Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair
•Myelomeningocele is associated with significant bowel and bladder dysfunction.•Fetal ovine myelomeningocele repair augmented with placental mesenchymal stem cells was associated with near-normal bowel and bladder function. Fetal myelomeningocele (MMC) repair improves lower extremity motor function....
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| Veröffentlicht in: | Journal of pediatric surgery 2022-05, Vol.57 (5), p.941-948 |
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| creator | 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 |
| description | •Myelomeningocele is associated with significant bowel and bladder dysfunction.•Fetal ovine myelomeningocele repair augmented with placental mesenchymal stem cells was associated with near-normal bowel and bladder function.
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.
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).
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.
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. |
| doi_str_mv | 10.1016/j.jpedsurg.2021.12.046 |
| format | Article |
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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.
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).
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.
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.</description><identifier>ISSN: 0022-3468</identifier><identifier>EISSN: 1531-5037</identifier><identifier>DOI: 10.1016/j.jpedsurg.2021.12.046</identifier><identifier>PMID: 35093254</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Bladder function ; Bowel function ; Cellular therapy ; Female ; Fetal surgery ; Fetus - surgery ; Humans ; Meningomyelocele - complications ; Meningomyelocele - surgery ; Mesenchymal Stem Cells ; Myelomeningocele ; Placenta ; Pregnancy ; Sheep ; Sheep, Domestic ; Spina bifida ; Urinary Bladder - surgery</subject><ispartof>Journal of pediatric surgery, 2022-05, Vol.57 (5), p.941-948</ispartof><rights>2022</rights><rights>Copyright © 2022. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-bda0c74556c36f998ec7886057cdaa43a1b0169e186d8d4f17f778362812518a3</citedby><cites>FETCH-LOGICAL-c472t-bda0c74556c36f998ec7886057cdaa43a1b0169e186d8d4f17f778362812518a3</cites><orcidid>0000-0002-0365-3053</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022346822000276$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35093254$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Theodorou, Christina M.</creatorcontrib><creatorcontrib>Jackson, Jordan E.</creatorcontrib><creatorcontrib>Stokes, Sarah C.</creatorcontrib><creatorcontrib>Pivetti, Christopher D.</creatorcontrib><creatorcontrib>Kumar, Priyadarsini</creatorcontrib><creatorcontrib>Paxton, Zachary J.</creatorcontrib><creatorcontrib>Matsukuma, Karen E.</creatorcontrib><creatorcontrib>Yamashiro, Kaeli J.</creatorcontrib><creatorcontrib>Reynaga, Lizette</creatorcontrib><creatorcontrib>Hyllen, Alicia A.</creatorcontrib><creatorcontrib>de Lorimier, Arthur J.</creatorcontrib><creatorcontrib>Hassan, Maheen</creatorcontrib><creatorcontrib>Wang, Aijun</creatorcontrib><creatorcontrib>Farmer, Diana L.</creatorcontrib><creatorcontrib>Saadai, Payam</creatorcontrib><title>Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair</title><title>Journal of pediatric surgery</title><addtitle>J Pediatr Surg</addtitle><description>•Myelomeningocele is associated with significant bowel and bladder dysfunction.•Fetal ovine myelomeningocele repair augmented with placental mesenchymal stem cells was associated with near-normal bowel and bladder function.
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.
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).
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.
