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Bone marrow transplantation (BMT) as a source of hematopoietic stem cells is perceived as a powerful therapeutic regimen
that can potentially treat a variety of inherited and acquired diseases. BMT leading to mixed allogeneic hematopoietic
chimerism (MAC) can be used as an immunomodulatory approach to induce tolerance to auto-, allo-, and xeno-antigens for the
treatment of autoimmune disorders and prevention of foreign graft rejection. Mixed chimeras are tolerant to both donor and
host antigens since i) stem cells in the donor BM give rise to immune cells, such as lymphocytes, that are ?educated? in the host
immune environment for nonresponsiveness to the host antigens and ii) macrophages and dendritic cells arising from the donor
bone marrow serve as antigen-presenting cells in the thymus to eliminate donor reactive host lymphocytes. However, BMT
requires conditioning of recipients for effective engraftment and conditioning regimens used to establish MAHC in the clinic are
often toxic. The development of nontoxic and effective approaches to induce MAHC in the clinic, therefore, is of great scientific
and therapeutic pursuit. Towards this end, we have recently developed a novel approach, called ProtEx?, that allows us effective
and rapid engineering of bone marrow cells (BMCs) to display on their surface a modified apoptotic form of FasL protein.
Transplantation of these ?engineered? cells into allogeneic hosts was effective in establishing MAHC in recipients with minimal
conditioning and resulted in durable tolerance to donor grafts. Furthermore, this approach resulted in prevention of graft-vs-host
disease (GVHD), a major complication of BMT, by effectively eliminating mature T cells via apoptosis in the transplanted BMCs.
Engineering of total BMCs with exogenous immunomodulatory proteins serves as an effective, rapid, and clinically applicable
approach for the establishment of MAHC with significant clinical transplantation implications.
Esma S. Yolcu is Assistant Professor of Microbiology and Immunology and the Director of Imaging Facility at the Institute for Cellular Therapeutics
and member of James Brown Cancer Center, University of Louisville, Louisville, KY. Yolcu received her Ph.D. degree from the University of Ankara,
Ankara, Turkey. She joined the University Of Louisville School Of Medicine to pursue her postdoctoral training. Yolcu is the recipient of several
awards, member of various national and international societies, serves on Editorial Boards, and published over 67 peer-reviewed papers, abstracts,
and review articles in high ranking journals, such as Immunity, Circulation, and Journal of Immunology.
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