PMID- 11553851
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20131121
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 19
IP  - 5
DP  - 2001
TI  - A new method for tolerance induction: busulfan administration followed by 
      intravenous injection of neuraminidase-treated donor bone marrow.
PG  - 425-35
AB  - The portal venous (p.v.) administration of foreign cells induces donor-specific 
      tolerance. Recently, we have demonstrated that the p.v. administration of donor 
      cells elicits donor-specific tolerance across major histocompatibility complex 
      barriers. In the present study, utilizing the intrahepatic tolerance-inducing 
      system, we have established a new method for organ transplantation using both 
      busulfan ([Bu] to provide a sufficient "space" for the donor hematopoietic cells 
      to expand in the recipient) and neuraminidase ([Neu] to enhance the trapping of 
      i.v.-injected cells in the liver). Radiolabeled bone marrow cells (BMCs) were 
      found to exclusively accumulate in the livers of the recipients as a result of 
      the Neu treatment. Furthermore, hematopoietic progenitors (forming hematopoietic 
      foci) in the accumulated BMCs were retained in the recipient livers for at least 
      18 days. C57BL/6 (B6) mice that had been transplanted with skins of BALB/c mice 
      immediately after the injection of BALB/c BMCs showed a 90% skin graft survival 
      rate over 400 days as a result of using the combination of injecting 50 mg/kg Bu 
      into the B6 mice and treatment of the BALB/c BMCs with 0.25 U/ml Neu (50 Bu + 
      0.25 Neu). However, the survival rate significantly decreased when either the Bu 
      or Neu treatment was omitted. In tolerant recipients, microchimerism was observed 
      in the various hematolymphoid organs. T cells collected from the tolerant 
      recipients suppressed proliferative responses to the donor-alloantigens but 
      enhanced the production of Th2 and Th3 cytokines. These findings suggest that the 
      enhanced retention of donor BMCs in the recipient livers as a result of the Bu 
      and Neu treatments efficiently induces tolerance induction. Therefore, this 
      "single-day protocol" would be of great advantage for human organ 
      transplantation.
FAU - Nagahama, T
AU  - Nagahama T
AD  - The First Department of Pathology, Kansai Medical University, Osaka, Japan.
FAU - Sugiura, K
AU  - Sugiura K
FAU - Lee, S
AU  - Lee S
FAU - Morita, H
AU  - Morita H
FAU - Adachi, Y
AU  - Adachi Y
FAU - Kwon, A H
AU  - Kwon AH
FAU - Kamiyama, Y
AU  - Kamiyama Y
FAU - Ikehara, S
AU  - Ikehara S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - EC 3.2.1.18 (Neuraminidase)
RN  - G1LN9045DK (Busulfan)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells
MH  - Bone Marrow Transplantation/*methods
MH  - Busulfan/*administration & dosage
MH  - CD4-Positive T-Lymphocytes/metabolism
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis
MH  - Female
MH  - Immunosuppressive Agents/*administration & dosage
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Neuraminidase/*pharmacology
MH  - Skin Transplantation
MH  - Th2 Cells/metabolism
MH  - Time Factors
MH  - Transplantation Tolerance/*drug effects
EDAT- 2001/09/13 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/09/13 10:00
PHST- 2001/09/13 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/09/13 10:00 [entrez]
AID - 10.1634/stemcells.19-5-425 [doi]
PST - ppublish
SO  - Stem Cells. 2001;19(5):425-35. doi: 10.1634/stemcells.19-5-425.