Linked Life Data

9472777

Source:http://linkedlifedata.com/resource/pubmed/id/9472777

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-3-25
pubmed:abstractText
Murine retroviral vectors have the potential to mediate stable gene transfer into hematopoietic progenitor cells. A known drawback to the use of these vectors is that transduction can only take place in cells actively progressing through the cell cycle. Thrombopoietin, the c-mpl ligand, is known to support division of hematopoietic precursors of primitive origin. Polyethylene glycol (PEG)-conjugated recombinant human megakaryocyte growth and development factor (MGDF) is a polypeptide related to thrombopoietin that stimulates megakaryocyte production. To investigate whether MGDF would also induce stem cell division and support retroviral transduction of CD34+ cells, we compared the effects of MGDF, stem cell factor (SCF), interleukin-3 (IL-3), and IL-6, alone or in combination, using amphotropic and vesicular stomatitis virus (VSV-G) pseudotyped murine retroviral vectors. Similar transduction efficiency was observed when CD34+ cells were transduced in the presence of SCF and MGDF as compared to SCF, IL-3, and IL-6. Using the SCID-hu mouse model of thymopoiesis, we investigated whether CD34+ cells transduced in the presence of these cytokines could reconstitute irradiated thymic implants, and whether vector sequences were present in mature thymocytes. At early timepoints, no significant differences were observed on engraftment of donor progenitors incubated with each cytokine combination. However, a significant difference in the percentage of donor derived CD4+/CD8+ immature thymocytes was observed 9 weeks after implantation of CD34+ cells exposed to the combination of SCF and MGDF as compared to SCF, IL-3, and IL-6 (p = 0.04), indicating that MGDF/SCF better supported the survival of thymocyte precursor cells. Approximately 4% of thymocytes in both cytokine groups harbored vector sequences. These studies provide evidence that MGDF and SCF in combination can mediate transduction of hematopoietic progenitors capable of contributing to long-term thymopoiesis. These results may have important applications for the implementation of gene therapy strategies in disorders affecting the T lymphoid system.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-83
pubmed:dateRevised
2011-9-7
pubmed:meshHeading
pubmed-meshheading:9472777-Animals, pubmed-meshheading:9472777-Antigens, CD, pubmed-meshheading:9472777-Antigens, CD43, pubmed-meshheading:9472777-Bone Marrow Cells, pubmed-meshheading:9472777-Cell Survival, pubmed-meshheading:9472777-Cells, Cultured, pubmed-meshheading:9472777-Cytokines, pubmed-meshheading:9472777-Humans, pubmed-meshheading:9472777-Immunophenotyping, pubmed-meshheading:9472777-Mice, pubmed-meshheading:9472777-Mice, SCID, pubmed-meshheading:9472777-Polyethylene Glycols, pubmed-meshheading:9472777-Recombinant Proteins, pubmed-meshheading:9472777-Retroviridae, pubmed-meshheading:9472777-Sialoglycoproteins, pubmed-meshheading:9472777-Stem Cells, pubmed-meshheading:9472777-T-Lymphocyte Subsets, pubmed-meshheading:9472777-Thrombopoietin, pubmed-meshheading:9472777-Transduction, Genetic
pubmed:year
1998
pubmed:articleTitle
Effects of megakaryocyte growth and development factor on survival and retroviral transduction of T lymphoid progenitor cells.
pubmed:affiliation
Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095-1678, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't