1.Research advances on microchimerism.
Xue-Dong SUN ; Jian-Li SANG ; Hui-Sheng AI
Journal of Experimental Hematology 2014;22(4):1153-1156
The microchimerism is a status of the microcell or DNA of an individual in another one with genetic differences. Taking an overall view about the discovery and research of the microchimerism, it was found that although the study of the microchimerism emphasizes the formation, origin, distribution, type, relationship to disease and several other aspects, the objects of the study are always the microchimerism that obtained naturally. As it is known to all, the microchimerism can also be produced in some clinical treatment, such as in the transplant and transfusion, but compared with the microchimerism gained naturally, obviously, the study for the iatrogenic microchimerism formed in the treatment is not elaborate enough. The curative effect of micro transplantation, a new technique for leukemia treatment, is obvious, but its mechanism is unclear, whether that is related to microchimerism still needs further research. This review summarizes the study history and perspective of the microchimerism so as to provide some ideas for studying the action mechanism of microchimerism in micro transplantation.
Chimerism
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DNA
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genetics
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Humans
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Transplantation Chimera
3.The Immune Tolerance Effect of Donor Chimerism Induced by Sublethal dose of Radiation on Allogeneic Organ Transplantation.
Jeong A KIM ; Sung Youl HONG ; Yun Seok CHOI ; Sung Hwan KIM ; Chun Choo KIM
Korean Journal of Hematology 2002;37(1):46-53
BACKGROUND: Transplantation of solid organs has been increasing explosively. However, numerous problems remain unsolved, including the requirement for chronic immunosuppressive therapy and the shortage of donor organs. Recently one way to overcome this is bone marrow transplantation after total body irradiation. Especially though the dose of radiation used for conditioning is decreased, allogeneic bone marrow cells are engrafted and it can induce donor specific tolerance for allografting. The aim of this study is to develop a nonlethal conditioning approach to achieve donor chimerism and to confirm donor specific tolerance in C57BL/6 mice. METHODS: We performed experiments on C57BL/6 mice divided into three groups according to preparatory radiation dosage. C57BL/6 mice received sublethal dose of radiation and transplanted with bone marrow cells from BALB/c. The percentage of donor derived cells was analyzed by flow cytometry (FACS) and the donor specific tolerance for allografts was assessed by BALB/c skin grafts and so did it by mixed lymphocyte reaction (MLR) and cytotoxicity (CML) using spleen cells from chimeras (BALB/c->C57BL/6). RESULTS: Induction of alllogeneic donor chimerism occurred in 50%, 100%, 100% of animals irradiated with 6Gy, 7Gy, and 9Gy TBI, respectively. One hundred percent of chimeras with evidence of donor chimerism accepted skin allografts. Moreover, mixed chimeras exhibited donor specific tolerance in vitro as assessed by MLR and CML. CONCLUSION: This strategy induced the donor chimerism and exhibited the donor specific tolerance effect for skin allografting.
Allografts
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Animals
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Bone Marrow Cells
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Bone Marrow Transplantation
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Chimera
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Chimerism*
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Flow Cytometry
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Humans
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Immune Tolerance*
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Lymphocyte Culture Test, Mixed
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Mice
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Organ Transplantation*
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Radiation Dosage
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Skin
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Spleen
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Tissue Donors*
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Transplantation, Homologous
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Transplants*
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Whole-Body Irradiation
4.Donor Bone Marrow Infusion in Deceased and Living Donor Renal Transplantation.
