A proof-of-principle study demonstrates how a cell migration-based selection system can help identify therapeutically significant antibodies. Regenerative medicine relies on the ability to generate specific cell types that can integrate into appropriate sites of function in the body. Richard Lerner and colleagues developed an antibody selection system to identify human antibodies that can induce stem cells to differentiate into cell types that migrate to specific body tissues. In the antibody selection system, the authors infected bone marrow stem cells harvested from mice with a lentivirus-based human antibody library, transplanted the infected stem cells into wild-type mice, and monitored the integration of antibody genes into the genomes of brain cells. Using the approach, the authors identified an antibody named B1, which induced the differentiation of bone marrow stem cells into microglia-like cells; the target of the antibody is a migration-associated cytoskeletal protein called vimentin. The induced microglia-like cells migrated to the brain of mice and exhibited anti-inflammatory properties in in vitro tests. More importantly, in laboratory assays the microglia-like cells phagocytosed the amyloid beta peptide, Aβ1-42, which is implicated in Alzheimer's disease (AD). Adoptive transfer of bone marrow stem cells engineered to carry the gene for the B1 antibody into a mouse model of AD resulted in significant lowering of brain amyloid deposition 6 months after transfer, compared with control mice. The study furnishes proof of principle for the use of cell migration-based selection systems to identify therapeutically significant antibodies, according to the authors.
Article #17-19259: "Migration-based selections of antibodies that convert bone marrow into trafficking microglia-like cells that reduce brain amyloid β," by Kyung Ho Han, Britni Arlian, Matthew Macauley," by Kyung Ho Han, Britni Arlian, Matthew Macauley, Jim Paulson, Richard Alan Lerner
MEDIA CONTACT: Richard Lerner, The Scripps Research Institute, La Jolla, CA; tel: 858-784-8265; e-mail: <firstname.lastname@example.org>