Researchers discovered that certain types of a patient’s own cells were viable candidates for delivering a long-lasting factor VIII transgene to treat hemophilia A, according to a news release on a study published in the Frontiers in Cell and Developmental Biology. The cell types investigated were mesenchymal stromal cells from amniotic fluid, the umbilical cord, and bone marrow.
Hemophilia A is an X-linked coagulopathy usually treated with factor VIII products a few times a week. The problem with that treatment framework is that the factor VIII products are expensive and unavailable to approximately 75% of patients with this condition, the authors said.
Moreover, the current treatment cannot guarantee lifelong disease management, as some patients develop inhibitors that cause the treatment to be ineffective. Researchers from the Wake Forest Institute for Regenerative Medicine (WFIRM) in Winston-Salem, North Carolina therefore decided to investigate if it was feasible to use autologous cells for the delivery of long-lasting factor VIII protein to treat hemophilia A.
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Their study included the use of amniotic fluid-derived, neonatal, and adult cells, which according to the news release is “the first in-depth analysis of any of these cell types for their use to deliver the [factor] VIII protein.”
Researchers compared mesenchymal stromal cells from amniotic fluid, umbilical cord, and bone marrow. They were all found to be viable candidates as cellular vehicles for the delivery of factor VIII. However, they found that there were significant differences in the amount of factor VIII produced by similar cell types isolated from different tissues.
Researchers discovered that cells derived from umbilical cord tissue yielded the highest amounts of factor VIII mRNA and blood clotting activity (after transduction with a vector encoding a B domain-deleted human F8 transgene). The levels of factor VIII synthesis exceeded that of the human hepatic sinusoidal endothelial cells, which was believed to be the body’s main site for factor VIII synthesis.
Cell therapy in the field of hemophilia research offers exciting new therapeutic possibilities. As mentioned by co-author and WFIRM Director Anthony Atala, MD, “The goal of this work is to be able to provide a long-lasting and curative treatment option for patients with hemophilia A by using their own cells. We look forward to seeing this work progress.”
Promising autologous cell candidates identified as potential delivery vehicles for Hemophilia A treatment. News release. Wake Forest Institute for Regenerative Medicine; September 17, 2021.
Stem C, Rodman C, Ramamurthy RM, et al. Investigating optimal autologous cellular platforms for prenatal or perinatal factor VIII delivery to treat hemophilia A. Front Cell Dev Biol. Published online August 10, 2021. doi:10.3389/fcell.2021.678117