Floor plan - 2013 Annual Meeting - American Association for Hand ...

The Role of Thymus in Chimerism Induction on Composite Osseomusculocutaneous Sternum,
Ribs, Thymus, Pectoralis Muscles, Skin Allotransplantation Model
Institution where the work was prepared: Cleveland Clinic, Cleveland, OH, USA
Mehmet Bozkurt, MD; Serdar Nasir; Aleksandra Klimczak; Lukasz Krokowicz; Christopher Grykien; Maria Siemionow;
Cleveland Clinic
INTRODUCTION:
Cellular and vascularized bone marrow may supply donor derived hematopoietic cells, and both have been used to induce donor-specific
chimerism in various models of vascularized bone marrow transplants. We are introducing a new composite vascularized sternal bone marrow
transplant model which can be applied for augmentation of hematopoietic activity for chimerism induction after transplantation.
METHODS:
Ten allograft transplantation were performed between Lewis-Brown Norway (LBN,RT11+n) donors and Lewis (RT1l) recipients. Group I
consisted of 5 allograft transplantation via osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, skin. In Group II 5 allografts
transplantation were performed using osseomusculocutaneous sternum, ribs, pectoralis muscles, skin without the thymus (Fig 1).
Sternum and the costal ribs were harvested based on the common carotid artery and internal jugular vein. In the recipient Lewis (RT1
l), harvested isograft transplants were transferred into the inguinal region and anastomosis was performed between carotid, jugular and
femoral pedicles (Fig 2). All animals received tapered dose of CsA therapy. Presence of donor orgin cells in the peripheral blood of
recipients was evaluated by flow cytometry using monoclonal antibodies specific for donor MHC class I.
RESULTS:
Longest survival is 120 days post transplanted and are still under observation (Fig 3-4 early/long survival view). All sternal grafts have
survived and flap viability was observed daily via inspection of skin island. This composite graft carried 5x106 of hemoetopeotic cells.
Donor specific chimerism was detected during follow up period and introduced as a sum of donor T cell, B cells and monocyte/
macrophage/ dendiric cells. At day 7 post transplant total level of chimerism was assessed at 3.8% of RTIn positive cells and increased
to 13.2% at day 63 post transplant. In contrast in group II (without thymus) initial chimerism at day 7 was evaluated at 0.3% and increased
to 2.4% at day 21 post-transplant (still under observation). Donor orgin cells were also detected in the bone morrow compartment of
recipient at 4.21% of RTIn positive cell cells. Chimerism will be monitored during follow-up period.
CONCLUSIONS:
We have introduced a new model of composite vascularized bone marrow transplantation by sternal allograft which does not require
laparotomy for the placement of the bone. This graft carries significant amount of bone marrow within intact microanotomical compartment.
In this model long term survival correlated directly with chimerism level. Furthermore long term survival of the composite allograft
via thymus is imperative for induction of high level of donor specific chimerism.
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