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.</description><subject>Animals</subject><subject>Bladder function</subject><subject>Bowel function</subject><subject>Cellular therapy</subject><subject>Female</subject><subject>Fetal surgery</subject><subject>Fetus - surgery</subject><subject>Humans</subject><subject>Meningomyelocele - complications</subject><subject>Meningomyelocele - surgery</subject><subject>Mesenchymal Stem Cells</subject><subject>Myelomeningocele</subject><subject>Placenta</subject><subject>Pregnancy</subject><subject>Sheep</subject><subject>Sheep, Domestic</subject><subject>Spina bifida</subject><subject>Urinary Bladder - surgery</subject><issn>0022-3468</issn><issn>1531-5037</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u3CAUhVHVqpkmeYWIZTd2ARuMV20VpUmlSN20a4ThesoIgwv2VPP2xZokalddIeA79-cchG4oqSmh4sOhPsxg85r2NSOM1pTVpBWv0I7yhlacNN1rtCOEsapphbxA73I-EFKeCX2LLhpO-obxdofgTid_wi4cIS9urxcXQy7XJWI3zSkeXdjjIf4Gj3WwePDaWkh4XIPZ0ELiERbt8UYCnk7g4wShqKIBDzjBrF26Qm9G7TNcP52X6MeXu--3D9Xjt_uvt58fK9N2bKkGq4npWs6FacTY9xJMJ6UgvDNW67bRdCi790ClsNK2I-3GrpONYJIyTqVuLtHHc915HSawBsKStFdzcpNOJxW1U__-BPdT7eNR0eIME6wtFd4_VUjx11o8UZPLZROvA8Q1qw2iPSdcFlScUZNizgnGlz6UqC0kdVDPIaktJEWZKiEV4c3fU77InlMpwKczAMWro4OksnEQDFiXwCzKRve_Hn8A6hOpcw</recordid><startdate>20220501</startdate><enddate>20220501</enddate><creator>Theodorou, Christina M.</creator><creator>Jackson, Jordan E.</creator><creator>Stokes, Sarah C.</creator><creator>Pivetti, Christopher D.</creator><creator>Kumar, Priyadarsini</creator><creator>Paxton, Zachary J.</creator><creator>Matsukuma, Karen E.</creator><creator>Yamashiro, Kaeli J.</creator><creator>Reynaga, Lizette</creator><creator>Hyllen, Alicia A.</creator><creator>de Lorimier, Arthur J.</creator><creator>Hassan, Maheen</creator><creator>Wang, Aijun</creator><creator>Farmer, Diana L.</creator><creator>Saadai, Payam</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0365-3053</orcidid></search><sort><creationdate>20220501</creationdate><title>Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-bda0c74556c36f998ec7886057cdaa43a1b0169e186d8d4f17f778362812518a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Bladder function</topic><topic>Bowel function</topic><topic>Cellular therapy</topic><topic>Female</topic><topic>Fetal surgery</topic><topic>Fetus - surgery</topic><topic>Humans</topic><topic>Meningomyelocele - complications</topic><topic>Meningomyelocele - surgery</topic><topic>Mesenchymal Stem Cells</topic><topic>Myelomeningocele</topic><topic>Placenta</topic><topic>Pregnancy</topic><topic>Sheep</topic><topic>Sheep, Domestic</topic><topic>Spina bifida</topic><topic>Urinary Bladder - surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Theodorou, Christina M.</creatorcontrib><creatorcontrib>Jackson, Jordan E.</creatorcontrib><creatorcontrib>Stokes, Sarah C.</creatorcontrib><creatorcontrib>Pivetti, Christopher D.</creatorcontrib><creatorcontrib>Kumar, Priyadarsini</creatorcontrib><creatorcontrib>Paxton, Zachary J.</creatorcontrib><creatorcontrib>Matsukuma, Karen E.</creatorcontrib><creatorcontrib>Yamashiro, Kaeli J.</creatorcontrib><creatorcontrib>Reynaga, Lizette</creatorcontrib><creatorcontrib>Hyllen, Alicia A.</creatorcontrib><creatorcontrib>de Lorimier, Arthur J.</creatorcontrib><creatorcontrib>Hassan, Maheen</creatorcontrib><creatorcontrib>Wang, Aijun</creatorcontrib><creatorcontrib>Farmer, Diana L.</creatorcontrib><creatorcontrib>Saadai, Payam</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of pediatric surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Theodorou, Christina M.</au><au>Jackson, Jordan E.</au><au>Stokes, Sarah C.</au><au>Pivetti, Christopher D.</au><au>Kumar, Priyadarsini</au><au>Paxton, Zachary J.</au><au>Matsukuma, Karen E.</au><au>Yamashiro, Kaeli J.</au><au>Reynaga, Lizette</au><au>Hyllen, Alicia A.</au><au>de Lorimier, Arthur J.</au><au>Hassan, Maheen</au><au>Wang, Aijun</au><au>Farmer, Diana L.</au><au>Saadai, Payam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair</atitle><jtitle>Journal of pediatric surgery</jtitle><addtitle>J Pediatr Surg</addtitle><date>2022-05-01</date><risdate>2022</risdate><volume>57</volume><issue>5</issue><spage>941</spage><epage>948</epage><pages>941-948</pages><issn>0022-3468</issn><eissn>1531-5037</eissn><abstract>•Myelomeningocele is associated with significant bowel and bladder dysfunction.•Fetal ovine myelomeningocele repair augmented with placental mesenchymal stem cells was associated with near-normal bowel and bladder function.
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.
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).
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.
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>35093254</pmid><doi>10.1016/j.jpedsurg.2021.12.046</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-0365-3053</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of pediatric surgery, 2022-05, Vol.57 (5), p.941-948 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Bladder function Bowel function Cellular therapy Female Fetal surgery Fetus - surgery Humans Meningomyelocele - complications Meningomyelocele - surgery Mesenchymal Stem Cells Myelomeningocele Placenta Pregnancy Sheep Sheep, Domestic Spina bifida Urinary Bladder - surgery |
| title | Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair |
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