Journal of hematotherapy & stem cell research最新文献

{"title":"Human mesenchymal stem cells are not of donor origin in patients with severe aplastic anemia who underwent sex-mismatched allogeneic bone marrow transplant.","authors":"Norbert Stute,&nbsp;Boris Fehse,&nbsp;Jens Schröder,&nbsp;Sönke Arps,&nbsp;Peter Adamietz,&nbsp;Karsten R Held,&nbsp;Axel R Zander","doi":"10.1089/152581602321080646","DOIUrl":"https://doi.org/10.1089/152581602321080646","url":null,"abstract":"<p><p>Stromal defects are part of the etiology of severe aplastic anemia (SAA), and hematopoietic engraftment is poor in unrelated and mismatched transplant. Therefore, we wanted to find out whether human mesenchymal stem cells (MSC) are partly of donor origin in patients with SAA years after successful bone marrow transplant (BMT). Three SAA patients 3, 5, and 8 years after BMT (cyclophosphamide, ATG) with bone marrow from an HLA-identical sibling donor of the opposite sex were investigated. MSC were grown from patients' bone marrow aspirates according to Caplan et al. The number of MSC that were isolated from SAA bone marrow post transplant was about 10 times lower than in normal controls. Primary cultures of adherent MSC and passage-one cells were analyzed by dual-color interphase fluorescence in situ hybridization (FISH) analysis using centromere-specific DNA probes for X and Y chromosome. FISH did not show any clear evidence of donor cells in the adherent MSC: In all cases, less than 0.5% of nuclei showed a donor-type signal pattern that is well within assay limits. In a female patient, the absence of male donor cells was confirmed by sensitive and quantitative, Y chromosome-specific TaqMan PCR (QYCS-PCR). In contrast, Ficoll-separated hematopoietic cells from the same aspirates were greater than 90% of donor origin, as expected. In SAA, as previously found in patients with lysosomal and peroxisomal storage disease, bone marrow MSC remain host-derived despite successful hematopoietic engraftment years after allogeneic BMT.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"977-84"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080646","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of ex vivo expansion and retrovirus-mediated gene transfer on primary T lymphocyte phenotype and functions.","authors":"Delphine Sauce,&nbsp;Nicolas Tonnelier,&nbsp;Anne Duperrier,&nbsp;Bruno Petracca,&nbsp;Marcelo de Carvalho Bittencourt,&nbsp;Mounir Saadi,&nbsp;Philippe Saas,&nbsp;Christophe Ferrand,&nbsp;Patrick Herve,&nbsp;Pierre Tiberghien,&nbsp;Eric Robinet","doi":"10.1089/152581602321080592","DOIUrl":"https://doi.org/10.1089/152581602321080592","url":null,"abstract":"<p><p>To modulate alloreactivity after hematopoietic stem cell (HSC) transplantation, suicide gene-expressing donor T cells can be administered with an allogeneic T cell-depleted HSC graft. Immune competence of such cells is a critical issue. We have examined the impact of our ex vivo gene transfer protocol (12-day culture period including CD3/IL-2 activation, retrovirus-mediated gene transfer, and G418-based selection) on the phenotype and functional properties of gene-modified cells (GMC). GMC were compared with control cells that had been cultured in parallel with GMC, but nontransduced and nonselected, as well as with peripheral blood mononuclear cells (PBMC). Our data show that phenotypical modifications are similar in control cells and GMC, demonstrating that alterations result from the 12-day culture rather than from the transduction and/or selection process itself. Such modifications include a reversal of CD4/CD8 ratio, activated phenotype (increased expression of CD45RO, CD95, and HLA-DR), and acquisition or increased expression of co-stimulatory molecules (CD80, CD86, and CD40). This led to an enhanced allostimulating potential of GMC, as compared with resting T cells, when used as stimulating cells in mixed lymphocyte reactions. Conversely, when using them as responder cells in mixed lymphocyte reactions, GMC exhibited a rapid loss of alloreactivity that resulted both from culture-dependent and from transduction and/or selection-dependent events. In conclusion, the retrovirus-mediated gene transfer can be associated with major phenotypical and functional alterations that could have strong clinical implications (increased immunogenicity, reduced anti-leukemic effect). Thus, future T cell expansion protocols should try to improve not only cell expansion or gene transfer efficiency, but also T cell functions.