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- Title
A Thermoreversible Polymer Mediates Controlled Release of Glial Cell Line-Derived Neurotrophic Factor to Enhance Kidney Regeneration.
- Authors
Gheisari, Yousof; Yokoo, Takashi; Matsumoto, Kei; Fukui, Akira; Sugimoto, Naomi; Ohashi, Toya; Kawamura, Tetsuya; Hosoya, Tatsuo; Kobayashi, Eiji
- Abstract
Previously, we reported that human mesenchymal stem cells (hMSCs) that were cultivated in growing embryos differentiated in an appropriate developmental milieu, thereby facilitating the development of a functional renal unit. However, this approach required transfection with an adenovirus that expressed glial cell line-derived neurotrophic factor (GDNF) to enhance the development of hMSC-derived renal tissue, and safety issues restrict the clinical use of such viral vectors. To circumvent this problem, we tested an artificial polymer as a means to diffuse GDNF. This GDNF-polymer, which exists in liquid form at 4°C but becomes a hydrogel upon heating to 37°C, was used as a thermoreversible switch, allowing the injection of hMSCs at low viscosity using a mouth pipette, with subsequent slow diffusion of GDNF as it solidified. The polymer, which was dissolved in a solution of GDNF at 4°C and then maintained at 37°C, acted as a diffuser of GDNF for more than 48 h. LacZ-transfected hMSCs and the GDNF-polymer (at 4°C) were placed in the nephrogenic sites of growing rat embryos that were maintained at 37°C. Forty-eight hours later, the resultant kidney anlagen were dissected out and allowed to continue developing for 6 days in vitro. Whole-organ X-Gal staining and fluorescence activated cell sorter analysis showed that the number of hMSC-derived cells was significantly increased in developed anlagen that have been generated from hMSCs plus GDNF-polymer compared with those from hMSCs plus GDNF-containing medium and was comparable to those from adenovirus-transfected hMSCs. These findings suggest that the GDNF-polymer can be used as a diffuser of GDNF for kidney organogenesis.
- Subjects
KIDNEY disease treatments; MORPHOGENESIS; ADENOVIRUSES; EMBRYOS; HYDROGELS
- Publication
Artificial Organs, 2010, Vol 34, Issue 8, p642
- ISSN
0160-564X
- Publication type
Article
- DOI
10.1111/j.1525-1594.2009.00928.x