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Biology of Blood and Marrow... Mar 2011Engraftment syndrome (ES), typically characterized by noninfectious fever, rash, and/or noncardiogenic pulmonary edema, is a complication of autologous and allogeneic...
Engraftment syndrome (ES), typically characterized by noninfectious fever, rash, and/or noncardiogenic pulmonary edema, is a complication of autologous and allogeneic hematopoietic stem cell transplantation (HSCT). There are no data on ES after syngeneic HSCT. We retrospectively analyzed syngeneic HSCT outcomes and determined ES incidence, risk factors, and prognostic impact. Thirty-two adult patients with a median age of 46 years (range: 22-60) underwent syngeneic HSCT at our institution between July 1986 and April 2009, primarily for hematologic malignancies (65% lymphoid-including 15% plasma cell; 31% myeloid). The median duration of follow-up was 6.1 years (range: 3.7 months to 18.1 years). Five-year progression-free and overall survival (PFS, OS) was 52% and 67%, respectively. Five-year overall cumulative incidence of relapse and nonrelapse mortality (NRM) was 37.6% and 10.2%, respectively; with increased relapse incidence of 76.3% in myeloid disease (P = .002). Fifteen patients (47%) met diagnostic criteria for ES, 10 (67%) of whom received systemic steroids. Five-year PFS was 47% in patients with ES versus 56% in those without (P = .37). Five-year OS was 63% with ES versus 71% without (P = .80). Five-year cumulative incidence of NRM was 21% with ES versus 0% without (P = .06). Five-year cumulative incidence of relapse was 32% with ES and 44% without (P = .68). Older age (P = .05) and possibly total body irradiation-based conditioning (P = .09) were risk factors for developing ES. In multivariable Cox models only diagnosis (myeloid disease) impaired OS and PFS. In summary, we document a high incidence of ES after syngeneic HSCT. The trend of increased NRM after ES requires reevaluation in a larger syngeneic HSCT cohort.
Topics: Adult; Aging; Cohort Studies; Erythema; Female; Fever; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Leukemia, Myeloid; Male; Middle Aged; Prognosis; Pulmonary Edema; Recurrence; Retrospective Studies; Risk Factors; Survival Analysis; Syndrome; Transplantation, Isogeneic; Young Adult
PubMed: 20870027
DOI: 10.1016/j.bbmt.2010.09.013 -
Frontiers in Immunology 2017Donor-specific induced pluripotent stem cells (iPSCs) offer opportunities for personalized cell replacement therapeutic approaches due to their unlimited self-renewal... (Review)
Review
Donor-specific induced pluripotent stem cells (iPSCs) offer opportunities for personalized cell replacement therapeutic approaches due to their unlimited self-renewal potential and ability to differentiate into different somatic cells. A significant progress has been made toward generating iPSC lines that are free of integrating viral vectors, development of xeno-free culture conditions, and differentiation of pluripotent stem cells (PSCs) into functional somatic cell lineages. Since donor-specific iPSC lines are genetically identical to the individual, they are expected to be immunologically matched and these iPSC lines and their cellular derivatives are not expected to be immunologically rejected. However, studies in mouse models, utilizing rejection of teratomas as a model, have claimed that syngenic iPSC lines, especially the iPSC lines derived with integrating viral vectors, could be inherently immunogenic. This manuscript reviews current understanding of inherent immunogenicity of PSC lines, especially that of the human iPSC lines and their cellular derivatives, and strategies to overcome it.
PubMed: 28868053
DOI: 10.3389/fimmu.2017.00993 -
Journal of Orthopaedic Surgery and... Sep 2020Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer-irrigator-aspirator (RIA)... (Comparative Study)
Comparative Study
BACKGROUND
Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer-irrigator-aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.
METHODS
Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft, syngeneic iliac crest allograft, and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation, and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.
RESULTS
Although no differences were observed between groups in CT fusion mass volumes, iliac allografts displayed an increased number of radiographically fused fusion masses and a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow.
CONCLUSIONS
This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.
