Extensive restoration of groß motor function by transplantation of human umbilical cord blood (HUCB) mononuclear cells after cerebral hypoxia-ischemia in neonatal rats

Background: We previously reported that intraperitoneal transplantation of hucb cells after cerebral ischemia in neonatal rats significantly reduced spastic paresis of the contralateral hind limb (Meier et al., Pediatr Res 2006 59: 244–249). Objectives: In this study, hucb cells were investigated for their potential to migrate specifically to a lesion site and restore impaired gros motor function in a rodent model of perinatal brain damage. Methods: 7 days old Wistar rats (P7, n=10 each group) underwent a ligation of the left common carotid artery followed by 80 mins of hypoxia; sham-operated animals served as controls. 24 hours after the insult, animals received either a sham injection of saline, intraperitoneal or intrathecal transplantation of 1×107 hucb cells. Two and 5 weeks after transplantation all animals were tested for muscle strength (rope test), forelimb use bias (cylinder test), and fine motor skills (footprints). Localization and potential differentiation of transplanted cells were visualized immunohistochemically. Western Blot analysis was performed to investigate possible molecular changes. Results: All tests showed significant differences between the control group and lesioned animals (P<0,05). However, treatment with hucb cells led to improved performance in all tested parameters. After intraperitoneal or intrathecal transplantation none of the tests revealed differences in the functional outcome. Independent of the transplantation site we observed transplanted cells exclusively in the lesioned brain area with a predominant localization in zones of abundant GFAP expression. No co-localization with neural marker proteins was found. However, analysis on the molecular level suggested effects on glial scar formation. Conclusions: Transplantation of hucb cells resulted in an extensive functional improvement of motor abilities, as determined up to six weeks after lesion. Furthermore, cells were shown to selectively migrate to the hypoxic-ischemic brain lesion irrespective of the transplantation site. However, neuronal or glial differentiation as the underlying mechanism of functional improvement seems unlikely. Putative permissive effects are currently under investigation.