Biomedical subjects

Clark Baumbusch

Publications and source records attributed to Clark Baumbusch.

3 recordsLinked to original sources

PubMed2003

FAK promotes organization of fibronectin matrix and fibrillar adhesions.

Targeted disruption of the focal adhesion kinase (FAK) gene in mice is lethal at embryonic day 8.5 (E8.5). Vascular defects in FAK-/- mice result from the inability of FAK-deficient endothelial cells to organize themselves into vascular network. We found that, although fibronectin (FN) levels were similar, its organization was less fibrillar in both FAK-/- endothelial cells and mesoderm of E8.5 FAK-/- embryos, as well as in mouse embryonic fibroblasts isolated from mutant embryos. FAK catalytic activity, proline-rich domains, and location in focal contacts were all required for proper allocation and patterning of FN matrix. Cells lacking FAK in focal adhesions fail to translocate supramolecular complexes of integrin-bound FN and focal adhesion proteins along actin filaments to form mature fibrillar adhesions. Taken together, our data suggest that proper FN allocation and organization are dependent on FAK-mediated remodeling of focal adhesions.

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PubMed2003

Focal adhesion kinase is required for blood vessel morphogenesis.

The nonreceptor tyrosine kinase focal adhesion kinase (FAK) is a point of convergence for signals from extracellular matrix, soluble factors, and mechanical stimuli. Targeted disruption of the fak gene in mice leads to death at embryonic day 8.5 (E8.5). FAK-/- embryos have severely impaired blood vessel development. Gene expression and in vitro differentiation studies revealed that endothelial cell differentiation was comparable in FAK-/- and wild-type E8.5 embryos. We examined the role of FAK in blood vessel morphogenesis using an in vitro tubulogenesis assay and three different culture systems: FAK+/+ and FAK-/- embryoid bodies, FAK+/+ and FAK-/- endothelial cells, and human umbilical vein endothelial cells expressing antisense FAK, a dominant-negative fragment of FAK, or wild-type FAK. In all of these systems, endothelial cells deficient in FAK expression or function displayed a severely reduced ability to form tubules in Matrigel. These studies demonstrate clearly that the vascular defects in FAK-/- mice result from the inability of FAK-deficient endothelial cells to organize themselves into vascular networks, rather than from defects in tissue-specific differentiation.

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PubMedDate not supplied

Tracing transduced cells in osteochondral defects.

In this study the authors explored the feasibility of using transduced cells for gene therapy to induce healing of osteochondral defects. Both a mouse mesenchymal cell line and mixed rabbit adherent stromal cells were transduced with either liposomal transfection or retroviral transduction using a traceable gene. Transduction efficiency was more than 95% with the retroviral construct and expression was maintained for over 6 months of passage. The liposomal transfection led to a transient expression with an efficiency of 50%. The expression of osteochondral genes was diminished but preserved after transduction in vitro. Transduced rabbit cells were transplanted into osteochondral defects in rabbit femoral condyles. Cells transplanted in vivo could be detected for 4 weeks in the repair tissue. The authors' data demonstrate that mesenchymal cells from bone marrow, stably transduced with a traceable gene product, retain the bone and cartilage phenotype and can be followed in vivo after transplantation into cartilage defects.

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