Faculty Research 1990 - 1999
LacZ and interleukin-3 expression in vivo after retroviral transduction of marrow-derived human osteogenic mesenchymal progenitors.
Document Type
Article
Publication Date
1997
Keywords
Adult, Animal, Bone-and-Bones: cy, ph, Bone-Marrow: cy, Cell-Differentiation, Cell-Transplantation: mt, Cells-Cultured, Ceramics, Gene-Expression-Regulation, Human, Interleukin-3: ge, me, Mesoderm: cy, Mice, Mice-SCID, Recombinant-Proteins: ge, me, Retroviridae: ge, Stem-Cells, SUPPORT-U-S-GOVT-P-H-S, Transduction-Genetic
First Page
1417
Last Page
1427
JAX Source
Hum Gene Ther 1997 Aug 10;8(12):1417-27
Grant
P30CA43703/CA/NCI, P30CA63193/CA/NCI, P30ES06288/ES/NIEHS
Abstract
Human marrow-derived mesenchymal progenitor cells (hMPCs), which have the capacity for osteogenic and marrow stromal differentiation, were transduced with the myeloproliferative sarcoma virus (MPSV)-based retrovirus, vM5LacZ, that contains the LacZ and neo genes. Stable transduction and gene expression occurred in 18% of cells. After culture expansion and selection in G418, approximately 70% of neo(r) hMPCs co-expressed LacZ. G418-selected hMPC retain their osteogenic potential and form bone in vivo when seeded into porous calcium phosphate ceramic cubes implanted subcutaneously into SCID mice. LacZ expression was evident within osteoblasts and osteocytes in bone developing within the ceramics 6 and 9 weeks after implantation. Likewise, hMPCs transduced with human interleukin-3 (hIL-3) cDNA, adhered to ceramic cubes and implanted into SCID mice, formed bone and secreted detectable levels of hIL-3 into the systemic circulation for at least 12 weeks. These data indicate that genetically transduced, culture-expanded bone marrow-derived hMPCs retain a precursor phenotype and maintain similar levels of transgene expression during osteogenic lineage commitment and differentiation in vivo. Because MPCs have been shown to differentiate into bone, cartilage, and tendon, these cells may be a useful target for gene therapy.
Recommended Citation
Allay JA,
Dennis JE,
Haynesworth SE,
Majumdar MK,
Clapp DW,
Shultz LD,
Caplan AI,
Gerson SL.
LacZ and interleukin-3 expression in vivo after retroviral transduction of marrow-derived human osteogenic mesenchymal progenitors. Hum Gene Ther 1997 Aug 10;8(12):1417-27