Neural stem cell treatment for perinatal brain injury: A systematic review and meta‐analysis of preclinical studies

Abstract Perinatal brain injury can lead to significant neurological and cognitive deficits and currently no therapies can regenerate the damaged brain. Neural stem cells (NSCs) have the potential to engraft and regenerate damaged brain tissue. The aim of this systematic review was to evaluate the p...

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Autores principales:	Madeleine J. Smith, Madison Claire Badawy Paton, Michael C. Fahey, Graham Jenkin, Suzanne L. Miller, Megan Finch‐Edmondson, Courtney A. McDonald
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	animal models cell transplantation immunosuppression neural differentiation stem cells tissue‐specific stem cells Medicine (General) R5-920 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/0061f57653f24b59ac6f72966506fbc0
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spelling	oai:doaj.org-article:0061f57653f24b59ac6f72966506fbc02021-12-03T12:11:46ZNeural stem cell treatment for perinatal brain injury: A systematic review and meta‐analysis of preclinical studies2157-65802157-656410.1002/sctm.21-0243https://doaj.org/article/0061f57653f24b59ac6f72966506fbc02021-12-01T00:00:00Zhttps://doi.org/10.1002/sctm.21-0243https://doaj.org/toc/2157-6564https://doaj.org/toc/2157-6580Abstract Perinatal brain injury can lead to significant neurological and cognitive deficits and currently no therapies can regenerate the damaged brain. Neural stem cells (NSCs) have the potential to engraft and regenerate damaged brain tissue. The aim of this systematic review was to evaluate the preclinical literature to determine whether NSC administration is more effective than controls in decreasing perinatal brain injury. Controlled interventional studies of NSC therapy using animal models of perinatal brain injury were identified using MEDLINE and Embase. Primary outcomes were brain infarct size, motor, and cognitive function. Data for meta‐analysis were synthesized and expressed as standardized mean difference (SMD) with 95% confidence intervals (CI), using a random effects model. We also reported secondary outcomes including NSC survival, migration, differentiation, and effect on neuroinflammation. Eighteen studies met inclusion criteria. NSC administration decreased infarct size (SMD 1.09; CI: 0.44, 1.74, P = .001; I2 = 74%) improved motor function measured via the impaired forelimb preference test (SMD 2.27; CI: 0.85, 3.69, P = .002; I2 = 86%) and the rotarod test (SMD 1.88; CI: 0.09, 3.67, P = .04; I2 = 95%). Additionally, NSCs improved cognitive function measured via the Morris water maze test (SMD of 2.41; CI: 1.16, 3.66, P = .0002; I2 = 81%). Preclinical evidence suggests that NSC therapy is promising for the treatment of perinatal brain injury. We have identified key knowledge gaps, including the lack of large animal studies and uncertainty regarding the necessity of immunosuppression for NSC transplantation in neonates. These knowledge gaps should be addressed before NSC treatment can effectively progress to clinical trial.Madeleine J. SmithMadison Claire Badawy PatonMichael C. FaheyGraham JenkinSuzanne L. MillerMegan Finch‐EdmondsonCourtney A. McDonaldWileyarticleanimal modelscell transplantationimmunosuppressionneural differentiationstem cellstissue‐specific stem cellsMedicine (General)R5-920CytologyQH573-671ENStem Cells Translational Medicine, Vol 10, Iss 12, Pp 1621-1636 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	animal models cell transplantation immunosuppression neural differentiation stem cells tissue‐specific stem cells Medicine (General) R5-920 Cytology QH573-671
spellingShingle	animal models cell transplantation immunosuppression neural differentiation stem cells tissue‐specific stem cells Medicine (General) R5-920 Cytology QH573-671 Madeleine J. Smith Madison Claire Badawy Paton Michael C. Fahey Graham Jenkin Suzanne L. Miller Megan Finch‐Edmondson Courtney A. McDonald Neural stem cell treatment for perinatal brain injury: A systematic review and meta‐analysis of preclinical studies
