Document Detail

A thermoreversible polymer mediates controlled release of glial cell line-derived neurotrophic factor to enhance kidney regeneration.
MedLine Citation:
PMID:  20497162     Owner:  NLM     Status:  MEDLINE    
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 degrees C but becomes a hydrogel upon heating to 37 degrees 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 degrees C and then maintained at 37 degrees C, acted as a diffuser of GDNF for more than 48 h. LacZ-transfected hMSCs and the GDNF-polymer (at 4 degrees C) were placed in the nephrogenic sites of growing rat embryos that were maintained at 37 degrees 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.
Yousof Gheisari; Takashi Yokoo; Kei Matsumoto; Akira Fukui; Naomi Sugimoto; Toya Ohashi; Tetsuya Kawamura; Tatsuo Hosoya; Eiji Kobayashi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-21
Journal Detail:
Title:  Artificial organs     Volume:  34     ISSN:  1525-1594     ISO Abbreviation:  Artif Organs     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-11     Completed Date:  2010-11-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7802778     Medline TA:  Artif Organs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  642-7     Citation Subset:  IM    
Project Laboratory for Kidney Regeneration, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.
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MeSH Terms
COS Cells
Cell Differentiation
Cercopithecus aethiops
Glial Cell Line-Derived Neurotrophic Factor / administration & dosage*
Mesenchymal Stem Cell Transplantation / methods*
Polyethylene Glycols / therapeutic use*
Polymethacrylic Acids / therapeutic use*
Rats, Sprague-Dawley
Renal Insufficiency / therapy*
Thermal Diffusion
Reg. No./Substance:
0/GDNF protein, human; 0/Glial Cell Line-Derived Neurotrophic Factor; 0/Polyethylene Glycols; 0/Polymethacrylic Acids; 111984-73-7/poly(N-isopropylacrylamide-co-butyl methacrylate)

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