Z Geburtshilfe Neonatol 2011; 215 - FV12_04
DOI: 10.1055/s-0031-1293279

Placenta-derived Mesenchymal Stem Cells for the Neuroregeneration in a Rat Perinatal Brain Injury Model

M Müller 1, A Schoeberlein 1, U Reinhart 1, R Sager 1, M Messerli 1, D Surbek 1
  • 1Universitäts-Frauenklinik, Inselspital Bern und Departement Klinische Forschung, Bern, Schweiz

Aim: Perinatal brain injury in the premature infant often leads to severe longterm disability. Stem cell transplantation has been proposed as a therapy for neurodegenerative diseases.The aim of this study is to assess the therapeutic potential of stem cell transplantation in an animal model of peripartal brain damage.

Perinatal brain injury model: Perinatal brain injury was induced in newborn (postnatal days 2–7) Wistar rats by the following procedure (Fig. 1).

Stem cell transplantation: Injured and sham-treated animals were transplanted 24h, 1 week or 4 week post injury using a stereotaxic frame. Mesenchymal stem cells (250’000 cells) were injected into the left lateral ventricle (Fig. 2). The animals were sacrificed 3–4h, 1, 2 and 4 weeks after transplantation.

Detection of donor cells: Donor human MSC are detected by immunohistochemistry using a mouse anti-human HLA Class 1 ABC antibody.

Homing: Cells distributed over the ventricularsystem within 4h (Fig. 3 A-B). One, 2 and 4 weeks after Tx, human cells had emigrated from the ventricles and integrated into the surrounding tissue (Fig. 3 C-H). Cells were mainly found in paraventricular areas of VL of the ipsilateral hemisphere (2/3 ofanimals) and the 3rd and 4th ventricle (1/3 of animals).

Survival: The overall survival of injured animals was 52%. Some animals died within the critical time frame of 24h post injury (24h survival: 74%). While most of the untreatedanimals with brain injury survived (88.9%), 64.3% of transplanted animals survived untilsacrifice. All animals with sham injury (PBS injection, anesthesia, no treatment) survived the procedure.

Conclusion: Human stem cells were successfully transplanted into the VL and into the paraventricular zone of neonatal rats’ brains. They survive, home and migrate in the recipients brain, and lead to a cellular mobilization in the recipient. Functional tests will assess therapeutic effects of stem cell transplantation.

Hypoxia-Ischemia - Mesenchymal Stem Cells - Neuroregeneration