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"929-40"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080592","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular methods for detection and quantification of myeloma cells after bone marrow transplantation: comparison between real-time quantitative and nested PCR.","authors":"F Tögel,&nbsp;N Kröger,&nbsp;F Korioth,&nbsp;B Fehse,&nbsp;A R Zander","doi":"10.1089/152581602321080637","DOIUrl":"https://doi.org/10.1089/152581602321080637","url":null,"abstract":"<p><p>Multiple myeloma is characterized by malignant plasma cell-infiltration of bone marrow. Treatment with high-dose therapy results in a high rate of clinical remissions, but almost all patients ultimately relapse. Clinical staging and detection of relapse are limited in sensitivity. Therefore, we established molecular methods based on the highly clone-specific CDR regions of the immunoglobulin VH locus for sensitive and specific detection of residual myeloma cells after bone marrow transplantation. VDJ rearrangements were identified using a set of VH primers and a JH primer. Clone-specific rearrangements were detected by comparison with germ-line sequences. With the nested PCR approach, first-round amplification with the consensus primers was done followed by second amplification with myeloma-specific primers. The real-time quantitative PCR was performed using a myeloma-specific forward primer in combination with a JH consensus TaqMan probe and reverse primer. Sensitivity was tested using dilutions of myeloma cell lines into mononuclear cells. Nested PCR had a sensitivity of 10(-6) and TaqMan PCR of 10(-4) to 10(-5). Specificity was determined by testing different cell lines and patients' probes. These results were confirmed by follow up of 2 patients after allogeneic transplantation with dose-reduced conditioning. Molecular methods are very sensitive and specific tools for follow up of myeloma patients after allogeneic transplantation. By using the quantitative approach, it is possible to see kinetics of bone marrow tumor load, which can be used to guide therapeutic decisions like donor leukocyte infusions (DLI).</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"971-6"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mini-transplants turning micro: how low can we go?","authors":"Hans-G Klingemann","doi":"10.1089/152581602321080510","DOIUrl":"https://doi.org/10.1089/152581602321080510","url":null,"abstract":"","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"859-62"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiogenesis and plasticity: role of erythropoietin in vascular systems.","authors":"Zhao Zhong Chong,&nbsp;Jing-Qiong Kang,&nbsp;Kenneth Maiese","doi":"10.1089/152581602321080529","DOIUrl":"https://doi.org/10.1089/152581602321080529","url":null,"abstract":"<p><p>One of the principal functions of erythropoietin (EPO) is to stimulate the maturation of erythroid precursors. Yet EPO has recently been shown to modulate a host of cellular signal transduction pathways in pluripotent stem cells to perform multiple functions other than erythropoiesis. The production of EPO is tightly modulated by the loss of oxygen and the hypoxia-inducible factor 1. Once generated, EPO becomes a robust stimulus which regulates endothelial cell proliferation and migration as well as erythropoiesis and vascular resistance. Further downstream in the signal transduction cascade, EPO engages diverse cellular pathways--such as those involving Janus kinase 2, signal transducers and activators of transcription (STATs), mitogen-activated protein kinases (MAPKs), Bcl-x(L), protein kinase B, protein kinase C, and cysteine proteases--to provide \"plasticity\" to vascular systems through highly conserved mechanisms. EPO also has recently been demonstrated to inhibit the induction of apoptosis through two distinct components that involve the maintenance of the integrity of genomic DNA and the preservation of cellular membrane asymmetry. Recognition of the multipotential attributes of EPO for vascular systems may further the progress of the development of therapeutic strategies to delay the onset of degenerative diseases.