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Blood, 15 September 2006, Vol. 108, No. 6, pp. 2114-2120.
Prepublished online as a Blood First Edition Paper on May 11, 2006; DOI 10.1182/blood-2005-11-011650.
 Previous Article | Next Article 
Submitted November 10, 2005
Accepted April 30, 2006
Donor-derived mesenchymal stem cells are immunogenic in an
allogeneic host and stimulate donor graft rejection in a
non-myeloablative setting
Alma J. Nauta*, Geert Westerhuis, Alwine B. Kruisselbrink, Ellie G.A. Lurvink, Roel Willemze, and Willem E. Fibbe
Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center
* Corresponding author; email: nauta{at}lumc.nl.
Mesenchymal stem cells (MSCs) are multipotent progenitor
cells that have emerged as a promising tool for clinical
application. Further clinical interest has been raised
by the observation that MSCs are immunoprivileged, and
more importantly, display immunosuppressive capacities.
These properties might be of therapeutic value in
allogeneic transplantation to prevent graft rejection
and for the prevention and treatment of graft-versus-
host disease. In the present study, we examined the in-
vivo immunomodulatory properties of MSC in murine models
of allogeneic bone marrow (BM) transplantation.
Sublethally irradiated recipients received allogeneic BM
with or without host or donor MSCs. Addition of host
MSCs significantly enhanced long-term engraftment
associated with tolerance to host and donor antigens.
However, infusion of donor MSCs was associated with
significantly increased rejection of allogeneic donor BM
cells. Moreover, we showed that injection of merely
allogeneic donor MSCs in naive mice was sufficient to
induce a memory T cell response. Although the observed
engraftment-promoting effects of host MSCs in vivo
support the therapeutical potential of MSCs, our results
also indicate that allogeneic MSCs are not intrinsically
immunoprivileged and that under appropriate conditions,
allogeneic MSCS induce a memory T cell response
resulting in rejection of an allogeneic stem cell graft.
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