The use of human amniotic fluid stem cells as an adjunct to promote pulmonary development in a rabbit model for congenital diaphragmatic hernia

Philip DeKoninck; Jaan Toelen; Xenia Roubliova; Shea Carter; Michela Pozzobon; Francesca Maria Russo; Jute Richter; Pieter-Jan Vandersloten; Erik Verbeken; Paolo De Coppi; Jan Deprest

doi:10.1002/pd.4621

The use of human amniotic fluid stem cells as an adjunct to promote pulmonary development in a rabbit model for congenital diaphragmatic hernia

Philip DeKoninck
, Jaan Toelen
, Xenia Roubliova
, Shea Carter
, Michela Pozzobon
, Francesca Maria Russo
, Jute Richter
, Pieter-Jan Vandersloten
, Erik Verbeken
, Paolo De Coppi
, Jan Deprest^*

^*Corresponding author for this work

Center for Surgical Technologies
Skeletal Biology and Engineering Research Center
University-Teaching Hospital of Padova
University Hospitals Leuven
Great Ormond Street Institute of Child Health
KU Leuven

Research output: Contribution to journal › Article › Academic › peer-review

32 Citations (Scopus)

Abstract

OBJECTIVE: This study aimed to evaluate the potential benefit of intra-tracheal injection of human amniotic fluid stem cells (hAFSC) on pulmonary development combined with TO in a rabbit model for CDH.

METHODS: In time-mated pregnant does a left diaphragmatic defect was created at d23 (term = 31). At d28, previously operated fetuses were assigned to either TO and injection with 70 μL of phosphate buffered saline (PBS) or 1.0 × 10(6) c-Kit positive hAFSC expressing LacZ or were left untouched (CDH). Harvesting was done at d31 to obtain their lung-to-body weight ratio (LBWR), airway and vascular lung morphometry, X-gal staining and immunohistochemistry for Ki67 and surfactant protein-B (SP-B).

RESULTS: CDH-induced pulmonary hypoplasia is countered by TO + PBS, this reverses LBWR, mean terminal bronchiole density (MTBD) and medial thickness to normal. The additional injection of hAFSC decreases MTBD and results in a non-significant decrease in muscularization of intra-acinary vessels. There were no inflammatory changes and LacZ positive hAFSC were dispersed throughout the lung parenchyma 4 days after injection.

CONCLUSION: HAFSC exert an additional effect on TO leading to a decrease in MTBD, a measure of alveolar number surrounding the terminal bronchioles, without signs of toxicity. © 2015 John Wiley & Sons, Ltd.

Original language	English
Pages (from-to)	833-840
Number of pages	8
Journal	Prenatal Diagnosis
Volume	35
Issue number	9
DOIs	https://doi.org/10.1002/pd.4621
Publication status	Published - Sept 2015
Externally published	Yes

Bibliographical note

Funding sources:
PD and JR are beneficiaries of a Marie Curie Industria–Academia Partnership and Pathways grant sponsored by the European Commission
(251356). JDP is beneficiary of a fundamental clinical research grant of the Fonds Wetenschappelijk Onderzoek Vlaanderen (1.801207), and JT from the ‘Klinische
Opleidings- en Onderzoeks- Raad’ of the University Hospitals Leuven. Our experimental program is supported by the Flemish Hercules foundation (large infrastructure
investments AKUL/09/033) and by the KU Leuven (OT/13/115). PDC is supported by the Great Ormond Street Hospital Children’s Charity.
Conflicts of interest: None declared

© 2015 John Wiley & Sons, Ltd.

