Fetoscopic versus Ultrasound-Guided Intravascular Delivery of Maternal Bone Marrow Cells in Fetal Macaques: A Technical Model for Intrauterine Haemopoietic Cell Transplantation.
Fetal Diagn Ther
; 46(3): 175-186, 2019.
Article
en En
| MEDLINE
| ID: mdl-30661073
INTRODUCTION: Significant limitations with existing treatments for major haemoglobinopathies motivate the development of effective intrauterine therapy. We assessed the feasibility of fetoscopic and ultrasound-guided intrauterine haemopoietic cell transplantation (IUHCT) in macaque fetuses in early gestation when haemopoietic and immunological ontogeny is anticipated to enable long-term donor cell engraftment. MATERIAL AND METHODS: Fluorescent-labelled bone marrow-derived mononuclear cells from 10 pregnant Macaca fascicularis were injected into their fetuses at E71-114 (18.9-170.0E+6 cells/fetus) by fetoscopic intravenous (n = 7) or ultrasound (US)-guided intracardiac injections, with sacrifice at 24 h to examine donor-cell distribution. RESULTS: Operating times ranged from 35 to 118 min. Chorionic membrane tenting and intrachorionic haemorrhage were observed only with fetoscopy (n = 2). Labelled cells were stereoscopically visualised in lung, spleen, liver, and placenta. Donor-cell chimerism was highest in liver, spleen, and heart by flow cytometry, placenta by unique polymorphism qPCR, and was undetected in blood. Chimerism was 2-3 log-fold lower in individual organs by qPCR than by flow cytometry. DISCUSSION: Both fetoscopic and US-guided IUHCT were technically feasible, but fetoscopy caused more intraoperative complications in our pilot series. The discrepancy in chimerism detection predicts the challenges in long-term surveillance of donor-cell chimerism. Further studies of long-term outcomes in the non-human primate are valuable for the development of clinical protocols for IUHCT.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ultrasonografía Intervencional
/
Trasplante de Células Madre Hematopoyéticas
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Modelos Animales
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Terapias Fetales
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Fetoscopía
Tipo de estudio:
Guideline
/
Prognostic_studies
/
Qualitative_research
Límite:
Animals
Idioma:
En
Revista:
Fetal Diagn Ther
Asunto de la revista:
DIAGNOSTICO POR IMAGEM
/
OBSTETRICIA
/
PERINATOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Singapur
Pais de publicación:
Suiza