Cell Therapy Seen to Ease Blood Loss in Hemophilia A Mouse Model

FVIII is mainly produced by cells known as endothelial cells (ECs), which line the inside of blood vessels. Cell therapy using these cells could be an effective alternative treatment.

Researchers at UC Davis started by creating two lines of induced pluripotent stem cells (iPSCs) derived from two hemophilia A patients. Of note, iPSCs are adult cells that can be reprogrammed back to a stem cell state to generate any type of human cell.

They then differentiated the patient-derived iPSCs into ECs that had been genetically engineered to produce large amounts of FVIII.

Investigators injected the modified ECs into the muscles of neonatal and adult mice that lacked a functional immune system. They found that, in both groups, the transplanted cells survived and grew inside the animals for at least 10 to 16 weeks, leading to the consistent production of FVIII.

Finally, they tested the potential cell therapy in a mouse model of hemophilia A, which lacked a working F8 gene (F8 knock-out mice).

When transplanted into these mice, the modified ECs significantly reduced blood loss — assessed in a bleeding test in which the animals’ tail was clipped — and increased FVIII levels in the blood to between 11.2% and 369.2% of its standard value in humans at two weeks post transplant.

“We also found that the FVIII in the cells functionally corrected or alleviated the animals’ hemophilia A symptoms,” said Ping Zhou, PhD, co-lead investigator of the study.

“As such, we believe that this study is a significant step forward in developing a cell therapy for hemophilia A, and that it provides proof-of concept that [genetically engineered] ECs can serve as an autologous [self] cell factory to deliver FVIII for treating hemophilia A in adults and newborns, too,” Zhou added.