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10.1002/pd.4621

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DeKoninck, P., Toelen, J., Roubliova, X., Carter, S., Pozzobon, M., Russo, F. M., Richter, J., Vandersloten, P.-J., Verbeken, E., De Coppi, P., & Deprest, J. (2015). The use of human amniotic fluid stem cells as an adjunct to promote pulmonary development in a rabbit model for congenital diaphragmatic hernia. Prenatal Diagnosis, 35(9), 833-840. https://doi.org/10.1002/pd.4621

@article{6933b926a33b4a9ea763129a978258a2,

title = "The use of human amniotic fluid stem cells as an adjunct to promote pulmonary development in a rabbit model for congenital diaphragmatic hernia",

abstract = "OBJECTIVE: This study aimed to evaluate the potential benefit of intra-tracheal injection of human amniotic fluid stem cells (hAFSC) on pulmonary development combined with TO in a rabbit model for CDH.METHODS: In time-mated pregnant does a left diaphragmatic defect was created at d23 (term = 31). At d28, previously operated fetuses were assigned to either TO and injection with 70 μL of phosphate buffered saline (PBS) or 1.0 × 10(6) c-Kit positive hAFSC expressing LacZ or were left untouched (CDH). Harvesting was done at d31 to obtain their lung-to-body weight ratio (LBWR), airway and vascular lung morphometry, X-gal staining and immunohistochemistry for Ki67 and surfactant protein-B (SP-B).RESULTS: CDH-induced pulmonary hypoplasia is countered by TO + PBS, this reverses LBWR, mean terminal bronchiole density (MTBD) and medial thickness to normal. The additional injection of hAFSC decreases MTBD and results in a non-significant decrease in muscularization of intra-acinary vessels. There were no inflammatory changes and LacZ positive hAFSC were dispersed throughout the lung parenchyma 4 days after injection.CONCLUSION: HAFSC exert an additional effect on TO leading to a decrease in MTBD, a measure of alveolar number surrounding the terminal bronchioles, without signs of toxicity. {\textcopyright} 2015 John Wiley \& Sons, Ltd.",

author = "Philip DeKoninck and Jaan Toelen and Xenia Roubliova and Shea Carter and Michela Pozzobon and Russo, \{Francesca Maria\} and Jute Richter and Pieter-Jan Vandersloten and Erik Verbeken and \{De Coppi\}, Paolo and Jan Deprest",

note = "Funding sources: PD and JR are beneficiaries of a Marie Curie Industria–Academia Partnership and Pathways grant sponsored by the European Commission (251356). JDP is beneficiary of a fundamental clinical research grant of the Fonds Wetenschappelijk Onderzoek Vlaanderen (1.801207), and JT from the {\textquoteleft}Klinische Opleidings- en Onderzoeks- Raad{\textquoteright} of the University Hospitals Leuven. Our experimental program is supported by the Flemish Hercules foundation (large infrastructure investments AKUL/09/033) and by the KU Leuven (OT/13/115). PDC is supported by the Great Ormond Street Hospital Children{\textquoteright}s Charity. Conflicts of interest: None declared {\textcopyright} 2015 John Wiley \& Sons, Ltd.",

year = "2015",

month = sep,

doi = "10.1002/pd.4621",

language = "English",

volume = "35",

pages = "833--840",

journal = "Prenatal Diagnosis",

issn = "0197-3851",

publisher = "John Wiley \& Sons Ltd.",

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DeKoninck, P, Toelen, J, Roubliova, X, Carter, S, Pozzobon, M, Russo, FM, Richter, J, Vandersloten, P-J, Verbeken, E, De Coppi, P & Deprest, J 2015, 'The use of human amniotic fluid stem cells as an adjunct to promote pulmonary development in a rabbit model for congenital diaphragmatic hernia', Prenatal Diagnosis, vol. 35, no. 9, pp. 833-840. https://doi.org/10.1002/pd.4621

TY - JOUR

T1 - The use of human amniotic fluid stem cells as an adjunct to promote pulmonary development in a rabbit model for congenital diaphragmatic hernia

