Stable mixed hematopoietic chimerism permits tolerance of vascularized composite allografts across a full major histocompatibility mismatch in swine
David W. Mathes
Division of Plastic Surgery, University of Colorado, School of Medicine, Denver, CO, USA
Search for more papers by this authorMario G. Solari
Division of Plastic Surgery, The University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Search for more papers by this authorGuy Scott Gazelle
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorPeter E. M. Butler
Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorAnette Wu
Transplantation Biology Research Laboratory MGH-East, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorAdam Nazzal
Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorGunnlauger P. Nielsen
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorChristene A. Huang
Transplantation Biology Research Laboratory MGH-East, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorDavid H. Sachs
Transplantation Biology Research Laboratory MGH-East, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorWei Ping Andrew Lee
Department of Plastic Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA
Search for more papers by this authorCorresponding Author
Mark A. Randolph
Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Correspondence
Mark A. Randolph MAS, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, WAC435, Boston, MA 02114, USA.
Tel.:617-726-6943;
fax: 617-726-8998;
e-mail: [email protected]
Search for more papers by this authorDavid W. Mathes
Division of Plastic Surgery, University of Colorado, School of Medicine, Denver, CO, USA
Search for more papers by this authorMario G. Solari
Division of Plastic Surgery, The University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Search for more papers by this authorGuy Scott Gazelle
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorPeter E. M. Butler
Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorAnette Wu
Transplantation Biology Research Laboratory MGH-East, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorAdam Nazzal
Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorGunnlauger P. Nielsen
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorChristene A. Huang
Transplantation Biology Research Laboratory MGH-East, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorDavid H. Sachs
Transplantation Biology Research Laboratory MGH-East, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorWei Ping Andrew Lee
Department of Plastic Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA
Search for more papers by this authorCorresponding Author
Mark A. Randolph
Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Correspondence
Mark A. Randolph MAS, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, WAC435, Boston, MA 02114, USA.
Tel.:617-726-6943;
fax: 617-726-8998;
e-mail: [email protected]
Search for more papers by this authorConflicts of interest:
The authors have declared no conflicts of interest.
Summary
This study tested the hypothesis that vascularized composite allografts (VCA) could be accepted in a robust model of hematopoietic chimerism by injecting allogeneic bone marrow cells (BMC) into swine fetuses. Outbred Yorkshire sows and boars were screened to ensure the absence of the major histocompatibility (MHC) allele SLAcc of inbred MGH miniature swine and then mated. Bone marrow harvested from an SLAcc swine donor was T-cell depleted and injected intravenously into the fetuses between days 50–55 of gestation. After birth, the piglets were studied with flow cytometry to detect donor cells and mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML) assays to assess their response to donor. Donor-matched VCAs from SLAcc donors were performed on four chimeric and two nonchimeric swine. The results showed donor cell engraftment and multilineage macrochimerism after the in utero transplantation of adult BMC, and chimeric animals were unresponsive to donor antigens in vitro. Both control VCAs were rejected by 21 days and were alloreactive. Chimeric animals accepted the VCAs and never developed antidonor antibodies or alloreactivity to donor. These results confirm that the intravascular, in utero transplantation of adult BMC leads to donor cell chimerism and donor-specific tolerance of VCAs across a full MHC barrier in this animal model.
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