Mesenchymal stem cells as vehicles for gene delivery

J. D. Mosca, J. K. Hendricks, D. Buyaner, J. Davis-Sproul, L. C. Chuang, M. K. Majumdar, R. Chopra, F. Barry, M. Murphy, M. A. Thiede, U. Junker, R. J. Rigg, S. P. Forestell, E. Bohnlein, R. Storb, B. M. Sandmaier

Research output: Contribution to journalArticle

Abstract

Mesenchymal stem cells contribute to the regeneration of mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, adipose, and marrow stroma. Transduction of mesenchymal stem cells from species other than humans is required for the development of disease models in which mesenchymal stern cells-based gene delivery is evaluated. Attempts to transduce mesenchymal stem cells from some species with amphotropic retroviral vectors were unsuccessful, leading to comparative mesenchymal stem cells transductions with xenotroplc and gibbon-ape leukemia virus envelope-pseudotyped retroviral vectors. Human, baboon, canine, and rat mesenchymal stem cells were transduced optimally with amphotropic vector supernatants. In contrash, sheep, goat, and pig mesenchymal stem cells showed highest transduction levels with xenotropic retroviral vector supernatant, and rabbit mesenchymal stem cells were transduced optimally with gibbon-ape-enveloped vectors. Using a myeloablative canine transplantation model and gene-marked canine mesenchymal stem cells, the biodistribution of infused and ex vivo expanded mesenchymal stem cells were examined. The majority of transduced canine mesenchymal stem cells were found in the bone marrow samples. The current study shows the use of mesenchymal stem cells as a delivery vehicle for gene transfer studies, and validates the feasibility of delivering mesenchymal stem cells to the marrow compartment for stromal regeneration after cancer-associated cytotoxic therapies.

Original languageEnglish (US)
Pages (from-to)S71-S90
JournalClinical orthopaedics and related research
Issue number379 SUPPL.
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

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  • Cite this

    Mosca, J. D., Hendricks, J. K., Buyaner, D., Davis-Sproul, J., Chuang, L. C., Majumdar, M. K., Chopra, R., Barry, F., Murphy, M., Thiede, M. A., Junker, U., Rigg, R. J., Forestell, S. P., Bohnlein, E., Storb, R., & Sandmaier, B. M. (2000). Mesenchymal stem cells as vehicles for gene delivery. Clinical orthopaedics and related research, (379 SUPPL.), S71-S90. https://doi.org/10.1097/00003086-200010001-00011