Chimerism最新文献

{"title":"A feasibility study on the prediction of acute graft-vs.-host disease before hematopoietic stem cell transplantation based on fetomaternal tolerance.","authors":"Masahiro Hirayama,&nbsp;Eiichi Azuma,&nbsp;Tsuyoshi Ito,&nbsp;Yoshitaka Keida,&nbsp;Yoshihiro Komada","doi":"10.4161/chim.24718","DOIUrl":"https://doi.org/10.4161/chim.24718","url":null,"abstract":"<p><p>The contact between the immune systems of mother and child during pregnancy affects an immune response of the child against noninherited maternal antigens (NIMA) and the mother against inherited paternal antigens (IPA). However, the immunologic effects of developmental exposure to NIMA or IPA are heterogeneous, and can be either tolerogenic or immunogenic. Although we have reported that prediction of acute graft-vs.-host disease (GVHD) is feasible in a murine model, there has been no literature in human. We devised a novel method for predicting a tolerogenic effect by using mixed lymphocyte reaction combined with enzyme-linked immunospot (MLR-ELISPOT) assay. The assay can evaluate reactivity of interferon-γ spot-forming cells of donor against the recipient. Although we have shown only two examples of mother to child reactivity so far, our preliminary results suggest that this pre-screened assay may be used to predict acute GVHD. The clinical trial is in progress to evaluate MLR-ELISPOT assay as a predicting measure of acute GVHD in haploidentical transplantation from NIMA or IPA-mismatched family donor. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 3","pages":"84-6"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.24718","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31495375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of treatment with DLA-identical or unrelated mesenchymal stromal cells in DLA-identical canine bone marrow transplantation.","authors":"Brian Kornblit,&nbsp;Wendy M Leisenring,&nbsp;Erlinda B Santos,&nbsp;Rainer Storb,&nbsp;Brenda M Sandmaier","doi":"10.4161/chim.25110","DOIUrl":"https://doi.org/10.4161/chim.25110","url":null,"abstract":"Background: Although in vitro and in vivo experiments have suggested that mesenchymal stromal cells (MSC) may have important immunomodulatory functions in allogeneic hematopoietic cell transplantation (HCT), results from clinical studies have been inconsistent. In the current study we investigate the safety of dog leukocyte antigen (DLA) identical or third party unrelated MSC in DLA-identical HCT. Results: There were no differences between treatment groups in depth of granulocyte or platelet nadirs, time to granulocyte or platelet engraftment, rate of acute GVHD or rejection. All dogs tolerated the MSC infusion well, although 2 dogs treated with unrelated MSC were euthanized on day 9 due to complications unrelated to the MSC infusion. While no formation of ectopic tissue was observed, GFP positive signals in bone marrow, spleen or liver were detected at time of necropsy in 75% and 50% of dogs treated with DLA-identical or unrelated MSC, respectively. Discussion: Treatment with DLA-identical or unrelated MSC in high dose DLA-identical HCT is safe, and provides a large animal HCT model in which to investigate immunological mechanisms and optimal treatment strategies for future human trials. Methods: Fourteen dogs were treated with 920 cGy total body irradiation (TBI) followed by transplantation of marrow from DLA-identical littermates and immunosuppression with cyclosporine. Prior to infusion of marrow, dogs received infusions of DLA-identical MSC from the marrow donor (n = 4), unrelated MSC (n = 4), or culture medium (n = 6), within 1 h of TBI. MSC obtained from relevant donors were ex-vivo expanded and transduced with GFP-retrovirus before infusion.","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 3","pages":"95-101"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.25110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31469511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimerism of bone marrow mesenchymal stem/stromal cells in allogeneic hematopoietic cell transplantation: is it clinically relevant?","authors":"Yasuo Miura,&nbsp;Satoshi Yoshioka,&nbsp;Hisayuki Yao,&nbsp;Akifumi Takaori-Kondo,&nbsp;Taira Maekawa,&nbsp;Tatsuo Ichinohe","doi":"10.4161/chim.25609","DOIUrl":"https://doi.org/10.4161/chim.25609","url":null,"abstract":"<p><p>Multipotent mesenchymal stem/stromal cells (MSCs) have been extensively used as a transplantable cell source for regenerative medicine and immunomodulatory therapy. Specifically in allogeneic hematopoietic stem cell transplantation (HSCT), co-transplantation or post-transplant infusion of MSCs derived from bone marrow (BM) of non-self donors has been implicated in accelerating hematopoietic recovery, ameliorating graft-vs.-host disease, and promoting tissue regeneration. However, irrespective of the use of MSC co-administration, post-transplant chimerism of BM-derived MSCs after allogeneic HSCT has been reported to remain of host origin, suggesting that the infused donor MSCs are immunologically rejected or not capable of long-term engraftment in the host microenvironment. Also, hematopoietic cell allografts currently used for HSCT do not seem to contain sufficient amount of MSCs or their precursors to reconstitute host BM microenvironment. Since the toxic conditioning employed in allo-HSCT may impair the function of host MSCs to maintain hematopoietic/regenerative stem cell niches and to provide a local immunomodulatory milieu, we propose that new directions for enhancing immunohematopoietic reconstitution and tissue repair after allogeneic HSCT include the development of strategies to support functional replenishment of residual host MSCs or to support more efficient engraftment of infused donor MSCs. Future areas of research should include in vivo tracking of infused MSCs and detection of their microchimeric presence in extra-marrow sites as well as in BM. