Michael Longaker

Publication Details

  • Donor-derived, liver-specific protein expression after bone marrow transplantation TRANSPLANTATION Jenkins, D. D., Streetz, K., Tataria, M., Sahar, D., Kurobe, M., Longaker, M. T., Kay, M. A., Sylvester, K. G. 2004; 78 (4): 530-536

    Abstract:

    Bone marrow transplantation (BMT) may represent a novel mechanism to deliver a functional gene to a deficient liver. Bone marrow-derived hepatocytes are rare and without a defined contribution to liver function. Consequently, the clinical significance of BMT to treat liver disease is unclear. We sought to quantify bone marrow-derived hepatocyte protein expression after BMT and determine whether the process is inducible with liver injury.Mice transgenic for human alpha-1 antitrypsin (hAAT) under a hepatocyte-specific promoter were used as bone marrow donors. Adenoviral transduction of modified urokinase plasminogen activator (Ad-muPA) was used to induce liver injury. Eight weeks after lethal irradiation and BMT, recipients were stratified into two groups: BMT alone (n = 5) and BMT + Ad-muPA (n= 10). Both groups of animals were bled before (t = 0) and at 2, 4, 8, and 16 weeks after Ad-muPA administration, and the serum samples were assessed for hAAT by enzyme-linked immunosorbent assay.Transgenic donor mice expressed 5 to 10 mg/mL of hAAT. Recipients of BMT alone expressed less than 80 ng/mL of hAAT over all time periods. Animals receiving BMT + Ad-muPA showed sustained and stable hAAT expression of approximately 200 ng/mL. Differences were statistically significant at each time point.Serum protein levels from liver-specific transgene expression are detectable and persist after BMT. Expression is low, but inducible with liver injury. We are currently developing strategies to augment donor-derived, liver-specific protein expression after BMT.

    View details for DOI 10.1097/01.TP.0000130180.42573.BI

    View details for Web of Science ID 000223486500008

    View details for PubMedID 15446311

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