Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy

Melinda Barkhuizen; Ralph van Mechelen; Marijne Vermeer; Peter Chedraui; Dean Paes; Daniel L. A. van den Hove; Bart Vaes; Robert W. Mays; Harry W. M. Steinbusch; Nicola J. Robertson; Boris W. Kramer; Antonio W. D. Gavilanes

doi:10.1016/j.bbr.2019.01.016

Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy

Melinda Barkhuizen, Ralph van Mechelen, Marijne Vermeer, Peter Chedraui, Dean Paes, Daniel L. A. van den Hove, Bart Vaes, Robert W. Mays, Harry W. M. Steinbusch, Nicola J. Robertson, Boris W. Kramer, Antonio W. D. Gavilanes^*

^*Corresponding author for this work

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

Abstract

There is an urgent need for therapies that could reduce the disease burden of preterm hypoxic-ischemic encephalopathy. Here, we evaluate the long-term effects of multipotent adult progenitor cells (MAPC) on long-term behavioral outcomes in a preterm rat model of perinatal asphyxia. Rats of both sexes were treated with two doses of MAPCs within 24 h after the insult. Locomotor, cognitive and psychiatric impairments were evaluated starting at 1.5 (juvenile) and 6 months (adult). Hypoxia-ischemia affected locomotion, cognition, and anxiety in a sex-dependent manner, with higher vulnerability observed in males. The MAPC therapy partially attenuated deficits in object recognition memory in females of all tested ages, and in the adult males. The hypoxic insult caused delayed hyperactivity in adult males, which was corrected by MAPC therapy. These results suggest that MAPCs may have long-term benefits for neurodevelopmental outcome after preterm birth and global hypoxia-ischemia, which warrants further preclinical exploration.

Original language	English
Pages (from-to)	77-81
Number of pages	5
Journal	Behavioural Brain Research
Volume	362
DOIs	https://doi.org/10.1016/j.bbr.2019.01.016
Publication status	Published - 19 Apr 2019

Keywords

Hypoxic-ischemic encephalopathy
Preterm brain
Stem cell therapy
Neurodevelopment
MESENCHYMAL STEM-CELLS
BRAIN-INJURY
PERINATAL ASPHYXIA
DOUBLE-BLIND
MATURATION
EFFICACY
INFANTS
NEURONS
SAFETY
BORN

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Barkhuizen, M., van Mechelen, R., Vermeer, M., Chedraui, P., Paes, D., van den Hove, D. L. A., Vaes, B., Mays, R. W., Steinbusch, H. W. M., Robertson, N. J., Kramer, B. W., & Gavilanes, A. W. D. (2019). Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy. Behavioural Brain Research, 362, 77-81. https://doi.org/10.1016/j.bbr.2019.01.016

@article{a76629ea1ef14477ba3c058f502c1a7e,

title = "Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy",

abstract = "There is an urgent need for therapies that could reduce the disease burden of preterm hypoxic-ischemic encephalopathy. Here, we evaluate the long-term effects of multipotent adult progenitor cells (MAPC) on long-term behavioral outcomes in a preterm rat model of perinatal asphyxia. Rats of both sexes were treated with two doses of MAPCs within 24 h after the insult. Locomotor, cognitive and psychiatric impairments were evaluated starting at 1.5 (juvenile) and 6 months (adult). Hypoxia-ischemia affected locomotion, cognition, and anxiety in a sex-dependent manner, with higher vulnerability observed in males. The MAPC therapy partially attenuated deficits in object recognition memory in females of all tested ages, and in the adult males. The hypoxic insult caused delayed hyperactivity in adult males, which was corrected by MAPC therapy. These results suggest that MAPCs may have long-term benefits for neurodevelopmental outcome after preterm birth and global hypoxia-ischemia, which warrants further preclinical exploration.",

keywords = "Hypoxic-ischemic encephalopathy, Preterm brain, Stem cell therapy, Neurodevelopment, MESENCHYMAL STEM-CELLS, BRAIN-INJURY, PERINATAL ASPHYXIA, DOUBLE-BLIND, MATURATION, EFFICACY, INFANTS, NEURONS, SAFETY, BORN",

author = "Melinda Barkhuizen and {van Mechelen}, Ralph and Marijne Vermeer and Peter Chedraui and Dean Paes and {van den Hove}, {Daniel L. A.} and Bart Vaes and Mays, {Robert W.} and Steinbusch, {Harry W. M.} and Robertson, {Nicola J.} and Kramer, {Boris W.} and Gavilanes, {Antonio W. D.}",

