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Jianqiang Ding, Govardhana R. Yannam, Namita Roy-Chowdhury, et al.

【News】 α1-Antitrypsin deficiency is an inherited condition that causes liver disease and emphysema. The normal function of this protein, which is synthesized by the liver, is to inhibit neutrophil elastase, a protease that degrades connective tissue of the lung. In the classical form of the disease, inefficient secretion of a mutant α1-antitrypsin protein (AAT-Z) results in its accumulation within hepatocytes and reduced protease inhibitor activity, resulting in liver injury and pulmonary emphysema. Because mutant protein accumulation increases hepatocyte cell stress, we investigated whether transplanted hepatocytes expressing wild-type AAT might have a competitive advantage relative to AAT-Z-expressing hepatocytes, using transgenic mice expressing human AAT-Z. Wild-type donor hepatocytes replaced 20%~98% of mutant host hepatocytes, and repopulation was accelerated by injection of an adenovector expressing hepatocyte growth factor. Spontaneous hepatic repopulation with engrafted hepatocytes occurred in the AAT-Z-expressing mice even in the absence of severe liver injury. Donor cells replaced both globule-containing and globule-devoid cells, indicating that both types of host hepatocytes display impaired proliferation relative to wild-type hepatocytes. These results suggest that wild-type hepatocyte transplantation may be therapeutic for AAT-Z liver disease and may provide an alternative to protein replacement for treating emphysema in AAT-ZZ individuals.
【Comments】 The current treatment of α1-Antitrypsin deficiency is the life-long injection of α1-Antitrypsin produced by means of genetic engineering. The therapy is very expensive and unable to cure liver disease. The other way is the liver-lung transplantation that is used on the severest patients. This study model is one kind of positive attempts that solves liver-lung problems via hepatocyte transplantation. But currently certain effectiveness of hepatocytic group recovery was inspected only on model mice.
【Reference】 Journal of Clinical Investigation, 2011; 121(5):1930~1934.