Cargando…
Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair
INTRODUCTION: Fetal myelomeningocele (MMC) repair improves lower extremity motor function. We have previously demonstrated that augmentation of fetal MMC repair with placental mesenchymal stromal cells (PMSCs) seeded on extracellular matrix (PMSC-ECM) further improves motor function in the ovine mod...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372624/ https://www.ncbi.nlm.nih.gov/pubmed/35093254 http://dx.doi.org/10.1016/j.jpedsurg.2021.12.046 |
_version_ | 1785078408649113600 |
---|---|
author | Theodorou, Christina M. Jackson, Jordan E. Stokes, Sarah C. Pivetti, Christopher D. Kumar, Priyadarsini Paxton, Zachary J. Matsukuma, Karen E. Yamashiro, Kaeli J. Reynaga, Lizette Hyllen, Alicia A. de Lorimier, Arthur J. Hassan, Maheen Wang, Aijun Farmer, Diana L. Saadai, Payam |
author_facet | Theodorou, Christina M. Jackson, Jordan E. Stokes, Sarah C. Pivetti, Christopher D. Kumar, Priyadarsini Paxton, Zachary J. Matsukuma, Karen E. Yamashiro, Kaeli J. Reynaga, Lizette Hyllen, Alicia A. de Lorimier, Arthur J. Hassan, Maheen Wang, Aijun Farmer, Diana L. Saadai, Payam |
author_sort | Theodorou, Christina M. |
collection | PubMed |
description | INTRODUCTION: Fetal myelomeningocele (MMC) repair improves lower extremity motor function. We have previously demonstrated that augmentation of fetal MMC repair with placental mesenchymal stromal cells (PMSCs) seeded on extracellular matrix (PMSC-ECM) further improves motor function in the ovine model. However, little progress has been made in improving bowel and bladder function, with many patients suffering from neurogenic bowel and bladder. We hypothesized that fetal MMC repair with PMSC-ECM would also improve bowel and bladder function. METHODS: MMC defects were surgically created in twelve ovine fetuses at median gestational age (GA) 73 days, followed by defect repair at GA101 with PMSC-ECM. Fetuses were delivered at GA141. Primary bladder function outcomes were voiding posture and void volumes. Primary bowel function outcome was anorectal manometry findings including resting anal pressure and presence of rectoanal inhibitory reflex (RAIR). Secondary outcomes were anorectal and bladder detrusor muscle thickness. PMSC-ECM lambs were compared to normal lambs (n = 3). RESULTS: Eighty percent of PMSC-ECM lambs displayed normal voiding posture compared to 100% of normal lambs (p = 1). Void volumes were similar (PMSC-ECM 6.1 ml/kg vs. normal 8.8 ml/kg, p = 0.4). Resting mean anal pressures were similar between cohorts (27.0 mmHg PMSC-ECM vs. normal 23.5 mmHg, p = 0.57). RAIR was present in 3/5 PMSC-ECM lambs that underwent anorectal manometry and all normal lambs (p = 0.46). Thicknesses of anal sphincter complex, rectal wall muscles, and bladder detrusor muscles were similar between cohorts. CONCLUSION: Ovine fetal MMC repair augmented with PMSC-ECM results in near-normal bowel and bladder function. Further work is needed to evaluate these outcomes in human patients. |
format | Online Article Text |
id | pubmed-10372624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-103726242023-07-27 Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair Theodorou, Christina M. Jackson, Jordan E. Stokes, Sarah C. Pivetti, Christopher D. Kumar, Priyadarsini Paxton, Zachary J. Matsukuma, Karen E. Yamashiro, Kaeli J. Reynaga, Lizette Hyllen, Alicia A. de Lorimier, Arthur J. Hassan, Maheen Wang, Aijun Farmer, Diana L. Saadai, Payam J Pediatr Surg Article INTRODUCTION: Fetal myelomeningocele (MMC) repair improves lower extremity motor function. We have previously demonstrated that augmentation of fetal MMC repair with placental mesenchymal stromal cells (PMSCs) seeded on extracellular matrix (PMSC-ECM) further improves motor function in the ovine model. However, little progress has been made in improving bowel and bladder function, with many patients suffering from neurogenic bowel and bladder. We hypothesized that fetal MMC repair with PMSC-ECM would also improve bowel and bladder function. METHODS: MMC defects were surgically created in twelve ovine fetuses at median gestational age (GA) 73 days, followed by defect repair at GA101 with PMSC-ECM. Fetuses were delivered at GA141. Primary bladder function outcomes were voiding posture and void volumes. Primary bowel function outcome was anorectal manometry findings including resting anal pressure and presence of rectoanal inhibitory reflex (RAIR). Secondary outcomes were anorectal and bladder detrusor muscle thickness. PMSC-ECM lambs were compared to normal lambs (n = 3). RESULTS: Eighty percent of PMSC-ECM lambs displayed normal voiding posture compared to 100% of normal lambs (p = 1). Void volumes were similar (PMSC-ECM 6.1 ml/kg vs. normal 8.8 ml/kg, p = 0.4). Resting mean anal pressures were similar between cohorts (27.0 mmHg PMSC-ECM vs. normal 23.5 mmHg, p = 0.57). RAIR was present in 3/5 PMSC-ECM lambs that underwent anorectal manometry and all normal lambs (p = 0.46). Thicknesses of anal sphincter complex, rectal wall muscles, and bladder detrusor muscles were similar between cohorts. CONCLUSION: Ovine fetal MMC repair augmented with PMSC-ECM results in near-normal bowel and bladder function. Further work is needed to evaluate these outcomes in human patients. 2022-05 2022-01-13 /pmc/articles/PMC10372624/ /pubmed/35093254 http://dx.doi.org/10.1016/j.jpedsurg.2021.12.046 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ) |
spellingShingle | Article Theodorou, Christina M. Jackson, Jordan E. Stokes, Sarah C. Pivetti, Christopher D. Kumar, Priyadarsini Paxton, Zachary J. Matsukuma, Karen E. Yamashiro, Kaeli J. Reynaga, Lizette Hyllen, Alicia A. de Lorimier, Arthur J. Hassan, Maheen Wang, Aijun Farmer, Diana L. Saadai, Payam Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair |
title | Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair |
title_full | Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair |
title_fullStr | Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair |
title_full_unstemmed | Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair |
title_short | Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair |
title_sort | early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372624/ https://www.ncbi.nlm.nih.gov/pubmed/35093254 http://dx.doi.org/10.1016/j.jpedsurg.2021.12.046 |
work_keys_str_mv | AT theodorouchristinam earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT jacksonjordane earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT stokessarahc earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT pivettichristopherd earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT kumarpriyadarsini earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT paxtonzacharyj earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT matsukumakarene earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT yamashirokaelij earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT reynagalizette earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT hyllenaliciaa earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT delorimierarthurj earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT hassanmaheen earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT wangaijun earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT farmerdianal earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair AT saadaipayam earlyinvestigationsintoimprovingbowelandbladderfunctioninfetalovinemyelomeningocelerepair |