Highlight
- •Seven clinical studies of fetal liver cell therapy were reported.
- •There were no RCTs, and thus no study was stratified as being of good quality.
- •Logistic limitations of the procedure can be reduced by cryopreservation methods.
- •Preclinical translational studies are necessary to answer relevant clinical questions.
- •Tracing strategies and biopsy-based and solid clinical endpoints are key.
Abstract
The fetal liver is unique because of the coexistence of cells with endodermal and
mesenchymal origins, making it a potential source of hepatic and pancreatic regenerative
medicine. The liver appears at about the third week of gestation, growing rapidly
from the fifth to the 10th week. We define fetal liver from 10 weeks of gestation,
when hematopoietic progenitor cells gradually migrate from the aorta-mesonephros-gonad
region to colonize the liver. Indeed, the fetal liver may be the most available source
of cell therapy for liver disease. We conducted a review of the literature using Medline
and EMBASE (up to May 2021) to identify clinical studies in which patients with liver
disease had been given fetal liver cell therapy. This literature review highlighted
the heterogeneity of cell isolation and selection protocols, which hinders the ability
to pool data and perform a meta-analysis. A limitation of the studies analyzed was
the scarcity of reports (n = 8) and the extremely small sample sizes (median sample
size of treated patients was two), although there was a fairly long follow-up (median
12 months). The weeks after conception ranged from 16 to 34. There were no randomized
controlled trials, and therefore no study was stratified as being of good methodological
quality. Cryopreservation may help to circumvent the critical logistic issues that
hamper the use of fetal liver cell therapy in clinical practice. To help consolidate
the role of the fetal liver in regenerative medicine, good preclinical translational
studies are necessary, whereas tracing strategies and biopsy-based endpoints are crucial
in the clinic, along with well-designed, large, multicenter, randomized controlled
trials using clinically applicable primary outcomes and refined imaging assessment.
Keywords
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Article info
Publication history
Published online: January 24, 2022
Accepted:
October 30,
2021
Received:
June 19,
2021
Identification
Copyright
© 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