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"863-71"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080529","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of high fluorescent reticulocytes in monitoring the aplasia outcome and optimizing the timing of peripheral blood stem cell harvesting.","authors":"Jean-François Lesesve,&nbsp;Bernard Lenormand,&nbsp;Francis Lacombe","doi":"10.1089/152581602321080664","DOIUrl":"https://doi.org/10.1089/152581602321080664","url":null,"abstract":"WE READ WITH INTEREST the Research Report “Automated immature reticulocyte counts are early markers of engraftment following autologous peripheral blood stem cell transplantation (PBSCT) in patients with lymphoma,” by George et al. (1). We would like to extend some claims, according to a 10-year experience of aplasia outcome monitoring using reticulocytes parameters as surrogate markers for the peripheral blood (PB) CD341 cell enumeration. The study (1) examined the reticulocyte parameters in an homogeneous group of 23 non-Hodgkin’s malignant lymphoma (NHL) patients, all treated with a single protocol (BEAM) before PB stem cell transplantation (SCT). Standard engraftment parameters—total white blood cell (WBC) count and absolute neutrophil count (ANC)— were measured together with reticulocytes. These last cells were determined using Methylene Blue and light scatter with an Abbott (Maidenhead, UK) automated counter, and divided into three fluorescence ratios with the high fluorescence reticulocytes (HFR) as the most immature cells. The recovery of the HFR to 2% of the total reticulocytes was significantly shorter when compared to the ANC at 0.5 3 109/L (median of 8 days vs. 10 days in 21 out 23 patients). The authors subsequently claimed that HFR measurement might be used as an early indicator of engraftment following PBSCT. Numerous studies have focused on reticulocyte assessment in hematological diseases. Nevertheless, reticulocyte studies dedicated to NHL patients are rare (2). Using the Sysmex R-1000 and 3000 devices (TOA Medical Electronics Ltd, Kobe, Japan), we also evaluated HFR counts in 10 patients affected by NHL and submitted to PBSCT after BEAM conditioning (3; unpublished data). During the leukopenic phase, only reticulocytes of low fluorescence ratio (LFR) at extremely low level (,10 3 109/L) were found. HFR counts declined to an undetectable level from days 11 to 13, and then became detectable and reached 5% of total reticulocyte count by day 10 (62). The ANC recovery achieved a value .0.5 3 109/L at day 111 (62). No correlation was found between HFR and PBSC yield; circulating CD341 cells were measured by flow cytometry, and colonyforming units granulocyte-macrophage (CFU-GM) measured by semisolid media assay. Hence, we agree that HFR gave advance notice of complete and stable hematopoietic engraftment as compared to traditional WBC and ANC counts. Immature reticulocytes succeeded in providing a realtime assessment of the functional state of erythropoiesis, and further to be a useful marker to predict hematopoietic recovery after treatment for severe aplastic anemia, chemotherapy for acute leukemias, and allogenic or autologous BMT (4). Moreover, HFR did not show transfusion support-related fluctuations. However, HFR is not widely used by the physicians for monitoring aplasia outcome after chemotherapy or SCT, or stem cell (SC) harvest timing. From this point of view, HFR failed to demonstrate its clinical value. In the BM transpla","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"987-9"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080664","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune recovery in breast cancer patients after tandem high-dose chemotherapy rescued by selected CD34+ cells.","authors":"Maurizio Lalle,&nbsp;Luca De Rosa,&nbsp;Annino Pandolfi,&nbsp;Rachele Amodeo,&nbsp;Angelo De Blasio,&nbsp;Aldo Montuoro,&nbsp;Luigi Marzetti","doi":"10.1089/152581602321080673","DOIUrl":"https://doi.org/10.1089/152581602321080673","url":null,"abstract":"TANDEM (TWO CONSECUTIVE CYCLES) high-dose chemotherapy with autologous hematopoietic stem cell support is a feasible treatment adopted as consolidation treatment for multiple