Topics: Allografts; Animals; Autografts; Bone Marrow Cells; Bone Transplantation; Cells, Cultured; Disease Models, Animal; Feasibility Studies; Female; Femur; Ilium; Lumbar Vertebrae; Osteogenesis; Rats, Inbred Lew; Spinal Fusion; Stem Cells; Tomography, X-Ray Computed
PubMed: 32933551
DOI: 10.1186/s13018-020-01936-8 -
BMC Genomics Jan 2020The clinical success of immune checkpoint inhibitors demonstrates that reactivation of the human immune system delivers durable responses for some patients and...
BACKGROUND
The clinical success of immune checkpoint inhibitors demonstrates that reactivation of the human immune system delivers durable responses for some patients and represents an exciting approach for cancer treatment. An important class of preclinical in vivo models for immuno-oncology is immunocompetent mice bearing mouse syngeneic tumors. To facilitate translation of preclinical studies into human, we characterized the genomic, transcriptomic, and protein expression of a panel of ten commonly used mouse tumor cell lines grown in vitro culture as well as in vivo tumors.
RESULTS
Our studies identified a number of genetic and cellular phenotypic differences that distinguish commonly used mouse syngeneic models in our study from human cancers. Only a fraction of the somatic single nucleotide variants (SNVs) in these common mouse cell lines directly match SNVs in human actionable cancer genes. Some models derived from epithelial tumors have a more mesenchymal phenotype with relatively low T-lymphocyte infiltration compared to the corresponding human cancers. CT26, a colon tumor model, had the highest immunogenicity and was the model most responsive to CTLA4 inhibitor treatment, by contrast to the relatively low immunogenicity and response rate to checkpoint inhibitor therapies in human colon cancers.
CONCLUSIONS
The relative immunogenicity of these ten syngeneic tumors does not resemble typical human tumors derived from the same tissue of origin. By characterizing the mouse syngeneic models and comparing with their human tumor counterparts, this study contributes to a framework that may help investigators select the model most relevant to study a particular immune-oncology mechanism, and may rationalize some of the challenges associated with translating preclinical findings to clinical studies.
Topics: Animals; CTLA-4 Antigen; Cell Line, Tumor; Colonic Neoplasms; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Genomics; Humans; Mice; T-Lymphocytes
PubMed: 31898484
DOI: 10.1186/s12864-019-6344-3 -
Drug Metabolism and Disposition: the... Dec 2011Triethylenetetramine (TETA) is an efficient copper chelator that has versatile clinical potential. We have recently shown that spermidine/spermine-N(1)-acetyltransferase...
Triethylenetetramine (TETA) is an efficient copper chelator that has versatile clinical potential. We have recently shown that spermidine/spermine-N(1)-acetyltransferase (SSAT1), the key polyamine catabolic enzyme, acetylates TETA in vitro. Here, we studied the metabolism of TETA in three different mouse lines: syngenic, SSAT1-overexpressing, and SSAT1-deficient (SSAT1-KO) mice. The mice were sacrificed at 1, 2, or 4 h after TETA injection (300 mg/kg i.p.). We found only N(1)-acetyltriethylenetetramine (N(1)AcTETA) and/or TETA in the liver, kidney, and plasma samples. As expected, SSAT1-overexpressing mice acetylated TETA at an accelerated rate compared with syngenic and SSAT1-KO mice. It is noteworthy that SSAT1-KO mice metabolized TETA as syngenic mice did, probably by thialysine acetyltransferase, which had a K(m) value of 2.5 ± 0.3 mM and a k(cat) value of 1.3 s(-1) for TETA when tested in vitro with the human recombinant enzyme. Thus, the present results suggest that there are at least two N-acetylases potentially metabolizing TETA. However, their physiological significance for TETA acetylation requires further studies. Furthermore, we detected chemical intramolecular N-acetyl migration from the N(1) to N(3) position of N(1)AcTETA and N(1),N(8)-diacetyltriethylenetetramine in an acidified high-performance liquid chromatography sample matrix. The complex metabolism of TETA together with the intramolecular N-acetyl migration may explain the huge individual variations in the acetylation rate of TETA reported earlier.
