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Title: Lasting engraftment of histoincompatible bone marrow cells in dogs

Abstract

Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Radiobiological Inst. TNO, Rijswijk, Netherlands
OSTI Identifier:
6355364
Resource Type:
Journal Article
Resource Relation:
Journal Name: Transplantation; (United States); Journal Volume: 31:5
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 62 RADIOLOGY AND NUCLEAR MEDICINE; 59 BASIC BIOLOGICAL SCIENCES; BONE MARROW CELLS; TRANSPLANTS; BIOLOGICAL RADIATION EFFECTS; DOGS; DRUGS; GRAFT-HOST REACTION; LEUKEMIA; SPLEEN; WHOLE-BODY IRRADIATION; ANIMAL CELLS; ANIMALS; BIOLOGICAL EFFECTS; BODY; CONNECTIVE TISSUE CELLS; DISEASES; EXTERNAL IRRADIATION; HEMIC DISEASES; IRRADIATION; MAMMALS; NEOPLASMS; ORGANS; RADIATION EFFECTS; SOMATIC CELLS; VERTEBRATES; 560121* - Radiation Effects on Cells- External Source- (-1987); 550604 - Medicine- Unsealed Radionuclides in Therapy- (1980-); 550200 - Biochemistry

Citation Formats

Vriesendorp, H.M., Klapwijk, W.M., van Kessel, A.M.C., Zurcher, C., and van Bekkum, D.W.. Lasting engraftment of histoincompatible bone marrow cells in dogs. United States: N. p., 1981. Web.
Vriesendorp, H.M., Klapwijk, W.M., van Kessel, A.M.C., Zurcher, C., & van Bekkum, D.W.. Lasting engraftment of histoincompatible bone marrow cells in dogs. United States.
Vriesendorp, H.M., Klapwijk, W.M., van Kessel, A.M.C., Zurcher, C., and van Bekkum, D.W.. Fri . "Lasting engraftment of histoincompatible bone marrow cells in dogs". United States. doi:.
@article{osti_6355364,
title = {Lasting engraftment of histoincompatible bone marrow cells in dogs},
author = {Vriesendorp, H.M. and Klapwijk, W.M. and van Kessel, A.M.C. and Zurcher, C. and van Bekkum, D.W.},
abstractNote = {Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed.},
doi = {},
journal = {Transplantation; (United States)},
number = ,
volume = 31:5,
place = {United States},
year = {Fri May 01 00:00:00 EDT 1981},
month = {Fri May 01 00:00:00 EDT 1981}
}
  • Conditioning protocols were tested for their efficacy in increasing the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograftmore » rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-hr interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplo-type-mismatched donor. Possibilities for further improvement of this protocol are discussed.« less
  • We achieved long-term engraftment of unmatched bone marrow (BM) in dogs without graft-versus-host disease (GVHD) using a regimen of total lymphoid irradiation (TLI) which could be applied clinically. Twelve normal adult mongrel dogs were given TLI in 18 fractions of 100 rad each (total dose, 1800 rad) over 4 weeks to mantle and abdominal fields in continuity. Nine of the 12 were transfused with one or two random donor whole blood transfusions during the irradiation regimen to determine the risk of sensitization after the onset of immunosuppression. A mean (+- SD) of 0.71 +- 0.54 x 10/sup 9/ BM cells/kgmore » of recipient body weight from unrelated sex-mismatched donors was infused within 24 h of the 18th irradiation fraction. Engraftment was assessed by demonstration of donor-type sex chromosomes in spontaneous metaphase spreads of recipient marrow aspirates, and by the appearance of donor-type red blood cells antigens (DEA) in the recipients' blood. Three untransfused and nine transfused recipients were shown to be stable mixed BM chimeras during a followup period of 2 to 11 months after transplantation. Blood transfusion during TLI did not result in graft rejection. We observed no clinical signs of acute or chronic GVHD. TLI has minimal toxicity when compared with conditioning regimens currently used in BM transplantation for aplastic anemia. Potential advantages of the TLI regimen include the opportunity to use unmatched marrow donors and protection from GVHD.« less
  • Employing a new method for allogeneic bone marrow transplantation, irradiation chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant mice and AKR recipients were prepared. Though these chimeras had well-developed populations of T and B cells, they showed strikingly different patterns of responses in the primary antibody formation to sheep erythrocytes (SRBC), a T dependent antigen. These are (a) AKR mice treated with C57BL/10 cells, (B10 leads to AKR) fully H-2 incompatible, and AKR mice treated with B10.A (5R) cells, (5R leads to AKR) I-J,E compatible chimeras that were almost completely unresponsive to SRBC; (b) AKR micemore » treated with B10.BR cells (BR leads to AKR) fully H-2 compatible, and AKR mice treated with B10 AKM cells, (AKM leads to AKR) chimeras where donor and recipient differed only at H-2D, showed the same number of plaque-forming cells (PFC) as B10 control mice; (c) AKR mice treated with B10.A cells, (B10 leads to AKR) chimeras, where donor and recipient were matched at H-2K-I-E region, showed about one-half the number of PFC as the control mice. From these results we conclude that in allogeneic bone marrow chimeras primary antibody response to T-dependent antigen, such as SRBC, is generated when at least the K end of the H-2 complex is compatible between donor and recipient.« less