First trimester embryo-fetoscopic and ultrasound-guided fetal blood sampling for ex vivo viral transduction of cultured human fetal mesenchymal stem cells.

Chan, Jerry, Kumar, Sailesh and Fisk, Nicholas M. (2008) First trimester embryo-fetoscopic and ultrasound-guided fetal blood sampling for ex vivo viral transduction of cultured human fetal mesenchymal stem cells.. Human Reproduction, 23 11: 2427-2437. doi:10.1093/humrep/den302


Author Chan, Jerry
Kumar, Sailesh
Fisk, Nicholas M.
Title First trimester embryo-fetoscopic and ultrasound-guided fetal blood sampling for ex vivo viral transduction of cultured human fetal mesenchymal stem cells.
Journal name Human Reproduction   Check publisher's open access policy
ISSN 0268-1161
1460-2350
1359-5911
Publication date 2008-11
Sub-type Article (original research)
DOI 10.1093/humrep/den302
Volume 23
Issue 11
Start page 2427
End page 2437
Total pages 11
Place of publication Oxford, U.K.
Publisher Oxford University Press
Collection year 2009
Language eng
Subject C1
111401 Foetal Development and Medicine
920114 Reproductive System and Disorders
1114 Paediatrics and Reproductive Medicine
Formatted abstract
Background: Intrauterine stem cell transplantation is a promising approach for early onset genetic diseases. However, its utility is limited by the development of the fetal immune system after 14 weeks gestation. An ex vivo gene therapy approach targeting autologous first trimester stem cells to replace the missing or defective gene product should overcome this barrier. We investigated the feasibility of harvesting circulating first trimester human fetal mesenchymal stem cells (hfMSCs) for ex vivo gene therapy.
Methods: Thin-gauge embryofetoscopic-directed or ultrasound-guided blood sampling (FBS) was performed in 18 pre-termination fetuses at a mean of 10(+0) (range 7+2 to 13+4) weeks gestation through extra-fetal vessels. Harvested blood was plated for isolation of hfMSC and transduced by lentiviruses.
Results: FBS was successful in 12/18 procedures (67%). Success rates were comparable in fetoscopic (4/6) and ultrasound-guided (8/12) procedures, but procedural time was shorter in the ultrasound-guided arm (P = 0.01). Fetal bradycardia occurred post-FBS in 33% and 25% of fetoscopic and ultrasound cases, respectively, 5 min post-procedure. hfMSCs were isolated in two-thirds of cases, with high efficiency lentiviral transduction achieved without affecting short-term cell renewal.
Conclusions: This phase-one study demonstrates the feasibility of the ex vivo fetal gene therapy approach, in which harvested hfMSCs are genetically manipulated prior to infusion back into the fetus where they should engraft and home to injured tissues. The fetal ex vivo gene therapy paradigm is also of relevance to haemopoietic stem cells to treat inherited haematological diseases. Optimization of stem cell harvest and longer-term safety is required before translation into clinical trials in ongoing pregnancies.
©The Author 2008.
Keyword Fetoscopy
Percutaneous umbilical blood sampling
Fetal blood sampling
Mesenchymal stem cells
Gene therapy
Q-Index Code C1
Q-Index Status Confirmed Code

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 22 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 30 Mar 2009, 17:33:30 EST by Carmen Buttery on behalf of Faculty Of Health Sciences