Gene Therapy with Transplanted Cells Shows Promise in Hemophilia A Mice

Researchers from the University of California (UC), Davis have been investigating whether two genetically engineered cell types could be customized for long term therapeutic benefit in individuals with hemophilia A. To this end, Aijun Wang, PhD co-director of the surgical bioengineering laboratory at UC Davis and his team treated hemophilia A mice subjects with this unique gene therapy.

Through an intramuscular injection, the mice subjects received human-sourced endothelial colony-forming cells (ECFCs) and placenta-derived mesenchymal stromal cells (PMSCs). ECFCs can multiply and take on the characteristics of endothelial cells, which typically line the walls of blood vessels in organs such as the heart, liver and intestines and are known to produce FVIII. PMSCs are, according to the authors, “well established as a stem cell therapy product for a wide variety of diseases and conditions.” 

The ECFCs and PMSCs were specifically engineered with a version of the FVIII gene, along with repurposed retroviruses called lentiviral vectors. These vectors act as vehicles, carrying the customized genetic material to elicit the production of FVIII. One advantage in using lentiviruses is that most patients do not generate antibodies to this type of vector, avoiding an immune response that would otherwise render the treatment ineffective. Another benefit of using lentiviral vectors is their large size, enabling them to deliver greater concentrations of the FVIII gene to produce a more optimal therapeutic effect.

While a drawback to using transplanted cells can be a very brief period of viability – in this case only short-term FVIII production – the outcomes here were promising. The results showed that the co-transplant of PMSCs and ECFCs resulted in the most optimal and enduring transplants, yielding a functional FVIII inside the mice’s bodies over at least six months. Investigators also observed that the more successful transplants were performed a few days after birth, versus those performed in adult mice. Following therapy, neonatal hemophilia A mouse models with less than 1% of FVIII saw a two-thirds reduction in blood loss in response to a cut.

“This work demonstrated that co-transplantation of ECFCs with PMSCs at the neonatal age is a potential strategy to achieve stable, long-term engraftment, and thus holds great promise for cell-based treatment of hemophilia A,” concluded the authors.

The study, “Potential Long-Term Treatment of Hemophilia A by Neonatal Co-Transplantation of Cord Blood-Derived Endothelial Colony-Forming Cells and Placental Mesenchymal Stromal Cells,” was published in the journal Stem Cell Research & Therapy.

Source: Hemophilia News Today, January 28, 2019