4.5 Article

Autologous Transplantation of Amniotic Fluid-Derived Mesenchymal Stem Cells Into Sheep Fetuses

Journal

CELL TRANSPLANTATION
Volume 20, Issue 7, Pages 1015-1031

Publisher

COGNIZANT COMMUNICATION CORP
DOI: 10.3727/096368910X543402

Keywords

Autologous stem cell transplantation; Amniotic fluid stem cell; Sheep; In utero

Funding

  1. Chang Gung Memorial Hospital in Taiwan [CMRPG370541, CMRP G370542]
  2. National Science Council of Taiwan [NSC 97-2314-B-182A-057-MY2]
  3. New life foundation for disabled children [UK SG/08-09/10]
  4. Citta della Speranza, Vicenza, Italy
  5. Great Ormond Street Hospital Childrens Charity [V1242, V1230] Funding Source: researchfish

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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 front AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease.

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