Postnatal Fate of Donor Mesenchymal Stem Cells after Transamniotic Stem Cell Therapy
Sarah A. Tracy1,2, Alexander V. Chalphin1,2, Stefanie P. Lazow1,2, Ina Kycia1, Adam Finkelstein1, Christopher Chan3, David Zurakowski1, Dario O. Fauza1
1Boston Children's Hospital, Boston, MA; 2Beth Israel Deaconess Medical Center, Boston, MA; 3Boston University, Boston, MA
Background: Donor mesenchymal stem cell (MSC) trafficking in the fetus after transamniotic stem cell therapy (TRASCET) includes hematogenous routing via the placenta. Feasibility of clinical trials of TRASCET hinges on the postnatal fate of donor MSCs, as potential malignization of cells lingering in the host is a concern. We sought to examine donor MSC fate after birth following TRASCET in a normal syngeneic model.
Methods: Lewis rat fetuses (n=91) were divided into two groups based on the content of volume-matched intra-amniotic injections performed on gestational day 17 (term=21-22 days): either a concentrated suspension of amniotic fluid-derived MSCs (afMSCs) labeled with a luciferase reporter gene (n=38), or an acellular suspension of recombinant luciferase (n=53). Infused afMSCs consisted of syngeneic Lewis rat cells with mesenchymal progenitor identity confirmed by flow cytometry. Samples from 14 anatomical sites from survivors were screened for luciferase activity via microplate luminometry at 16 days of postnatal life (P16). Donor cell presence in available term placentas was also screened to confirm viability. Statistical analysis was by logistic regression and the Wald test (p<0.05).
Results: Overall survival to P16 was 32% (29/91). Donor afMSCs were not identified at any of the anatomical sites, in any neonate, as measured in relative light units (all p>0.05). Donor afMSC presence was confirmed in term placentas.
Conclusions: Donor mesenchymal stem cells are not detectable at any anatomical site in the neonate after intra-amniotic injection in a normal syngeneic rodent model. This finding points to the safety of transamniotic stem cell therapy and to the prospective viability of clinical trials of this novel therapy.
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