myeloma, ovarian cancer, germ cell tumors, and also for high-risk and metastatic breast cancer. Since gene-marking studies of patients with hematological malignancy or neuroblastoma have showed that some relapses contain the markers of the reinfused cells (1,2), autologous CD341 cell-positive selection is performed with the intent to avoid tumor cell contamination of the grafts. Both dose-intensive chemotherapy with hematopoietic growth-factor support (3,4) and high-dose chemotherapy rescued by autologous bone marrow (BM) or peripheral blood progenitor cell (PBPC) transplant (5) can lead to immune damage, and immune reconstitution in adults showed a prolonged inversion of CD4/CD8 ratio, because of a long-lasting diminished number of CD41 cells. Positive selection of CD341 cells causes a further T cell depletion of the graft (by reducing residual mature T cells at negligible numbers) and can contribute to the post transplant lymphocyte regeneration delay (6). Decreased counts of CD41 lymphocytes in patients with hematological malignancies receiving high-dose chemotherapy rescued with selected CD341 cells are reported to increase the risk of opportunistic infectious diseases such as viral, fungal, or parasitic infections (7–9). We report our experience on the effects of a tandem course of high-dose chemotherapy as consolidation treatment rescued with CD341-selected cell transplants on immune reconstitution in breast cancer patients and evaluate the risk of opportunistic infectious complications in the early post-transplant. From November, 1997, to November, 1999, 12 patients (median age 40 years, range 31–57) with breast cancer not previously treated (7 high risk and 5 metastatic) received tandem high-dose chemotherapy as consolidation treatment after four cycles of FEC (5-Fluorouracil 600 mg/m2 i.v. on day 1; Epirubicin 90 mg/m2 i.v. on day 1; Cyclophosphamide 600 mg/m2 i.v. on day 1; every three weeks) regimen. Mobilizing treatment consisted of the same regimen supported by granulocyte-colony stimulating factor (G-CSF) 5 mc/kg per day s.c. from day 1 2 until end of aphereses. The threshold of 2 3 106/kg of CD341 cells to support each course of high-dose chemotherapy was requested. After collection, peripheral blood mononuclear cells were separated using a IBM 2991 cell separator and then underwent CD341 positive selection. In 6 patients, the capture method for CD341 cells was based on avidin-biotin immunoadsorption column Ceprate SC Stem Cell Concentration System, Cell Pro®; in the other 6 patients, the positive selection was based on immunomagnetic beads (Isolex 300i Magnetic Cell Separation System, Nexell®). Both systems were used according to the manufacturer’s specifications. After enrichment was completed, a median of CD341selected cells of 3.73 106/kg (range 2.1–8.8) f","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"991-4"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080673","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human colon adenocarcinoma in the SCID/CB6 radiation chimera is susceptible to adoptive transfer of allogeneic human peripheral blood mononuclear cells.","authors":"Fabian D Arditti,&nbsp;Ron Greenberg,&nbsp;Benjamin Dekel,&nbsp;Hadar Marcus,&nbsp;Arnon Nagler,&nbsp;Alain Berrebi,&nbsp;Yehuda Skornick,&nbsp;Yair Reisner","doi":"10.1089/152581602321080547","DOIUrl":"https://doi.org/10.1089/152581602321080547","url":null,"abstract":"<p><p>The aim of this study was to develop a murine model of human colon carcinoma (hCC) and to ascertain the potential of cellular immunotherapy in this model. Fragments of hCC obtained at surgery from 6 patients were transplanted under the kidney capsule of lethally irradiated CB6 mice radioprotected with severe combined immunodeficient (SCID) mice bone marrow. Tumor xenografts conserved their malignant behavior in the new environment, invading the mouse kidney parenchyma and expanding into the peritoneal cavity and adjacent tissues. Their growth was typically exponential, and they expanded to dimensions that allowed their subsequent fragmentation and passage to further preconditioned mice. Human carcinoembryonic antigen (hCEA) was detected on the implanted tumor and at occasionally spontaneous lung metastases. Most significantly, high levels of this tumor marker were detected