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 3","pages":"78-83"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.25609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31602606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex chimerism: pregnancy after solid organ transplantation.","authors":"Kimberly K Ma,&nbsp;Margaret G Petroff,&nbsp;Lisa A Coscia,&nbsp;Vincent T Armenti,&nbsp;Kristina M Adams Waldorf","doi":"10.4161/chim.25401","DOIUrl":"https://doi.org/10.4161/chim.25401","url":null,"abstract":"<p><p>Thousands of women with organ transplantation have undergone successful pregnancies, however little is known about how the profound immunologic changes associated with pregnancy might influence tolerance or rejection of the allograft. Pregnant women with a solid organ transplant are complex chimeras with multiple foreign cell populations from the donor organ, fetus, and mother of the pregnant woman. We consider the impact of complex chimerism and pregnancy-associated immunologic changes on tolerance of the allograft both during pregnancy and the postpartum period. Mechanisms of allograft tolerance are likely dynamic during pregnancy and affected by the influx of fetal microchimeric cells, HLA relationships (between the fetus, pregnant woman and/or donor), peripheral T cell tolerance to fetal cells, and fetal minor histocompatibility antigens. Further research is necessary to understand the complex immunology during pregnancy and the postpartum period of women with a solid organ transplant. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 3","pages":"71-7"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.25401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31682193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A discussion of immune tolerance and the layered immune system hypothesis.","authors":"Jeff E Mold,&nbsp;Colin C Anderson","doi":"10.4161/chim.24914","DOIUrl":"https://doi.org/10.4161/chim.24914","url":null,"abstract":"Figure 1.Figure 1. Colin C. AndersonEssentially, the question being posed in the review of Mold and McCune1 is whether the fetal/neonatal immune system has special properties that predispose it to ...","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 3","pages":"62-70"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.24914","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31469515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microchimerism and allogeneic transplantation: we need the proof in the pudding.","authors":"Koen van Besien,&nbsp;Hong-Tao Liu,&nbsp;Andrew Artz","doi":"10.4161/chim.24358","DOIUrl":"https://doi.org/10.4161/chim.24358","url":null,"abstract":"Allogeneic stem cell transplantation (SCT) is the most effective treatment for leukemia and mediates its therapeutic effect to a large extent through immunologic effects, the so-called graft-vs-leukemia effects. Though highly effective it remains wrought with complications including opportunistic infections, graft vs. host disease as well as failure due to disease recurrence. Early animal experiments established that an HLA identical donor was a prerequisite for allogeneic SCT.1 But HLA-identical donors are elusive in societies where the number of siblings is decreasing and as scientists discover an ever larger number of HLA polymorphisms.2 Methods of transplantation that overcome HLA barriers are under intense investigation. HLA-mismatched Umbilical cord blood (UCB) is increasingly used as a source of stem cells for HLA-mismatched allogeneic stem cell transplantation (SCT) and has unique features that could be manipulated to advance the field. UCB-SCT causes limited GVHD, compared with cells from adult donors and relapse rates of leukemia are relatively low after UCB SCT, suggesting that UCB-SCT mediates GVL through mechanisms that are separate from those that cause GVHD.3,4 In our recent article we review recent data on fetal immunology and UCB SCT that provide a plausible explanation for this clinical observation.5 \u0000 \u0000It has long been known that exposure of a fetus to foreign antigens, be it from a fraternal twin, or from the mother can lead to lifelong tolerance.6,7 The low rate of GVHD associated with UBC SCT is reminiscent of this fetal tolerance and is perhaps best understood in the context of the makeup of the fetal immune system. Mold and McCune showed that the fetal immune system is dominated by T regulatory cells with suppressive activity.8 Fetal tolerance is most pronounced to maternal antigens and then specifically to the highly immunogenic non-inherited maternal HLA antigens or NIMAs.9 Van Rood et al. were the first to speculate that exposure of UCB grafts to an HLA mismatched transplant recipient whose mismatched HLA antigens were identical to the maternal NIMA antigens of the UCB would result in superior outcomes. Two large studies of different data sets support this hypothesis.10,11 Transplantation of an UCB graft into a mismatched recipient expressing NIMA, results in superior outcomes compared with transplant into a recipient who doesn’t express NIMA. \u0000 \u0000Another important aspect of the fetal immune system is the presence of maternal microchimeric cells.12 