Adding Bone-Forming Stem Cells to a BMT Doesn't Result in Better Outcomes So Far

[Guest guest]

[This study casts doubt upon the idea of using bone-forming stem

cells along with blood-forming stem cells in a stem cell transplant.

The hope was that adding these cells would enhance the transplant

while minimizing graft-v-host disease.]

Blood First Edition Paper, prepublished online May 11, 2006

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

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.

*These cells can be distinguished from the hematopoietic (blood-

forming) stem cells that are commonly used in stem cell transplants.