Research Group

  • Dr. Amelia Bartholomew, Principal Investigator
  • Dr. Pamela Witte, Research Associate
  • Dr. Anita Chong, Research Associate
  • Ms. Mandy Siatskas, Research Associate


  • University of Illinois at Chicago, Chicago, USA


  • The Role of Mesenchymal Stem Cells in Transplantation Tolerance

The induction of transplantation tolerance remains a foreseeable yet elusive goal in transplantation. Experimental approaches using donor bone marrow cells to eliminate recipient reactivity against donor organs are promising, but presently limited in appeal due to the need for rigorous recipient conditioning regimens. High doses of bone marrow stem cells can induce tolerance with less toxic conditioning regimens.

The success of this approach may be in part due to the increased frequency of other immunologically active cell types. Mesenchymal stem cells (MSCs) are multipotential cells that can be induced to differentiate into elements of the bone marrow microenvironment, such as bone cells, adipocytes, and stromal cells. Stromal progeny of MSCs have been implicated in regulatory signals that inhibit or promote lympho- and myelopoiesis, differentiation, and proliferation in vitro. When an extensive complement of MSC progeny, via bone fragments, is transplanted along with hematopoietic stem cells (HSCs), increased hematopoietic engraftment and transplantation tolerance have been observed. We have shown that transplantation of the bone marrow microenvironment without HSCs can lead to the permanent acceptance of murine cardiac allografts. Further, MSCs inhibit T cell proliferation in vitro, prolong skin graft survival, and home to the bone marrow compartment, thereby potentially influencing the host microenvironment. These observations have led us to hypothesize that MSCs have immunomodulatory properties and play a major role in the induction of transplantation tolerance.

In these studies, we will test whether MSCs directly affect the induction of tolerance by engrafting them within the thymus and altering the recipient T cell repertoire. We will also test whether the MSCs play an indirect role in the induction of tolerance through the facilitation of HSC engraftment either with or without host conditioning. Insights gained on the role donor MSCs play in allograft acceptance may then be applied to our pre-clinical model for the development of novel pre-clinical cellular therapies in transplantation tolerance.