gms | German Medical Science

Objective: Clinical trials of fetal striatal grafts in HD patients have so far shown a range of outcomes from no effect to disease modifying capability. Amongst the many variables involved is the age of the donor embryo at the time of grafting. In this study we aim to shed more light on how embryonic striatal cells from different aged donors develop in vivo, what kind of cell populations they contain, how and for how long grafted cells proliferate, how they reconnect with the host, and how they influence behavioural recovery.

Methods: 50 rats were used for the study of which 40 were lesioned unilaterally with QA (0.12M). 14 days later, animals received single cell suspension grafts equivalent of one whole ganglionic eminence (WGE) from E13 (n=10), E14 (n=10), E15 (n=10) donors, or remained lesioned only. Half of the animals in each grafted group were injected 3 times with BrdU (50 mg/kg) following the next 48 hours to visualize cellular proliferation, and the other half received BrdU injections according to the same schedule 21 days post-grafting. All animals were tested on the Cylinder test, the Corridor test, and on drug-induced rotation at baseline, post-lesion/ pre-grafting, and at 6 and 10 weeks post-grafting. A week prior to perfusion, a sub-group in each grafted group received fluorogold injections into the ipsilateral globus pallidus to study graft re-innervation. Animals were perfused 10 weeks post-grafting and submitted to staining and image analysis.

Results: The extent of functional recovery was shown to be dependent on i.) age of the embryonic donor tissue; ii.) context of the behavioural test; and iii.) delay between the grafting and the testing. E13 tissue grafts gave the best overall outcome.

Conclusions: The behavioural and histological data suggests that tissue from different donor age have different potential to promote functional recovery.