Crucial Role of Donor‐Derived Stromal Cells in Successful Treatment for Intractable Autoimmune Diseases in MRL/lpr Mice by BMT Via Portal Vein
| Autor: | Takashi Esumi, Naoya Ichioka, Taketoshi Kushida, Hirokazu Iida, Susumu Ikehara, Muneo Inaba, Hiroko Hisha, Ryokei Ogawa |
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| Rok vydání: | 2001 |
| Předmět: |
Mice
Inbred MRL lpr Time Factors Stromal cell Spleen Biology Peripheral blood mononuclear cell Autoimmune Diseases Mice medicine Animals Progenitor cell Radionuclide Imaging Vein Portal Vein Hematopoietic Stem Cell Transplantation Cell Biology Flow Cytometry Mice Inbred C57BL Disease Models Animal Haematopoiesis medicine.anatomical_structure Liver Immunology Leukocytes Mononuclear Cancer research Molecular Medicine Female Stromal Cells Stem cell Whole Bone Marrow Developmental Biology |
| Zdroj: | STEM CELLS. 19:226-235 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1634/stemcells.19-3-226 |
| Popis: | We have recently established a new bone marrow transplantation (BMT) method for the treatment of intractable autoimmune diseases in MRL/lpr mice; the method consists of fractionated irradiation (5.5 Gy × 2), followed by BMT of whole bone marrow cells (BMCs) from allogeneic C57BL/6 mice via the portal vein (abbreviated as 5.5 Gy × 2 + PV). In the present study, we investigate the mechanisms underlying the early engraftment of donor-derived cells in MRL/lpr mice by this method. In the mice treated with this method, the number of donor-derived cells possessing the mature lineage (Lin) markers rapidly increased in the BM, spleen, and liver; almost 100% were donor-derived cells by 14 days after the treatment. The number of donor-derived hemopoietic progenitor cells (defined as c-kit+/Lin− cells) increased in the BMCs, hepatic mononuclear cells, and especially spleen cells by 14 days after the treatment. Simultaneously, hemopoietic foci adjoining donor-derived stromal cells were observed in the liver when injected via the PV, but not via the peripheral vein (i.v.). When adherent cell-depleted BMCs were injected via the PV, recipients showed a marked reduction in the survival rate. However, when mice were transplanted with adherent cell-depleted BMCs with cultured stromal cells, all the recipients survived. These findings suggest that not only donor hematopoietic stem cells (HSCs) but also donor stromal cells administered via the PV were trapped in the liver, resulting in the early engraftment of donor HSCs in cooperation with donor-derived stromal cells. This new strategy to facilitate the early recovery of hemopoiesis would therefore be of great advantage in human application. |
| Databáze: | OpenAIRE |
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