Gaetano CIANCIO ; George W BURKE ; Jang MOON ; Rolando Garcia MORALES ; Anne ROSEN ; Violet ESQUENAZI ; James MATHEW ; Yide JIN ; Joshua MILLER
Yonsei Medical Journal 2004;45(6):998-1003
The infusion and persistence in a transplant recipient of donor-derived bone marrow cells (DBMC) of multi-lineage can lead to a state of permanent chimerism. In solid vascular organ transplantation, the donor bone marrow lineage cells can even be derived from the transplant organ, and these cells can be detected in very small numbers in the recipient. This has been called microchimerism. Much controversy has developed with respect to the function of chimeric cells in organ transplantation. One idea is that the occurrence of these donor cells found in microchimerism in the recipient are coincidental and have no long-term beneficial effect on engraftment. A second and opposing view, is that these donor cells have immunoregulatory function that affect both the acute and chronic phases of the recipient anti-donor responses. It follows that detecting quantitative changes in chimerism might serve as an indication of the donor-specific alloimmune or regulatory response that could occur in concert with or independent of other adaptive immune responses. The latter, including autoimmune native disease, need to be controlled in the transplant organ. The safety and immune tolerance potential of DBMC infusion with deceased and living donor renal transplants was evaluated in a non-randomized trial at this center and compared with non-infused controls given identical immunosuppression. Overall DBMC infusions were well tolerated by the recipients. There were no complications from the infusion (s), no episodes of graft-vs-host disease (GVHD) and no increase infections or other complications. In the deceased DBMC- kidney trial, actuarial graft survival at 5 years was superior especially when graft survival was censored for recipient death. Acute rejections were significant reduced in patients given two DBMC infusions, and chronic rejection was dramatically reduced in all DBMC treated patients. The most interesting finding was that the degree of microchimerism slowly increased over the years the DBMC group that had exhibited no rejection episodes. In the DBMC-living related trial, the incidence of acute rejection did not differ between groups. However, DBMC chimerism in recipient iliac crest marrow had increased more rapidly than might be predicted from results previously seen in the cadaver group, despite four times fewer DBMC infused, with the generation of T- regulartory cells in-vitro assays.
*Bone Marrow Transplantation
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Humans
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*Kidney Transplantation
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*Living Donors
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*Tissue Donors
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*Transplantation Chimera
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*Transplantation Tolerance
5.Transfusion-associated microchimerism -- review.
Journal of Experimental Hematology 2009;17(1):247-250
Blood transfusion is a newly recognized cause of microchimerism, it seems to be common in severe traumatic injuries. In this review, the frequency, cause and prevention of transfusion-associated microchimerism (TA-MC), its current progress of knowledge and unanswered questions were summarized. In addition, the pregnancy-associated microchimerism and transplantation-associated microchimerism were discussed in this review.
Blood Donors
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Blood Transfusion
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Chimerism
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Humans
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Transplantation Chimera
7.Strategy Optimization and Clinical Analyze of Multiple Nucleotide Polymorphism Analysis in the Chimerism Detection after Allogeneic Hematopoietic Stem Cell Transplantation.
Zhe ZOU ; Rui SUN ; Yang-Wei LI ; Zhen GUO ; Rui-Hua FAN ; Xiao-Dong LYU
Journal of Experimental Hematology 2022;30(3):913-918
:
AbstractObjective: To investigate the sample selection, result correction and clinical application value of multi nucleotide polymorphism chimerism detection method based on Next-generation sequencing.
METHODS:
The chimerism samples from November 2018 to June 2020 were collected, and Pearson correlation coefficient (r) was used to analyze the consistency of bone marrow and peripheral blood results detected by MNPseq; according to the different information integrity before transplantation, the calibration model was constructed to analyze the correction value of the micro chimerism results in each model; the clinical results were retrospectively analyzed to verify the reliability and practicability of chimerism results correction and the clinical value of MNPseq method.
RESULTS:
The results of bone marrow and peripheral blood chimerism detected by MNPseq method were consistent with each other and showed significant correlation (r=0.985, P<0.01). The three groups of calibration models were constructed according to different pre-transplant information. For the no donor and pre-transplant patients information group, the correction value was 1%; while for the group with pre-transplant patients and without donor information, 0.61% of the chimerism rate and 13 heterotopic points were used as the correction value; 0.26% of the chimerism rate and 21.57% of the heterotopic points were used as the correction value for the group with pre-transplantation patients and donor information. After correction, the number of the patients with incomplete chimerism decreased from 276 (74.19%) to 141 (37.91%) (P<0.01). Among 18 (18/141, 12.77%) patients with incomplete chimerism, the results of MNPseq in the patients were 25-39 days earlier than those in STR and flow MRD, and the result showed statistical significance.
CONCLUSION
MNPseq method can be used to monitor chimerism with peripheral blood instead of bone marrow samples, and the results can be corrected to detect the changes of graft status in vivo in a more timely manner.
