crucial for determining the fate of lineages derived from cell-based therapies. A marking system will enable safer embryonic stem and induced pluripotent stem cell-based derivation of blood lineages and facilitate the development of efficient cellular reprogramming strate...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2014.05.005
更新日期：2014-09-01 00:00:00
abstract：OBJECTIVE:It has been shown previously that infection with diverse viruses induces alterations in bone marrow lineage-specific progenitor cells. As complications arising from secondary bacterial infections can adversely affect the host, we investigated whether virally induced hematological alterations could contribute ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.09.005
更新日期：2005-12-01 00:00:00
abstract：:Previous systems for cloning human T-cells have been either one step procedures with small colony size (40 less than 40 cells) or two-step procedures with agglutination problems. These systems also require erythrocytes, thiols and human serum. We have regularly grown more than 10(3) colonies (more than 40 cells)/5 X 1...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-11-01 00:00:00
abstract：:Progress of age-related hematopoietic diseases such as myelodysplastic syndrome has previously been linked to enhanced levels of reactive oxygen species (ROS). Uncoupling protein 2 (UCP2) was found to reduce mitochondrial ROS production through uncoupling of the respiratory chain. The impact of UCP2 loss and elevated ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.08.003
更新日期：2016-11-01 00:00:00
abstract：:DNA methylation plays an important role in gene regulation. We have analyzed the methylation status of CCGG sites in and around the human proto-oncogene c-myc in blood cells from patients with acute and chronic leukemias and with myelodysplastic syndromes using restriction endonucleases. The 5' region of c-myc was une...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1992-10-01 00:00:00
abstract：:The proliferative capacity of partially purified populations of mouse bone marrow progenitor cells has been examined in serum-free cultures in the presence and absence of colony-stimulating factors (CSFs). The half-life of progenitor cells was approximately 25 h in the absence of factor, regardless of whether the fact...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：OBJECTIVE:Graft-versus-leukemia effects of donor lymphocytes have been considered to be central to the therapeutic benefit of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for malignant diseases. Surprisingly, some patients who reject donor grafts following nonmyeloablative HCT have sustained rem...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.04.022
更新日期：2006-09-01 00:00:00
abstract：OBJECTIVE:Hematopoietic stem cells (enriched in fraction of CD34+ cells) have the ability to regenerate hematopoiesis in all of its lineages, and this potential is clinically used in transplanting bone marrow or peripheral blood stem cells. Our objective was to assemble a suitable method for evaluating gene expression ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.04.006
更新日期：2006-07-01 00:00:00
abstract：OBJECTIVE:Our previous study has shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) gene/silica nanoparticles have a leukocytosis effect in normal dogs. Therefore, this study was conducted to determine whether treatment of canine GM-CSF gene/silica nanoparticles has preventive or therapeutic effects i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.04.002
更新日期：2008-09-01 00:00:00
abstract：:A cell line (LAMA-84) has been established from the blood of a patient with chronic myeloid leukemia in acute phase. LAMA-84 cells retained the patient's chromosome abnormalities, i.e., triplication of all chromosomes except chromosome 18, the presence of Philadelphia (Ph) chromosome in 4-5 copies, and the presence of...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-09-01 00:00:00
abstract：:It has been shown that in xenotransplantation of human cells into immunodeficient mice, the mouse strain background is critical. For example, the nonobese diabetic (NOD) strain is most efficient, the BALB/c is moderate, and the C57BL/6 is inefficient for human cell engraftment. We have shown that the NOD-specific poly...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.11.005
更新日期：2014-03-01 00:00:00
abstract：:This report presents the results of studies using long-term bone marrow cultures (LTBMC) of human bone marrow cells to investigate the effect of HIV-1 on in vitro hematopoiesis. Confluent stromal cell layers established from human bone marrow cells were irradiated to eliminate residual hematopoietic progenitor cells a...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:An unusual case of graft failure following bone marrow transplantation for aplastic anemia is reported in which the patient had delayed and incomplete recovery of hematopoiesis despite documentation of sustained engraftment. The pathophysiology of graft failure following bone marrow transplantation is discussed and re...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
abstract：:The mechanism of accelerated erythropoiesis under the hypoxic conditions of high altitude (HA) remains largely obscure. Here, we investigated the potential role of bone marrow (BM) T cells in the increased production of erythrocytes at HA. We found that mice exposed to a simulated altitude of 6,000 m for 1-3 weeks exh...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2014.04.007
更新日期：2014-09-01 00:00:00
abstract：OBJECTIVE:We previously showed that the organotellurium compound, ammonium trichloro (dioxyethylene-0-0') tellurate (AS101), has antitumoral activity in multiple myeloma (MM) cell lines. Here, we evaluated the antimyeloma activity of AS101 combined with low-dose melphalan, and also examined the activity of AS101 in the...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.01.006
更新日期：2009-05-01 00:00:00
abstract：:Remarkable advances have been made in bone marrow transplantation (BMT), which now has become a powerful strategy for the treatment of leukemia, aplastic anemia, congenital immunodeficiency disorders, and autoimmune diseases. Using various animal models, allogeneic BMT has been found to be useful in the treatment of a...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/s0301-472x(01)00645-2
更新日期：2001-06-01 00:00:00