These maternal cells are sensitized to the fetal antigens of paternal origin, the so called IPA or inherited paternal antigens. Van Rood et al. again speculated that exposure to those IPA’s in a transplant recipient would allow the microchimeric maternal cells to target recipient cells. They provide powerful indirect evidence that this is indeed the case.13 Recipients whose HLA type includes the UCB donor’s IPA have a lower rate of disease recurrence than those whose HLA type ","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 3","pages":"109-10"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.24358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31321519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimerism 2013-Abstracts","authors":"","doi":"10.4161/chim.25046","DOIUrl":"https://doi.org/10.4161/chim.25046","url":null,"abstract":"","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"37 - 59"},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.25046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70621266","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":"Microchimerism in the human brain: more questions than answers.","authors":"William F N Chan,&nbsp;J Lee Nelson","doi":"10.4161/chim.24072","DOIUrl":"https://doi.org/10.4161/chim.24072","url":null,"abstract":"<p><p>Recently, our group reported the presence of microchimerism (Mc) in the human brain by performing quantitative PCR on female human brain tissues to amplify male DNA. We found brain Mc to be relatively frequent in humans and widely distributed in this organ. Our data also suggested a lower prevalence of brain Mc in women without Alzheimer disease than women without neurological disease. Altogether, these findings suggest that Mc could sometimes influence health and disease of the brain. As further research will be required to clarify this issue, here we discuss some of the questions that could be addressed to improve our understanding. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"32-3"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.24072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31259447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimerism and use of mesenchymal stem cells in umbilical cord blood transplantation.","authors":"Sofia Berglund,&nbsp;Michael Uhlin,&nbsp;Jonas Mattsson","doi":"10.4161/chim.24073","DOIUrl":"https://doi.org/10.4161/chim.24073","url":null,"abstract":"<p><p>We performed a retrospective single-center analysis of 50 umbilical cord blood transplantations (UCBTs), focusing on chimerism development. Complete donor chimerism (DC) was associated with acute graft-vs.-host disease (aGVHD) grades II-IV for the CD3 (+) cell lineage (p = 0.01) and, in multivariate analysis, with total body irradiation (TBI) for all lineages (p < 0.01). Overall survival (OS) was negatively associated with patient age, (p < 0.001); aGVHD grades III-IV, (p < 0.001); and treatment with mesenchymal stem cells (MSCs) (p = 0.027). In conclusion, though multiple factors may have contributed, the association of TBI and DC might be worthy of consideration in the treatment of patients with malignant disease in the UCBT setting. The negative influence of MSCs on OS may be a reason for more careful usage of this treatment modality in combination with UCBT. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"34-5"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.24073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31260551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of different blood sample processing methods for sensitive detection of low level chimerism by RHD real-time PCR assay.","authors":"Ahmad Javadi,&nbsp;Esther P Verduin,&nbsp;Anneke Brand,&nbsp;Henk Schonewille","doi":"10.4161/chim.24248","DOIUrl":"https://doi.org/10.4161/chim.24248","url":null,"abstract":"<p><p>The rhesus D blood group, which is expressed on the red blood cells (RBC) of 85% of the Caucasian population, is one of the most immunogenic RBC antigens, inducing D antibody formation in up to 20-80% of D-negative transfusion recipients and about 10% of pregnancies at risk. Pregnancy-induced D-antibodies can persist for many years, but the mechanisms underlying this persistence are unclear. The LOTUS study, a long-term follow-up study of mothers from severely affected children with hemolytic disease of the fetus and newborn investigates, among other endpoints, whether persistent feto-maternal chimerism is associated with long-term maternal anti-D persistence. We questioned which blood sample processing method should be used to detect low levels of RHD chimerism with the highest sensitivity and specificity using qPCR. After optimization of primer and probe concentrations for singleplex RHD exon 5 and 7 qPCR, sensitivity, specificity and efficiency of RHD and DYS1 qPCR were investigated in artificial chimeric samples. Sensitivity of DYS1 was one log higher (0.0001%) in enriched mononuclear cell fractions as compared with whole blood. Comparable linear sensitivity (0.007%) and mean efficiency (84-99%) for RHD qPCR were observed in all samples regardless whether whole blood or pre- or post-mixing of cellular fractions had been used. We conclude that RHD chimerism using singleplex exon 5 and 7 qPCR is linearly detectable down to 1.0 GE, without an advantage of fraction enrichment. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"9-14"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.24248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31414005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}