TRANSIENT IMMUNOSUPPRESSION IS EFFECTIVE FOR HUMAN MYOBLAST XENOGRAFT FOR MYOCARDIAL REPAIR
S.J. Jiang1, Kh H.Haider2, L. Ye1, F.L. Chua3, P.K. Law3, J.T. Lu1, E.K.W. Sim1, 1 Department of Cardiothoracic Surgery, National University of Singapore, Singapore-117597, 2 National University Medical Institutes, National University of Singapore, Singapore-117597, 3 Cell Transplantation Inc., Science Park-II, Singapore.
The in vivo behavior of human myoblasts (HM) for heart transplantation remains incompletely characterized. Considering the similarity of porcine and human hearts, we have studied the survival of HM in chronic myocardial ischemia using transient immunosupression.
Human myoblasts were purified from rectus femoris biopsies taken from human donors after their consent. The biopsies were processed by a patented process (Cell Transplant Singapore). The cells were grown on laminin coated flasks, using patented Super medium until confluent. The donor biopsies generated >95% desmin positive HM population with >98% viability. The human myoblasts were transduced with lac-z reporter gene (>75-80% transduction efficiency) for post transplant identification. A Porcine heart model of chronic ischemia in 9 pigs, control group n=3 and cell transplanted group n=6, was created by clamping ameroid ring around left circumflex coronary artery. Four weeks later, twenty injections (0.25ml each) of 5 ml basal medium containing 3x108 cells or without cells were injected into left ventricle wall under direct vision. Immunosupression was achieved with 5mg/kg cyclosporine for six weeks after cell transplantation. Discontinuation of immunosupression after six weeks of cell transplantation showed no signs of donor cell rejection. Animals were euthanized between 6 weeks to 30 weeks after cell transplantation; heart was explanted and processed for histological studies. The results showed lac-z positive donor cells in host cardiac tissue up to 30 weeks post transplantation and expressed human skeletal myosin heavy chain in the pig heart. Immunostaining for proliferative cell nuclear antigen revealed proliferating myoblasts in the host myocardium.
We conclude that HM showed long-term survival in the ischemic cardiac environment using transient immunosupression.
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