Topics: Acetylation; Acetyltransferases; Animals; Chromatography, Liquid; Liver; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mice; Mice, Inbred C57BL; Mice, Knockout; Trientine
PubMed: 21878558
DOI: 10.1124/dmd.111.041798 -
International Journal of Molecular... Apr 2020Due to their multifactorial aspects, mesenchymal stem cells (MSCs) have been widely established as an attractive and potential candidate for the treatment of a multitude... (Comparative Study)
Comparative Study
Due to their multifactorial aspects, mesenchymal stem cells (MSCs) have been widely established as an attractive and potential candidate for the treatment of a multitude of diseases. A substantial number of studies advocate that MSCs are poorly immunogenic. In several studies, however, immune responses were observed following injections of xenogeneic donor MSCs. In this study, the aim was to examine differences in immune responses exerted based on transplantations of xenogeneic, syngeneic, and allogeneic MSCs in the wild-type mouse brain. Xenogeneic, allogeneic, and syngeneic MSCs were intracerebrally injected into C57BL/6 mice. Mice were sacrificed one week following transplantation. Based on immunohistochemical (IHC) analysis, leukocytes and neutrophils were expressed at the injection sites in the following order (highest to lowest) xenogeneic, allogeneic, and syngeneic. In contrast, microglia and macrophages were expressed in the following order (highest to lowest): syngeneic, allogeneic, and xenogeneic. Residual human MSCs in the mouse brain were barely detected after seven days. Although the discrepancy between leukocytes versus macrophages/microglia infiltration should be resolved, our results overall argue against the previous notions that MSCs are poorly immunogenic and that modulation of immune responses is a prerequisite for preclinical and clinical studies in MSC therapy of central nervous system diseases.
Topics: Animals; Cells, Cultured; Female; Humans; Immunity; Leukocytes; Macrophages; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Microglia; Neutrophils; Transplantation, Heterologous; Transplantation, Homologous; Transplantation, Isogeneic
PubMed: 32357509
DOI: 10.3390/ijms21093052 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Jun 2021To evaluate the efficacy of syngeneic hematopoietic stem cell transplantation in the treatment of aplastic anemia. The clinic data of 11 patients with aplastic anemia...
To evaluate the efficacy of syngeneic hematopoietic stem cell transplantation in the treatment of aplastic anemia. The clinic data of 11 patients with aplastic anemia undergoing syngeneic HSCT were retrospectively analyzed. Among all of the 11 patients with AA, 4 males and 7 females were determined, with a median age of 22 (7-44) years old. All of the 11 patients achieved engraftment after the first transplantation: neutrophils engraftment occurred after a median of 10 days (range 8-23) , and platelet engraftment occurred after a median of 11 days (range 8-28) . Eight patients achieved long-term stable engraftment: three patients had graft failure, and two of them underwent secondary transplantation (1 case achieved long-term stable engraftment, but graft failure occurred again after hematopoietic reconstruction in another case) . The median follow-up time was 53 (5-135) months. All of the 11 patients survived, and the blood routine of 9 patients was normal for a long time. Syngeneic hematopoietic stem cell transplantation has a good long-term survival rate in the treatment of aplastic anemia, and graft failure is still the most significant problem.
Topics: Adult; Anemia, Aplastic; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Retrospective Studies; Transplantation Conditioning; Young Adult
PubMed: 34384153
DOI: 10.3760/cma.j.issn.0253-2727.2021.06.006 -
Transplantation Direct Jun 2019Membranes surrounding the fetus play a crucial role in providing a physical and immunological barrier between a semiallogeneic fetus and mother during pregnancy. In this...
BACKGROUND
Membranes surrounding the fetus play a crucial role in providing a physical and immunological barrier between a semiallogeneic fetus and mother during pregnancy. In this study, we tested whether cotransplantation of fetal membranes (FMs) and allogeneic donor cells would improve the retention and function of allografts in mice.
METHODS
Intact and enzyme-digested membranes obtained from E18-E19 pregnant mice were subcutaneously cotransplanted with 10F7MN hybridoma cells that are of BALB/cByJ (Balb) origin and secrete anti-human CD235a antibody. Cells were transplanted into C57BL/6J (B6, allogeneic), Balb (syngeneic), and FVB/NJ (third-party) mice. Serum was collected after 1 and 3 weeks of cell transplantation and tested using flow cytometry for the presence of anti-human CD235a antibody. Immunosuppressive functions of membranes were further investigated by analyzing the cytokine profile of supernatants collected from allo-reactive mixed lymphocyte reactions (MLRs) using a multiplex cytokine assay.
