Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into sheep fetuses
Authors: Sveva Bollini
Elisa Filppi
Anna L David
Vedanta Mehta
S W Steven Shaw
Paolo De Coppi
Mara Cananzi
H Bobby Gaspar
Khalil Abi Nader
Annalisa Gastaldello
Waseem Qasim
Journal: Cell Transplantation (2011)
Discipline: CLINICAL MEDICINE
Keywords: Long-term engraftment; phenotype correction; in utero stem cell transplantation; allogeneic rejection; amniotic fluid
Affiliations: Prenatal Cell and Gene Therapy Group, Institute for Women’s Health, University College London, London, UK.

Abstract:  Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-guided amniocentesis in early gestation pregnant sheep (n = 9, 58 days of gestation, term = 145 days). AFMSCs were isolated and expanded in all sampled fetal sheep. Those cells were transduced using an HIV vector encoding enhanced green fluorescent protein (GFP) with 63.2% (range 38.3-96.2%) transduction efficiency rate. After expansion, transduced AFMSCs were injected into the peritoneal cavity of each donor fetal sheep at 76 days under ultrasound guidance. One ewe miscarried twin fetuses after amniocentesis. Intraperitoneal injection was successful in the remaining 7 fetal sheep giving a 78% survival for the full procedure. Tissues were sampled at postmortem examination 2 weeks later. PCR analysis detected GFP-positive cells in fetal tissues including liver, heart, placenta, membrane, umbilical cord, adrenal gland, and muscle. GFP protein was detected in these tissues by Western blotting and further confirmed by cytofluorimetric and immunofluorescence analyses. This is the first demonstration of autologous stem cell transplantation in the fetus using AFMSCs. Autologous cells derived from AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease. 

Retracted: No

PubPeer comments:
 This paper has a 2016 correction for a misspelled author name, found here: https: journals.sagepub.com doi pdf 10.3727 096368916X691006 Could the authors please also check Figure 8? * Yellow boxes: the DAPI (and Merge) panels of the AFMSCs in Figure 8a appear to overlap with the DAPI and Merge panels of the Injected Fetal Liver row in Figure 8b. Are these showing the same sample? ![file] , 
 Dear Professor Bik Thank you for your comment on our paper. We are investigating your findings and will come back to you shortly. Yours sincerely Anna David on behalf of first author Dr Steven Shaw, and co-last author Prof Paolo de Coppi , 
 Dear Dr. David et al. It s been almost a year. Any update that is worth sharing here? , 
 Dear Professor Bik Thank your for pointing out this Figure to us. We have investigated it and found one mistake in Figure 8 whereby the DAPI (and Merge) panels of the AFMSCs in Figure 8a are images of the same samples as a zoomed DAPI and Merge panels of the Injected Fetal Liver row in Figure 8b, as you pointed out. We have rechecked our experimental data from the original files and agree that there is an error in that we accidentally chose the incorrect original images for the AFMSC row and did not appreciate the duplication. We sincerely apologise for this mistake and thank you for alerting us to it. We have identified the correct images for the DAPI (and Merge) panels of the AFMSCs row in Figure 8a and have created an amended Figure 8. I wrote to the journal publishers in November 2021 requesting that the scientific record be amended - I have again contacted them this week as I have not yet had a response. I will post again once I hear back from them about correcting the manuscript. Yours sincerely Anna David on behalf of first author Dr Steven Shaw, and co-last author Prof Paolo de Coppi , 
 Dear Professor Bik. The corrigendum article is now published in Cell Transplantation. Yours sincerely Anna David on behalf of first author Dr Steven Shaw, and co-last author Prof Paolo de Coppi. Corrigendum to: Shaw SWS, Bollini S, Nader KA, et al. Autologous Transplantation of Amniotic Fluid-Derived Mesenchymal Stem Cells into Sheep Fetuses. Cell Transplantation. March 2016:615-615. doi:10.3727 096368916X691006![file] https: journals.sagepub.com doi full 10.1177 09636897221112705 ,