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Neurologic Improvement Detected in Rats Receiving Stem Cell Transplant

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Neurologic Improvement Detected in Rats Receiving Stem Cell Transplant

In a study to be presented today at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting ™, in Dallas, Texas, researchers will report that early transplantation of human placenta-derived mesenchymal stem cells into the lateral ventricles of neonatal rats with birth-related brain damage is possible, and that the donor cells can survive and migrate in the recipient’s brain.  The study was designed to have the rat’s brain damage mimic brain injury in infants with very low birth weight.

One of the major causes of neonatal brain damage is preterm delivery.  Despite enormous efforts to prevent it, brain injury accounts for a major part of the clinical problems experienced by survivors of premature birth.  The enormity of this problem is indicated by the occurrence of: cognitive, behavioral, attention related and/or socialization deficits in twenty-five to fifty percent of cases in this group; and major motor deficits in five to ten percent of cases in this group.

The majority of neonatal encephalopathy cases are found in infants with a very low birth weight, and include both hypoxia-ischemia and inflammation, a double-hit.  Approximately 63,000 infants are born in the United States with a very low birth weight (one to five percent of all live births).  In order to understand the effect of such a double-hit insult in very premature infants, this study, Early Intracranial Mesenchymal Stem Cell Therapy After a Perinatal Rat Brain Damage, was undertaken to investigate the neuroprotective effects of mesenchymal stem cells therapy on postnatal rats, whose injury was designed to mimic brain injury in infants with a very low birth weight.

“Stem cells are a promising source for transplant after a brain injury because they have the ability to divide throughout life and grow into any one of the body’s more than 200 cell types, which can contribute to the ability to renew and repair tissues,” said Martin Müller, MD, with the University of Bern, Obstetrics and Gynecology, Bern, Switzerland, and one of the study’s authors.  “In our study, the donor cells survived, homed and migrated in the recipient brains and neurologic improvement was detected.”

Assessment of the post-experiment brain damage indicated a neuroprotective effect of mesenchymal stem cell transplantation and a combination of mesenchymal stem cell and erythropoietin (a modulator substance the subjects received on postnatal days six, seven and eight) therapy.

In addition to Müller, the study was conducted by Andreina Schoeberlein, Ursula Reinhart, Ruth Sager and Marianne Messerli, University of Bern, Obstetrics and Gynecology, Bern, Switzerland; and Daniel Surbek, University Hospital of Bern, Obstetrics and Gynecology, Bern, Switzerland.

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A copy of the abstract is available at http://www.smfmnewsroom.org/annual-meeting/2011-meeting-abstracts/.  For interviews please contact Vicki Bendure at Vicki@bendurepr.com, 540-687-3360 (office) or 202-374-9259 (cell), or Jacqueline Boggess at jacqueline@bendurepr.com, 540-687-5399 (office) or 202-738-3054 (cell).

The Society for Maternal-Fetal Medicine (est. 1977) is a non-profit membership group for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine.  The society is devoted to reducing high-risk pregnancy complications by providing continuing education to its 2,000 members on the latest pregnancy assessment and treatment methods.  It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine.  The group hosts an annual scientific meeting in which new ideas and research in the area of maternal-fetal medicine are unveiled and discussed.  For more information, visit www.smfm.org or www.facebook.com/SocietyforMaternalFetalMedicine.  

 

Abstract 54:

Early intracranial mesenchymal stem cell therapy after a perinatal rat brain damage
Martin Mueller 1, Andreina Schoeberlein 1, Ursula Reinhart 1,Ruth Sager 1, Marianne Messerli 1, Daniel Surbek 2

University of Bern, Obstetrics and Gynecology, Bern, Switzerland, University Hospital of Bern, Obstetrics and Gynecology, Bern, Switzerland

OBJECTIVE: The aim of the study was to asses therapeutic effects of an early intracranial mesenchymal stem cell transplantation after induction of perinatal brain injury in an perinatal rat model.

STUDY DESIGN: The study was conducted in a sham controlled design. Subcutaneous administration of LPS from E. coli and ligation of the left carotid artery followed by 30 minutes of hypoxia (8% O2) on postnatal d4 Wistar rats induced a perinatal brain damage. On postnatal d6 pups were anesthetized again and 250000 human placentaderived mesenchymal stem cells (MSC) were injected into the lateral ventricle using a stereotactic frame. A second therapy group additionally received erythropoietin (EPO) (1000 U/kg bw, ip) on postnatal d6,7 and d8 after the transplantation. Donor MSC were assessed by histology and immunohistochemistry using an anti-human HLAABC antibody on postnatal d16.

RESULTS: 96% of the animals survived the procedures (22/23). Donor cells were detected in the brain ventricle and periventricular white matter post transplantation. Morphologic assessment of the damage by microscopic score indicates a neuroprotective effect of MSC transplantation and combination of MSCs and EPO therapy.

CONCLUSION: Early transplantation of human placenta-derived MSC into the lateral ventricles of neonatal rats /EPO is possible. Donor cells survived, homed and migrated in the recipient brains and a neuroprotective activity seems possible. Proliferation and differentiation analysis and functional tests will assess the therapeutic effects of stem cell transplantation with a supportive erythropoietin therapy.

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