Development of cell therapy strategies to overcome copper toxicity in the LEC rat model of Wilson disease.

Abstract:

AIMS:Therapeutic replacement of organs with healthy cells requires disease-specific strategies. As copper toxicosis due to ATP7B deficiency in Wilson disease produces significant liver injury, disease-specific study of transplanted cell proliferation will offer insights into cell and gene therapy mechanisms. MATERIALS & METHODS:We used Long-Evans Cinnamon (LEC) rats to demonstrate the effects of liver preconditioning with radiation and ischemia reperfusion, followed by transplantation of healthy Long-Evans Agouti rat hepatocytes and analysis of hepatic atp7b mRNA, bile copper, liver copper and liver histology. RESULTS:LEC rats without cell therapy or after transplantation of healthy cells without liver conditioning accumulated copper and showed liver disease during the study period. Liver conditioning incorporating hepatic radiation promoted transplanted cell proliferation and reversed Wilson disease parameters, although with interindividual variations and time lags for improvement, which were different from previous results of liver repopulation in healthy animals. CONCLUSION:Cell therapy will correct genetic disorders characterized by organ damage. However, suitable mechanisms for inducing transplanted cell proliferation will be critical for therapeutic success.

journal_name

Regen Med

journal_title

Regenerative medicine

authors

Malhi H,Joseph B,Schilsky ML,Gupta S

doi

10.2217/17460751.3.2.165

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

165-73

issue

2

eissn

1746-0751

issn

1746-076X

journal_volume

3

pub_type

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