Characterizing vascular smooth muscles in intimal hyperplasia during vascularized composite allotransplantation

Vascularized composite allotransplantation (VCA) is the transplantation of composite tissue as a single unit.  Both acute and chronic rejection is inevitable during VCA, albeit in the presence of immunosuppression. Rejection is associated with graft vasculopathy and typically identified with intimal hyperplasia (IH) in blood vessels.

The Plock laboratory at UZH has established an in vivo model of VCA with allogenic hind limb transplantation in rats. In this model, acute and chronic rejection was achieved by transplanting hind limbs from Brown Norway to Lewis rats (complete mismatch) and from Fischer to Lewis rats (partial mismatch), respectively. Histological analysis of the transplanted tissue at rejection revealed typical features of IH as observed in the clinics. The participating inflammatory pathway during this pathology is an ongoing study in the laboratory. Simultaneously, understanding the mechanism of IH is pivotal to develop strategies to attenuate IH in VCA.

During IH, vascular smooth muscle cells (SMCs) accumulate in the intima where they switch from a contractile to a synthetic phenotype, proliferating and producing extracellular matrix components. The Bochaton-Piallat laboratory at UniGE, extensively compares, at a molecular level, the characteristic features of SMCs during atherosclerosis, a pathology that also involves IH.

The main goal of this collaboration is to mitigate IH, lowering graft vasculopathy and thereby attenuating rejection in VCA. This will be achieved by bringing together the expertise of Bochaton-Piallat laboratory in characterizing SMCs during IH and that of Plock laboratory in VCA.

Participants

Prof. Jan Plock MD, University of Zurich

PD. Marie-Luce Bochaton-Piallat PhD, University of Geneva

Dr. Pranitha Jayadev Kamat PhD, University of Zurich