in the sera of tumor-bearing mice, providing a useful tool, which allowed long-term experiments, monitoring of tumor progression, and its response to some treatment modalities. For instance, complete resection of the transplanted tumors, by means of nephrectomy, resulted in the disappearance of hCEA from mice sera within 2 weeks. Similarly, adoptive transfer of allogeneic human peripheral blood mononuclear cells (PBMC) into the peritoneum of tumor-bearing mice, resulted in their rapid engraftment, infiltration of tumor mass, and a significant drop of hCEA levels in mice serum, accounting for inhibition of tumor growth. We suggest that this novel model of human colon carcinoma affords the opportunity for in vivo evaluation of different preclinical treatment modalities, particularly, those involving manipulation with immune effector cells.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"883-93"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-1BB ligand stimulation enhances myeloid dendritic cell maturation from human umbilical cord blood CD34+ progenitor cells.","authors":"Young-June Kim,&nbsp;Geling Li,&nbsp;Hal E Broxmeyer","doi":"10.1089/152581602321080556","DOIUrl":"https://doi.org/10.1089/152581602321080556","url":null,"abstract":"<p><p>In humans, at least two subsets of dendritic cells (DCs) are identified on the basis of differential surface expression of CD11c antigens. CD11c(+) and CD11c(-) cells are respectively of myeloid and lympholoid origin and functionally distinct, eliciting inflammatory and tolerant T cell responses. We investigated whether 4-1BB ligand (4-1BBL), a member of the tumor necrosis factor (TNF) family, is involved in the maturation process to mature myeloid DCs during in vitro DC differentiation from immature DCs derived from human umbilical cord blood (CB) CD34(+) progenitor cells. Enhanced levels of CD11c as well as immunostimulatory molecules such as CD86, MHC class II, and 4-1BBL were induced in response to 4-1BBL stimulation. These changes were accompanied by noticeable morphological transition from nonadherent to adherent myeloid-like DCs. Stimulation of 4-1BBL on DCs with 4-1BB-Fc or with 4-1BB-transfected Jurkat cells resulted in acquisition of capacity for the immature DCs to produce interleukin-12 (IL-12). This suggests that 4-1BBL may be an important mediator for maturation of CD11c(+) myeloid DCs, information of possible relevance for the design of DC-based vaccines with enhanced activity.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"895-903"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080556","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematopoietic stem cell functional failure in interleukin-2-deficient mice.","authors":"J Chen,&nbsp;C M Astle,&nbsp;D E Harrison","doi":"10.1089/152581602321080565","DOIUrl":"https://doi.org/10.1089/152581602321080565","url":null,"abstract":"<p><p>The effects of interleukin-2 (IL-2) deficiency on hematopoiesis were tested by measuring cellular compositions in peripheral blood, spleen, thymus, and bone marrow of 3- to 5-month-old gene-targeted Il2 null (Il2(-/-)) mice using the Advia 120 Hematology system and fluorescence-activated cell staining (FACS). Il2(-/-) mice developed hematological failure and autoimmune responses, showing variable but significant degrees of anemia, lymphocytopenia, thrombocytopenia, splenomegaly, thymus involution, and weight loss. Surprisingly, Il2(-/-) mice had normal numbers of bone marrow cells (BMCs) with increased numbers of Lin(-)Kit(+)Sca1(+)CD34(-) and Lin(-)Kit(+)Sca1(+)CD34(+) cells that are normally associated with hematopoietic stem cells (HSCs) and progenitor cells. Day-12 colony-forming units-spleen cells were slightly reduced in Il2(-/-) mice. When Il2(-/-) and Il2(+/+) mice were compared for long-term HSC function in vivo in the competitive repopulation assay, BMCs from Il2(-/-) donors had 10- to 20-fold less HSC repopulating ability, which affected both myeloid and lymphoid cell lineages. Thus, HSCs from Il2(-/-) mice can proliferate normally but are functionally defective for reconstituting lethally irradiated recipients.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"905-12"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080565","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}