Ultrasound-guided in Utero Transplantation of Placental Stem Cells into the Liver of Crigler-Najjar Syndrome Model Rat.
Animals
Cell Survival
Crigler-Najjar Syndrome
/ diagnostic imaging
Disease Models, Animal
Female
Fetal Therapies
/ adverse effects
Gestational Age
Graft Survival
Humans
Liver
/ diagnostic imaging
Placenta
/ cytology
Pregnancy
Rats, Gunn
Stem Cell Transplantation
/ adverse effects
Time Factors
Transplantation, Heterologous
Ultrasonography, Interventional
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
pubmed:
16
4
2019
medline:
2
6
2020
entrez:
16
4
2019
Statut:
ppublish
Résumé
Advances in prenatal screening and early diagnosis of genetic disease will potentially allow for preemptive treatment of anticipated postnatal disease by in utero cell transplantation (IUCT). This strategy carries potential benefits over postnatal treatment, which might allow for improved engraftment and function of the transplanted cells. Congenital metabolic disorders may be an ideal target for this type of therapy, as in most cases, they require replacement of a single deficient hepatic enzyme, and multiple small-animal models exist for preclinical testing. The Gunn rat, a Crigler-Najjar syndrome model animal lacking UDP-glucuronosyltransferase (UGT1A1), was used as recipient. Human amniotic epithelial cells (hAECs), which possess hepatic differentiation potential, were transplanted into the midgestation fetal Gunn rat liver via ultrasound-guided IUCT. The impact of IUCT on live birth and postnatal survival was evaluated. Human cell engraftment was immunohistochemically analyzed on postnatal day 21. Ultrasound-guided IUCT was conducted in rat fetuses on embryonic day 16. Following IUCT, the antihuman mitochondria-positive cells were detected in the liver of recipient rats at postnatal day 21. Here, we have introduced ultrasound-guided IUCT of hAEC using a small-animal model of a congenital metabolic disorder without immunosuppression. The immunological advantage of IUCT was demonstrated with xenogeneic IUCT. This procedure is suitable to conduct preclinical studies for exploring the feasibility and efficacy of ultrasound-guided transuterine cell injection using rodent disease models.
Sections du résumé
BACKGROUND
Advances in prenatal screening and early diagnosis of genetic disease will potentially allow for preemptive treatment of anticipated postnatal disease by in utero cell transplantation (IUCT). This strategy carries potential benefits over postnatal treatment, which might allow for improved engraftment and function of the transplanted cells. Congenital metabolic disorders may be an ideal target for this type of therapy, as in most cases, they require replacement of a single deficient hepatic enzyme, and multiple small-animal models exist for preclinical testing.
METHODS
The Gunn rat, a Crigler-Najjar syndrome model animal lacking UDP-glucuronosyltransferase (UGT1A1), was used as recipient. Human amniotic epithelial cells (hAECs), which possess hepatic differentiation potential, were transplanted into the midgestation fetal Gunn rat liver via ultrasound-guided IUCT. The impact of IUCT on live birth and postnatal survival was evaluated. Human cell engraftment was immunohistochemically analyzed on postnatal day 21.
RESULTS
Ultrasound-guided IUCT was conducted in rat fetuses on embryonic day 16. Following IUCT, the antihuman mitochondria-positive cells were detected in the liver of recipient rats at postnatal day 21.
CONCLUSIONS
Here, we have introduced ultrasound-guided IUCT of hAEC using a small-animal model of a congenital metabolic disorder without immunosuppression. The immunological advantage of IUCT was demonstrated with xenogeneic IUCT. This procedure is suitable to conduct preclinical studies for exploring the feasibility and efficacy of ultrasound-guided transuterine cell injection using rodent disease models.
Identifiants
pubmed: 30985583
doi: 10.1097/TP.0000000000002735
pmc: PMC6594893
mid: NIHMS1525550
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e182-e187Subventions
Organisme : NIDDK NIH HHS
ID : R25 DK078385
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR023653
Pays : United States
Organisme : NIH HHS
ID : S10 OD018096
Pays : United States
Commentaires et corrections
Type : CommentIn
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