Bone marrow stem cell therapy partially ameliorates pathological consequences in livers of mice expressing mutant human α1-antitrypsin.

Imported: 06 Jan '17 | Published: 06 Jan '17

Prakash P Baligar, Veena V Kochat, Shailendra K SK Arindkar, Zaffar Z Equbal, Snehashish S Mukherjee, Swati S Patel, Perumal P Nagarajan, Sujata S Mohanty, Jeffrey H JH Teckman, Asok A Mukhopadhyay


Abstract: Alpha1-antitrypsin deficiency (AATD) is a genetic disease, caused by mutation of the AAT gene. Accumulation of mutated AAT protein aggregates in hepatocytes leads to endoplasmic reticulum (ER) stress resulting in impairment of liver functions and in some cases hepatocellular carcinoma, whereas decline of AAT levels in sera is responsible for pulmonary emphysema. In critical cases of liver ailments, the only option for treatment is liver transplantation, whereas AAT replacement therapy is followed in case of emphysema. As hepatocytes are the primary affected cells in AATD, we investigated whether transplantation of bone marrow-derived stem cells in transgenic mice expressing human AATZ (the Z variant of AAT) confers any competitive advantages compared to host cells for pathological improvement, if any. Mouse bone marrow (BM) progenitors and human mesenchymal stem cells (MSCs) appear to contribute in replacement of 40% and 13% host... Read More

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