Chimerism
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Hematopoietic Stem Cell Transplantation
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Humans
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Nucleotides
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Reproducibility of Results
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Retrospective Studies
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Transplantation Chimera/genetics*
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Transplantation, Homologous
8.Clinical correlations of peripheral blood microchimerism after liver transplantation.
Kyung Mo KIM ; Eun Jung KIM ; Han Wook YOO ; Jong Jin SEO ; Sung Gyu LEE
Journal of Korean Medical Science 2000;15(3):260-264
The aim of this study was to evaluate microchimerism after human liver transplantation (LT). This study included 13 female recipients who received hepatic allograft from male donors at Asan Medical Center. A nested PCR specific for Y-chromosome gene (DYZ3) was used to analyze the small number of male cells in the peripheral blood mononuclear cells of the female recipients. Microchimerism was observed in 6 of 13 recipients and 16 out of 35 samples. Only 3 patients showed microchimerism 3 months after LT. There was no statistical difference between the presence of microchimerism and clinical findings such as type of donor, type of immunosuppression, episode of rejection and age of recipient. This study did not show any clinical relevance of microchimerism and further larger study are needed to confirm the results.
Adolescence
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Adult
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Animal
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Child
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Child, Preschool
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Female
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Human
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Infant
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Liver Transplantation*
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Lymphocytes/immunology*
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Male
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Transplantation Chimera/immunology*
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Transplantation Chimera/genetics
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Y Chromosome
9.Clinical correlations of peripheral blood microchimerism after liver transplantation.
Kyung Mo KIM ; Eun Jung KIM ; Han Wook YOO ; Jong Jin SEO ; Sung Gyu LEE
Journal of Korean Medical Science 2000;15(3):260-264
The aim of this study was to evaluate microchimerism after human liver transplantation (LT). This study included 13 female recipients who received hepatic allograft from male donors at Asan Medical Center. A nested PCR specific for Y-chromosome gene (DYZ3) was used to analyze the small number of male cells in the peripheral blood mononuclear cells of the female recipients. Microchimerism was observed in 6 of 13 recipients and 16 out of 35 samples. Only 3 patients showed microchimerism 3 months after LT. There was no statistical difference between the presence of microchimerism and clinical findings such as type of donor, type of immunosuppression, episode of rejection and age of recipient. This study did not show any clinical relevance of microchimerism and further larger study are needed to confirm the results.
Adolescence
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Adult
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Animal
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Child
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Child, Preschool
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Female
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Human
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Infant
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Liver Transplantation*
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Lymphocytes/immunology*
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Male
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Transplantation Chimera/immunology*
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Transplantation Chimera/genetics
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Y Chromosome
10.Short tandem repeat panel settled for quantitative chimerism analysis following allogeneic stem cell transplantation and its application.
Ying YANG ; Wen WU ; Ling-Ling WANG ; He-Ping CHEN ; Zi-Yan ZHU
Journal of Experimental Hematology 2009;17(3):706-712
To evaluate the roles of 8 short tandem repeats (STR) loci as STR panel in quantitative analysis of chimerism following transplantation, the primers were synthesized and marked with different dyes for D3S3045, D4S2366, D4S2639, D5S818, D13S317, D18S1002, D20S481 and D22S689. The blood samples of 15 cases received allogeneic stem cell transplantation were collected before and after transplantation, then DNA was extracted and amplified with these primers, and was further analysed under ABI Genetic Analyser 3100 to select suitable informative STR locus. Donor/recipient dilution series were prepared to get standard curves in selected loci, the DNAs extracted at different days after transplantation were used to quantitatively analyze the chimerism in patients according to the values of peak area or peak height of fluorescent signals. The standard curves can be used to calculate the chimerism by plotting the respective R/D quotient value against the percentage of recipient DNA. The results indicated that the calculated chimerism was in concordance with the donor/recipient dilution. The STR panel succeeded in identifying at least one informative marker and quantitative monitoring the chimerism after HSCT in 15 donor-recipient pairs and a relapsed case was diagnosed. It is concluded that the STR panel and its detection method can accurately and quantitatively monitor the chimerism after allogeneic HSCT, which is more economical and flexible than using commercial kits.
DNA
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genetics
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DNA Primers
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Hematopoietic Stem Cell Transplantation
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Humans
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Microsatellite Repeats
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Transplantation Chimera
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genetics