Buechele, Fabian and Doebroessy, Mate and Hackl, Christina and Jiang, Wei and Papazoglou, Anna and Nikkhah, Guido (2014) Two-step grafting significantly enhances the survival of foetal dopaminergic transplants and induces graft-derived vascularisation in a 6-OHDA model of Parkinson's disease. NEUROBIOLOGY OF DISEASE, 68. pp. 112-125. ISSN 0969-9961, 1095-953X
Full text not available from this repository. (Request a copy)Abstract
Following transplantation of foetal primary dopamine (DA)-rich tissue for neurorestaurative treatment of Parkinson's disease (PD), only 5-10% of the functionally relevant DAergic cells survive both in experimental models and in clinical studies. The current work tested how a two-step grafting protocol could have a positive impact on graft survival. DAergic tissue is divided in two portions and grafted in two separate sessions into the same target area within a defined time interval. We hypothesized that the first graft creates a "DAergic" microenvironment or "nest" similar to the perinatal substantia nigra that stimulates and protects the second graft. 6-OHDA-lesioned rats were sequentially transplanted with wild-type (GFP-, first graft) and transgenic (GFP +, second graft) DAergic cells in time interims of 2, 5 or 9 days. Each group was further divided into two sub-groups receiving either 200 k (low cell number groups: 2dL, 5dL, 9dL) or 400 k cells (high cell number groups: 2dH, 5dH, 9dH) as first graft. During the second transplantation, all groups received the same amount of 200 k GFP + cells. Controls received either low or high cell numbers in one single session (standard protocol). Drug-induced rotations, at 2 and 6 weeks after grafting, showed significant improvement compared to the baseline lesion levels without significant differences between the groups. Rats were sacrificed 8 weeks after transplantation for post-mortem histological assessment. Both two-step groups with the time interval of 2 days (2dL and 2dH) showed a significantly higher survival of DAergic cells compared to their respective standard control group (2dL, + 137%; 2dH, + 47%). Interposing longer intervals of 5 or 9 days resulted in the loss of statistical significance, neutralising the beneficial two-step grafting effect. Furthermore, the transplants in the 2dL and 2dH groups had higher graft volume and DA-fibre-density values compared to all other two-step groups. They also showed intense growth of GFP+ vessels - completely absent in control grafts - in regions where the two grafts overlap, indicating second-graft derived angiogenesis. In summary, the study shows that two-step grafting with a 2 days time interval significantly increases DAergic cell survival compared to the standard protocol. Furthermore, our results demonstrate, for the first time, a donor-derived neoangiogenesis, leading to a new understanding of graft survival and development in the field of cell-replacement therapies for neurodegenerative diseases. (C) 2014 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOTHELIAL GROWTH-FACTOR; CELL-SUSPENSION GRAFTS; BLOOD-BRAIN-BARRIER; NEURONS IN-VITRO; FUNCTIONAL RECOVERY; NEUROTROPHIC FACTOR; STRIATAL REINNERVATION; HEMIPARKINSONIAN RATS; VENTRAL-MESENCEPHALON; BEHAVIORAL RECOVERY; Cell transplantation; Parkinson's disease; Two-step grafting; Cell survival; Graft-derived angiogenesis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Sep 2019 07:52 |
| Last Modified: | 12 Sep 2019 07:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9856 |
Actions (login required)
 |
View Item |
