15-07-08(4:10:51)
Authors:
Schmidt UR 1,2, Wagner DC 1,2, Förschler A 3, Kranz A 2, Kamprad M 1, Egger D 4, Emmrich F 1,2,5 and Boltze J 1,2,5
Institutions:
1 Institute for Clinical Immunology and Transfusion Medicine, Leipzig, Germany
2 Fraunhofer-Institute for Cell Therapy and Immunology, Leipzig, Germany
3 Department of Neuroradiology, Clinic of Diagnostic Radiology, Leipzig, Germany
4 VITA34 Inc., BBZ, Leipzig, Germany
5 Translational Centre for Regenerative Medicine, Leipzig, Germany
Title of abstract : Intravenous Cell Treatment of Stroke by Human Umbilical Cord Blood Cells: Investigation of the Therapeutic Time Window
Abstract text:
Background and purpose
Experimental treatment strategies using human umbilical cord blood cells (HUCBC) are expected to be promising options for alternative stroke therapies. Current studies suggest a time window of at least 48 hours; however, the extent of this window is unknown. This study aimed to determine the time window of intravenous HUCBC stroke treatment after permanent middle cerebral artery occlusion (MCAO).
Methods
Male spontaneously hypertensive rats underwent MCAO and were randomly assigned to intravenous HUCBC administration at 4h, 24h, 72h, 120h and 14d. Treatment efficacy was monitored by magnetic resonance imaging on Days 1, 8 and 29 following MCAO as well as by behavioral phenotyping. On Day 30, brains were investigated for glial scar development and homing of HUCBC.
Results
Transplantation within a 72h time window effectuated an early improvement of functional recovery as well as a reduction of brain atrophy and glial scarring. Cell transplantation 120h post MCAO provoked a delayed functional recovery without changes in the brain atrophy rate and glial reactivity, while transplantation of HUCBC after 14 days did not show any benefit. However, no evidence for intracerebrally localized HUCBC was found.
Conclusions
Our results indicate a noticeably larger time window of HUCBC-based stroke therapy as compared to conventional approaches. Data furthermore indicate that neuronal or glial differentiation and integration of administered cells is not responsible for functional improvement and lesion size reduction.