note = "Funding Information: We would like to thank Reint Jellema for critical reading of the manuscript. This research was partially supported by the Sistema de Investigaci{\'o}n y Desarrollo (SINDE) of the Universidad Cat{\'o}lica de Santiago de Guayaquil, Guayaquil, Ecuador , through the grant No SIU-319 : Perinatal asphyxia and stem cell treatment. M. Barkhuizen is funded by the National Research Foundation of South Africa (Grant specific reference number 98217 ) and the Foundation of Pediatrics, Maastricht University Medical Center + . The MAPC cells were donated by Athersys (R. Mays and B. Vaes). Athersys had no influence on the study design or decision to publish. Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = apr,

day = "19",

doi = "10.1016/j.bbr.2019.01.016",

language = "English",

volume = "362",

pages = "77--81",

journal = "Behavioural Brain Research",

issn = "0166-4328",

publisher = "Elsevier Science",

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Barkhuizen, M, van Mechelen, R, Vermeer, M, Chedraui, P, Paes, D , van den Hove, DLA, Vaes, B, Mays, RW, Steinbusch, HWM, Robertson, NJ, Kramer, BW & Gavilanes, AWD 2019, 'Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy', Behavioural Brain Research, vol. 362, pp. 77-81. https://doi.org/10.1016/j.bbr.2019.01.016

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T1 - Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy

AU - Barkhuizen, Melinda

AU - van Mechelen, Ralph

AU - Vermeer, Marijne

AU - Chedraui, Peter

AU - Paes, Dean

AU - van den Hove, Daniel L. A.

AU - Vaes, Bart

AU - Mays, Robert W.

AU - Steinbusch, Harry W. M.

AU - Robertson, Nicola J.

AU - Kramer, Boris W.

AU - Gavilanes, Antonio W. D.

N1 - Funding Information: We would like to thank Reint Jellema for critical reading of the manuscript. This research was partially supported by the Sistema de Investigación y Desarrollo (SINDE) of the Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador , through the grant No SIU-319 : Perinatal asphyxia and stem cell treatment. M. Barkhuizen is funded by the National Research Foundation of South Africa (Grant specific reference number 98217 ) and the Foundation of Pediatrics, Maastricht University Medical Center + . The MAPC cells were donated by Athersys (R. Mays and B. Vaes). Athersys had no influence on the study design or decision to publish. Publisher Copyright: © 2019

PY - 2019/4/19

Y1 - 2019/4/19

N2 - There is an urgent need for therapies that could reduce the disease burden of preterm hypoxic-ischemic encephalopathy. Here, we evaluate the long-term effects of multipotent adult progenitor cells (MAPC) on long-term behavioral outcomes in a preterm rat model of perinatal asphyxia. Rats of both sexes were treated with two doses of MAPCs within 24 h after the insult. Locomotor, cognitive and psychiatric impairments were evaluated starting at 1.5 (juvenile) and 6 months (adult). Hypoxia-ischemia affected locomotion, cognition, and anxiety in a sex-dependent manner, with higher vulnerability observed in males. The MAPC therapy partially attenuated deficits in object recognition memory in females of all tested ages, and in the adult males. The hypoxic insult caused delayed hyperactivity in adult males, which was corrected by MAPC therapy. These results suggest that MAPCs may have long-term benefits for neurodevelopmental outcome after preterm birth and global hypoxia-ischemia, which warrants further preclinical exploration.

AB - There is an urgent need for therapies that could reduce the disease burden of preterm hypoxic-ischemic encephalopathy. Here, we evaluate the long-term effects of multipotent adult progenitor cells (MAPC) on long-term behavioral outcomes in a preterm rat model of perinatal asphyxia. Rats of both sexes were treated with two doses of MAPCs within 24 h after the insult. Locomotor, cognitive and psychiatric impairments were evaluated starting at 1.5 (juvenile) and 6 months (adult). Hypoxia-ischemia affected locomotion, cognition, and anxiety in a sex-dependent manner, with higher vulnerability observed in males. The MAPC therapy partially attenuated deficits in object recognition memory in females of all tested ages, and in the adult males. The hypoxic insult caused delayed hyperactivity in adult males, which was corrected by MAPC therapy. These results suggest that MAPCs may have long-term benefits for neurodevelopmental outcome after preterm birth and global hypoxia-ischemia, which warrants further preclinical exploration.

KW - Hypoxic-ischemic encephalopathy

KW - Preterm brain

KW - Stem cell therapy

KW - Neurodevelopment

KW - MESENCHYMAL STEM-CELLS

KW - BRAIN-INJURY

KW - PERINATAL ASPHYXIA

KW - DOUBLE-BLIND

KW - MATURATION

KW - EFFICACY

KW - INFANTS

KW - NEURONS

KW - SAFETY

KW - BORN

U2 - 10.1016/j.bbr.2019.01.016

DO - 10.1016/j.bbr.2019.01.016

M3 - Article

C2 - 30639607

SN - 0166-4328

VL - 362

SP - 77

EP - 81

JO - Behavioural Brain Research

JF - Behavioural Brain Research

ER -