In utero stem cell transplantation and its preliminary application in hemophilia treatment

Objective To explore the feasibility of in utero stem cell transplantation in the treatment of hemophilia.Methods Mononuclear cells derived from RFP transgenic mice's bone marrow were transplanted to each fetus' abdominal cavity by in utero stem cell transplantation technique.The degree of chimerism of RFP cells was examined using RT-PCR after the recipient mice were born.Results For Kun Ming mice group,we transplanted RFP cells into 53 fetuses in utero,and 29 pups were born.The birth rate was 55%.The frequency of chimerism was 79%.The average chimerism rate of a single mouse was 5%,and the highest chimerism rate was 21%.For hemophilia A mice group,we had operations on 21 pregnant mice,and only five of them gave birth and produced 18 pups in total.11 pups were FⅧ deficient,and 8 of them were dead upon or after birth.All of the FⅧ deficient pups' chimerism rates were below 1%,and they bled for more than 10 min without sign of coagulation.Conclusion Our study suggests that it is possible for us to use in utero stem cell transplantation in the treatment of hemophilia.But due to various factors,we have not reach the level of chimerism rate that could cure Hemophilia A.The transplantation process still needs to be optimized.