Successful acceptance of adult liver allografts by intra-bone marrow-bone marrow transplantation.
ABSTRACT Previously, we have shown that liver allografts obtained from the fetus or young mice are accepted when bone marrow cells (BMCs) from adult mice of the same strain are co-grafted. However, for practical clinical use, it is more convenient to obtain both BMCs and liver from the same adult donors. C57BL/6 mice were irradiated with a single high-dose irradiation or two low-dose irradiations and injected with donor BALB/c (8 weeks old) BMCs intravenously (IV-BMT) or directly into the recipient BM cavity (IBM-BMT). Liver tissues taken from the same donor were, on the same day, engrafted under the kidney capsules. Higher survival rates and more complete reconstitution of donor cells were achieved in the IBM-BMT group than in the IV-BMT group, and this was the case in both irradiation protocols. The acceptance of donor liver tissue was seen in all mice in which hematolymphoid cells were replaced by donor-type cells. The liver grafts of the reconstituted mice showed normal morphology and stained positively with anti-albumin antibody and Periodic Acid Schiff (PAs) staining, indicating that the grafted livers were accepted, had grown, and were functioning. These results demonstrate that the acceptance of allogeneic liver can be achieved by cografting donor BMCs via the IBM route.
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ABSTRACT: The aim of this study was to assess the biological reactions triggered by stem cell transplantation related to phenotypic alteration, host-to-cell response, chromosomal stability, transcriptional alteration, and stem cell-like cell re-expansion. B6CBAF1 mouse embryonic stem cells (ESCs) were injected subcutaneously into homologous or heterologous (B6D2F1) recipients, and heterologous injections were performed with or without co-injection of B6D2F1 fetal fibroblasts. All homologous injections resulted in teratoma formation, whereas a sharp decrease in formation was detected after heterologous injection (100 vs. 14%; p<0.05). The co-injection of somatic cells in heterologous injections enhanced teratoma formation significantly (14 vs. 75%; p<0.05). Next, ESC-like cell colonies with the same genotype as parental ESCs were formed by culturing teratoma-dissociated cells. Compared with parental ESCs, teratoma-derived ESC-like cells exhibited significantly increased aneuploidy, regardless of homologous or heterologous injections. Repopulation of the parental ESCs was the main factor that induced chromosomal instability, whereas the co-injection of somatic cells did not restore chromosomal normality. Different genes were expressed in the parental ESCs and teratoma-derived ESC-like cells; the difference was larger with parental vs. heterologous than parental vs. homologous co-injections. The co-injection of somatic cells decreased this difference further. In conclusion, the host-to-cell interactions triggered by ESC transplantation could be modulated by co-injection with somatic cells. A mouse model using homologous or heterologous transplantation of stem cells could help monitor cell adaptability and gene expression after injection.PLoS ONE 09/2014; 9(9):e105975. DOI:10.1371/journal.pone.0105975 · 3.53 Impact Factor
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ABSTRACT: Bone marrow transplantation (BMT) is used to treat hematological disorders, autoimmune diseases (ADs) and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT) has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells (HSCs) but also mesenchymal stromal cells (MSCs). MSCs are multi-potent stem cells that can be isolated from bone marrow (BM), umbilical cord blood (UCB), and adipose tissue. MSCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of BM-derived-MSCs, and the treatment of intractable diseases such as rheumatoid arthritis (RA) and malignant tumors with IBM-BMT.Frontiers in Cell and Developmental Biology 09/2014; 2:48. DOI:10.3389/fcell.2014.00048
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ABSTRACT: Organ transplantation is useful for treating the end stage of organ failure. The induction of tolerance to the transplanted organ is essential for its long-term survival. Immunologic tolerance can be induced by immunosuppressive agents and mixed chimerism. Mixed chimerism is a state in which both recipient-and donor-derived blood cells remain in the hematopoietic system after allogeneic hematopoietic stem cells have been transplanted. Mesenchymal stem cells (MSCs), and immune cells such as dendritic cells and T-reg cells play an important role in the induction of tolerance. MSCs secrete cytokines, which modulate the immune response. In particular, they upregulate T-reg cell function and thereby induce tolerance. Intra-bone marrow-bone marrow transplantation recruits both donor-derived HSCs and MSCs, inducing persistent donor-specific tolerance without the use of immunosuppressants. In this review, we summarize the use of MSCs to induce tolerance in organ transplantation.Frontiers in Cell and Developmental Biology 03/2014; 2:8. DOI:10.3389/fcell.2014.00008