AU - DeKoninck, Philip

AU - Toelen, Jaan

AU - Roubliova, Xenia

AU - Carter, Shea

AU - Pozzobon, Michela

AU - Russo, Francesca Maria

AU - Richter, Jute

AU - Vandersloten, Pieter-Jan

AU - Verbeken, Erik

AU - De Coppi, Paolo

AU - Deprest, Jan

N1 - Funding sources: PD and JR are beneficiaries of a Marie Curie Industria–Academia Partnership and Pathways grant sponsored by the European Commission (251356). JDP is beneficiary of a fundamental clinical research grant of the Fonds Wetenschappelijk Onderzoek Vlaanderen (1.801207), and JT from the ‘Klinische Opleidings- en Onderzoeks- Raad’ of the University Hospitals Leuven. Our experimental program is supported by the Flemish Hercules foundation (large infrastructure investments AKUL/09/033) and by the KU Leuven (OT/13/115). PDC is supported by the Great Ormond Street Hospital Children’s Charity. Conflicts of interest: None declared © 2015 John Wiley & Sons, Ltd.

PY - 2015/9

Y1 - 2015/9

N2 - OBJECTIVE: This study aimed to evaluate the potential benefit of intra-tracheal injection of human amniotic fluid stem cells (hAFSC) on pulmonary development combined with TO in a rabbit model for CDH.METHODS: In time-mated pregnant does a left diaphragmatic defect was created at d23 (term = 31). At d28, previously operated fetuses were assigned to either TO and injection with 70 μL of phosphate buffered saline (PBS) or 1.0 × 10(6) c-Kit positive hAFSC expressing LacZ or were left untouched (CDH). Harvesting was done at d31 to obtain their lung-to-body weight ratio (LBWR), airway and vascular lung morphometry, X-gal staining and immunohistochemistry for Ki67 and surfactant protein-B (SP-B).RESULTS: CDH-induced pulmonary hypoplasia is countered by TO + PBS, this reverses LBWR, mean terminal bronchiole density (MTBD) and medial thickness to normal. The additional injection of hAFSC decreases MTBD and results in a non-significant decrease in muscularization of intra-acinary vessels. There were no inflammatory changes and LacZ positive hAFSC were dispersed throughout the lung parenchyma 4 days after injection.CONCLUSION: HAFSC exert an additional effect on TO leading to a decrease in MTBD, a measure of alveolar number surrounding the terminal bronchioles, without signs of toxicity. © 2015 John Wiley & Sons, Ltd.

AB - OBJECTIVE: This study aimed to evaluate the potential benefit of intra-tracheal injection of human amniotic fluid stem cells (hAFSC) on pulmonary development combined with TO in a rabbit model for CDH.METHODS: In time-mated pregnant does a left diaphragmatic defect was created at d23 (term = 31). At d28, previously operated fetuses were assigned to either TO and injection with 70 μL of phosphate buffered saline (PBS) or 1.0 × 10(6) c-Kit positive hAFSC expressing LacZ or were left untouched (CDH). Harvesting was done at d31 to obtain their lung-to-body weight ratio (LBWR), airway and vascular lung morphometry, X-gal staining and immunohistochemistry for Ki67 and surfactant protein-B (SP-B).RESULTS: CDH-induced pulmonary hypoplasia is countered by TO + PBS, this reverses LBWR, mean terminal bronchiole density (MTBD) and medial thickness to normal. The additional injection of hAFSC decreases MTBD and results in a non-significant decrease in muscularization of intra-acinary vessels. There were no inflammatory changes and LacZ positive hAFSC were dispersed throughout the lung parenchyma 4 days after injection.CONCLUSION: HAFSC exert an additional effect on TO leading to a decrease in MTBD, a measure of alveolar number surrounding the terminal bronchioles, without signs of toxicity. © 2015 John Wiley & Sons, Ltd.

U2 - 10.1002/pd.4621

DO - 10.1002/pd.4621

M3 - Article

C2 - 25976324

SN - 0197-3851

VL - 35

SP - 833

EP - 840

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

IS - 9

ER -

The use of human amniotic fluid stem cells as an adjunct to promote pulmonary development in a rabbit model for congenital diaphragmatic hernia

Abstract

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