Thymus transplantation, a critical factor for correction of autoimmune disease in aging MRL/+mice.

Stem Cells and Development

Cui

et al. 2011

We have recently shown that allogeneic intrabone marrow-bone marrow transplantation þ adult thymus transplantation (TT) is effective for hosts with malignant tumors. However, since thymic and hematopoietic cell functions differ with age, the most effective age for such intervention needed to be determined. We performed hematopoietic stem cell transplantation (HSCT) using the intrabone marrow method with or without TT from fetal, newborn, and adult B6 mice ( CD44þ effector memory T cells and the production of interferon g (IFN-g) were highest in the mice treated with NLT þ NTT. These findings indicate that, at any age, HSCT þ TT is more effective against cancer than HSCT alone and that NLT þ NTT is most effective.

Section: Introductionmentioning

confidence: 74%

“…Newborn and fetal livers were obtained from the mice. Single-cell suspensions as newborn liver cells and fetal liver cells were prepared for use of HSCs [10]. For TT, AT, NT, and FT tissues were obtained from mice of the above ages.…”

Section: Hsct and Ttmentioning

confidence: 99%

Effects of Allogeneic Hematopoietic Stem Cell Transplantation Plus Thymus Transplantation on Malignant Tumors: Comparison Between Fetal, Newborn, and Adult Mice

Zhang

Stem Cells and Development

Cui

et al. 2011

“…12 We have also developed concurrent thymus transplantation (TT) with BMT; BMT plus TT was found to be effective for recipients showing thymic involution caused by aging, supralethal irradiation, chimeric resistance or malignant tumor. [13][14][15][16] However, it is unknown whether BMT plus TT is effective when using a nonmyeloablative regimen and/or when transplanting insufficient numbers of BMCs. In addition, TT has only been clinically applied to patients with DiGeorge syndrome or HIV infection who show hypoplasia of the thymus; 17,18 the effects of TT on BMT have not been extensively examined.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic intra-BM-BMT plus adult thymus transplantation from same donor has benefits for long-term survival even after sublethal irradiation or low-dose BM cell injection

Nishida

Takaki

et al. 2008

Bone Marrow Transplant

Self Cite

We examined the effects of intra-BM-BMT (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor after 5.5 Gy sublethal irradiation (SubLI) or lowdose (3 Â 10 6 ) BM cell injection (LDBMCI). With SubLI, BALB/c mice that had received 1 Â 10 7 bone marrow cells by IBM-BMT plus ATT from B6 mice showed 73% donor chimerism, whereas those treated with IBM-BMT alone showed 45% chimerism. In the LDBMCI with 7Gy irradiation, IBM-BMT plus ATT resulted in a 90% survival rate with 90% chimerism, whereas IBM-BMT alone resulted in a 55% survival rate with 44% chimerism. Although the number of CD4 T cells was higher in IBM-BMT plus ATT than in IBM-BMT alone, the percentages of FoxP3 þ /CD4 þ T cells and lymphocyte functions in the former were almost identical to those in the latter. When treated with IBM-BMT plus donor lymphocyte infusion (DLI), the mice showed a reduced survival time as a result of GVHD, with low numbers of FoxP3 þ CD4 T cells under either condition, although 100% chimerism was induced. These results suggest that IBM-BMT plus ATT is effective in reconstituting the recipients with donor-derived cells even after SubLI or LDBMCI.

“…We have previously reported that BMT plus thymus transplantation can accelerate hematopoietic recovery and improve survival rate, and can be used to treat autoimmune diseases in recipients such as aged or chimeric resistant hosts, 7,17 in which conventional BMT is difficult.…”

Section: Introductionmentioning

confidence: 99%

“…1 Using various animal models, we have found that allogeneic BMT can be used for the treatment of such diseases. [2][3][4][5][6][7][8][9] The basic theory is to replace pathogenic hematopoietic cells of hosts with normal hematopoietic stem cells (HSCs) of donors following lethal irradiation.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of newborn thymus plus hematopoietic stem cells can rescue supralethally irradiated mice

Ryu

Miyake

et al. 2008

Bone Marrow Transplant

Self Cite

We attempted to rescue supralethally irradiated (SLI) mice by transplantation of hematopoietic stem cells (HSCs) plus thymus from variously aged donors (fetus, newborn and adult). Although the transplantations of these kinds of HSCs alone showed a very short survival, newborn liver cells (NLCs) (as the source of HSCs) plus newborn thymus (NT) transplantation markedly improved the survival rate. The transplantation attenuated severe damage in the small intestine, which is one of the major causes of death by SLI. In addition, the donor-derived CD4 þ T cells significantly increased with additional NT transplantation. The production of interleukin (IL)-7 and keratinocyte growth factor, which plays a crucial role in protection against radiation injury in the intestine, was the highest in NT. Finally, SLI mice that had received NLC plus IL-7 À/À NT transplantation plus IL-7 injection showed improved survival, weight recovery and an elevated number of CD4 þ T cells compared with the mice that had received NLC plus IL-7 À/À NT or plus IL-7 injection alone. These findings suggest that NLCs plus NT transplantation can rescue SLI mice most effectively, and that high production of IL-7 in NT plays a crucial role with induction of CD4 þ T cells.