description	Abstract Perinatal brain injury can lead to significant neurological and cognitive deficits and currently no therapies can regenerate the damaged brain. Neural stem cells (NSCs) have the potential to engraft and regenerate damaged brain tissue. The aim of this systematic review was to evaluate the preclinical literature to determine whether NSC administration is more effective than controls in decreasing perinatal brain injury. Controlled interventional studies of NSC therapy using animal models of perinatal brain injury were identified using MEDLINE and Embase. Primary outcomes were brain infarct size, motor, and cognitive function. Data for meta‐analysis were synthesized and expressed as standardized mean difference (SMD) with 95% confidence intervals (CI), using a random effects model. We also reported secondary outcomes including NSC survival, migration, differentiation, and effect on neuroinflammation. Eighteen studies met inclusion criteria. NSC administration decreased infarct size (SMD 1.09; CI: 0.44, 1.74, P = .001; I2 = 74%) improved motor function measured via the impaired forelimb preference test (SMD 2.27; CI: 0.85, 3.69, P = .002; I2 = 86%) and the rotarod test (SMD 1.88; CI: 0.09, 3.67, P = .04; I2 = 95%). Additionally, NSCs improved cognitive function measured via the Morris water maze test (SMD of 2.41; CI: 1.16, 3.66, P = .0002; I2 = 81%). Preclinical evidence suggests that NSC therapy is promising for the treatment of perinatal brain injury. We have identified key knowledge gaps, including the lack of large animal studies and uncertainty regarding the necessity of immunosuppression for NSC transplantation in neonates. These knowledge gaps should be addressed before NSC treatment can effectively progress to clinical trial.
format	article
author	Madeleine J. Smith Madison Claire Badawy Paton Michael C. Fahey Graham Jenkin Suzanne L. Miller Megan Finch‐Edmondson Courtney A. McDonald
author_facet	Madeleine J. Smith Madison Claire Badawy Paton Michael C. Fahey Graham Jenkin Suzanne L. Miller Megan Finch‐Edmondson Courtney A. McDonald
author_sort	Madeleine J. Smith
title	Neural stem cell treatment for perinatal brain injury: A systematic review and meta‐analysis of preclinical studies
title_short	Neural stem cell treatment for perinatal brain injury: A systematic review and meta‐analysis of preclinical studies
title_full	Neural stem cell treatment for perinatal brain injury: A systematic review and meta‐analysis of preclinical studies
title_fullStr	Neural stem cell treatment for perinatal brain injury: A systematic review and meta‐analysis of preclinical studies
title_full_unstemmed	Neural stem cell treatment for perinatal brain injury: A systematic review and meta‐analysis of preclinical studies
title_sort	neural stem cell treatment for perinatal brain injury: a systematic review and meta‐analysis of preclinical studies
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/0061f57653f24b59ac6f72966506fbc0
work_keys_str_mv	AT madeleinejsmith neuralstemcelltreatmentforperinatalbraininjuryasystematicreviewandmetaanalysisofpreclinicalstudies AT madisonclairebadawypaton neuralstemcelltreatmentforperinatalbraininjuryasystematicreviewandmetaanalysisofpreclinicalstudies AT michaelcfahey neuralstemcelltreatmentforperinatalbraininjuryasystematicreviewandmetaanalysisofpreclinicalstudies AT grahamjenkin neuralstemcelltreatmentforperinatalbraininjuryasystematicreviewandmetaanalysisofpreclinicalstudies AT suzannelmiller neuralstemcelltreatmentforperinatalbraininjuryasystematicreviewandmetaanalysisofpreclinicalstudies AT meganfinchedmondson neuralstemcelltreatmentforperinatalbraininjuryasystematicreviewandmetaanalysisofpreclinicalstudies AT courtneyamcdonald neuralstemcelltreatmentforperinatalbraininjuryasystematicreviewandmetaanalysisofpreclinicalstudies
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Neural stem cell treatment for perinatal brain injury: A systematic review and meta‐analysis of preclinical studies

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