Postnatal Fate of Donor Mesenchymal Stem Cells after Transamniotic Stem Cell Therapy
*Sarah Tracy1, *Alexander Chalphin1, *Stefanie Lazow1, *Ina Kycia2, *Adam Finkelstein3, *Christopher Chan4, *David Zurakowski2, Dario Fauza2
1Boston Children's Hospital and Beth Israel Deaconess Medical Center, Boston, MA;2Boston Children's Hospital, Boston, MA;3Lafayette College, Easton, PA;4Boston University, Boston, MA
Objective:Donor mesenchymal stem cell (MSC) homing in the fetus after transamniotic stem cell therapy (TRASCET) involves hematogenous routing in the prenatal period. Regulatory feasibility of clinical trials of TRASCET hinges on the postnatal fate of donor MSCs, as potential malignization of cells is a concern. We sought to examine MSC fate after birth in a normal syngeneic model.
Design:After IACUC approval, 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 Lewis rat cells with mesenchymal progenitor identity confirmed by flow cytometry, carrying the reporter gene after lentiviral transduction. Samples from 14 anatomical sites (heart, lung, brain, liver, spleen, pancreas, bowel, kidney, thyroid, skin, skeletal muscle, thymus, peripheral blood and bone marrow) 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 their viability. Statistical analysis was by logistic regression and the Wald test(p<0.05).
Results: Overall survival to P16 was 32%. When controlled by the acellular luciferase injections, donor afMSCs were not identified at any of the anatomical sites, in any neonate, asmeasured 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 neonatal rat pup after concentrated intra-amniotic injection. This finding points to the safety and prospective viability of clinical trials of this novel therapy.
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