RESULTS
B6 mice transplanted with 10F7MN cells along with membranes syngeneic to the host had significantly higher levels of CD235a antibody when compared to B6 mice that received cells without membranes, allogenic membranes, or third-party membranes. Syngeneic membranes significantly inhibited T-cell proliferation in the presence of allogeneic stimuli and suppressed the release of Th1-cytokines such as IFNγ, TNFα, and IL-2 in MLRs. Additionally, increases in the levels of Th2-cytokines were found in MLRs containing membrane-derived cells.
CONCLUSIONS
Our study highlights the potential use of syngeneic FMs to act as potent cell-carriers that could improve graft retention as well as graft-specific immunoprotection during allograft transplantation.
PubMed: 31321294
DOI: 10.1097/TXD.0000000000000901 -
Drug Research Nov 2022Endometriosis is one of the most common gynecological diseases in women of reproductive age. Retrograde menstruation is considered a major reason for the development of...
Endometriosis is one of the most common gynecological diseases in women of reproductive age. Retrograde menstruation is considered a major reason for the development of endometriosis. The syngeneic transplantation mouse model is an endometriosis animal model that is considered to mimic retrograde menstruation. However, it remains poorly understood which genetic signatures of endometriosis are reflected in this model. Here, we employed an syngeneic mouse endometriosis model and identified differentially expressed genes (DEGs) between the ectopic and eutopic tissues using microarray analysis. Three gene expression profile datasets, GSE5108, GSE7305, and GSE11691, were downloaded from the Gene Expression Omnibus database and DEGs between ectopic and eutopic tissues from the same patients were identified. Gene ontology analysis of the DEGs revealed that biological processes including cell adhesion, the inflammatory response, the response to mechanical stimulus, cell proliferation, and extracellular matrix organization were enriched in both the model and patients. Of the 195 DEGs common to the model and patients, 154 showed the same expression pattern, and 28 of these 154 DEGs came up when PubMed was searched for each gene along with the terms "endometriosis" and "development". This is the first comparison of the DEGs of the mouse syngeneic endometriosis model and those of patients, and we identified the biological processes common to the model and patients at the transcriptional level. This model may be useful to evaluate the efficacy of drugs which target these biological processes.
Topics: Humans; Female; Mice; Animals; Gene Expression Profiling; Endometriosis; Cell Proliferation; Disease Models, Animal; Biological Phenomena
PubMed: 36055285
DOI: 10.1055/a-1894-6817 -
Indian Journal of Hematology & Blood... Oct 2018In spite of efforts, blood transfusion is still accompanied with adverse effects such as transfusion-related immunomodulation (TRIM). The current study aimed to evaluate...
In spite of efforts, blood transfusion is still accompanied with adverse effects such as transfusion-related immunomodulation (TRIM). The current study aimed to evaluate the effects of allogeneic, syngeneic, fresh and storage blood transfusion on the growth and metastasis of tumors and survival in fibrosarcoma bearing BALB/c mice. Twenty-five BALB/c mice were grouped into five groups of equal size. All groups were injected 1.2 × 10 WEHI-164 cells subcutaneously to induce fibrosarcoma tumor. After expansion of the tumor, in four groups (except for the control group), hemorrhage-induced anemia was developed. Twenty-four hours later, blood deficit was replaced by fresh allogeneic, storage allogeneic, fresh syngeneic and storage syngeneic blood transfusion, respectively. After a blood transfusion, for 13 days, the tumor size and survival of the mice were evaluated. In the day 20, the mice were sacrificed and their spleen tissues were evaluated for TRIM induced metastasis. Tumor size increase in the groups that received allogeneic (fresh and storage) and storage syngeneic blood transfusion was significantly higher than the control group ( value < 0.05). However, no significant difference was present in survival between the experiment groups and the control group. There was no metastasis in none of groups at the end of the study. Allogeneic and storage blood transfusion could have immunomodulatory effects such as increased tumor size. However, it seems that fresh and syngeneic blood transfusion have no effects on tumor growth in fibrosarcoma bearing mice. Further evidence may prove that more attention is warranted in blood transfusion into cancer cases.
PubMed: 30369743
DOI: 10.1007/s12288-018-0962-9