This invention relates to the efficient generation of cholangiocyte progenitor (CP) cells. Foregut stem cells (FSCs) are cultured in a hepatic induction medium comprising bone morphogenetic protein (BMP) and a TGFβ signalling inhibitor to produce a population of hepatoblasts. The hepatoblasts are then cultured in a biliary induction medium comprising fibroblast growth factor (FGF), retinoic acid and a TGFβ ligand to produce a population of cholangiocyte progenitors (CPs). The cholangiocyte progenitors (CPs) may be matured into cholangiocyte-like cells (CLCs) that display functional properties of Common Bile Duct (CBD) cholangiocytes. Methods, kits, cell populations and uses of these cell populations are provided.

This invention relates to the efficient generation of cholangiocyte progenitor (CP) cells. Foregut stem cells (FSCs) are cultured in a hepatic induction medium comprising bone morphogenetic protein (BMP) and a TGFβ signalling inhibitor to produce a population of hepatoblasts. The hepatoblasts are then cultured in a biliary induction medium comprising fibroblast growth factor (FGF), retinoic acid and a TGFβ ligand to produce a population of cholangiocyte progenitors (CPs). The cholangiocyte progenitors (CPs) may be matured into cholangiocyte-like cells (CLCs) that display functional properties of Common Bile Duct (CBD) cholangiocytes. Methods, kits, cell populations and uses of these cell populations are provided.

The present invention provides methods for reducing or eliminating a patient's need for lipoprotein apheresis therapy. The methods of the present invention comprise administering to a patient a pharmaceutical composition comprising a PCSK9 inhibitor. In certain embodiments, the PCSK9 inhibitor is an anti-PCSK9 antibody. The methods of the present invention are useful for treating patients with hyperlipidemia and related conditions who are currently being treated with a therapeutic regimen comprising lipoprotein apheresis (e.g., LDL apheresis or Lp(a) apheresis).

The present invention provides methods for reducing or eliminating a patient's need for lipoprotein apheresis therapy. The methods of the present invention comprise administering to a patient a pharmaceutical composition comprising a PCSK9 inhibitor. In certain embodiments, the PCSK9 inhibitor is an anti-PCSK9 antibody. The methods of the present invention are useful for treating patients with hyperlipidemia and related conditions who are currently being treated with a therapeutic regimen comprising lipoprotein apheresis (e.g., LDL apheresis or Lp(a) apheresis).

This invention relates to the expansion of primary cholangiocytes in the form of cholangiocyte organoids (COs) using culture conditions in which canonical Wnt signalling is inhibited and non-canonical Wnt/PCP signalling is potentiated. Methods of expanding primary cholangiocytes, expanded populations of cholangiocytes and medical applications of expanded cholangiocytes are provided.

This invention relates to the expansion of primary cholangiocytes in the form of cholangiocyte organoids (COs) using culture conditions in which canonical Wnt signalling is inhibited and non-canonical Wnt/PCP signalling is potentiated. Methods of expanding primary cholangiocytes, expanded populations of cholangiocytes and medical applications of expanded cholangiocytes are provided.

A use of bio-transformed bear bile powder in preparation of anti-inflammatory drugs is disclosed. The present invention carries out a comparative research on the anti-inflammatory drug activity of bio-transformed bear bile powder and natural bear bile powder. A research is made on the effect of the bio-transformed bear bile powder and natural bear bile powder on carrageenan-induced rat inflammation models, and a research is made on the effect of the bio-transformed bear bile powder on LPS-induced lung inflammation in mice. Experimental results show that the bio-transformed bear bile powder administration group obviously reduces plantar swelling of carrageenan-induced inflammation model in rats, and the effect thereof is not lower than that of the natural bear bile powder. Both the bio-transformed bear bile powder and the natural bear bile powder can significantly reduce levels of the inflammatory factors IL-6 and TNF- in the lung and the serum.

A use of bio-transformed bear bile powder in preparation of anti-inflammatory drugs is disclosed. The present invention carries out a comparative research on the anti-inflammatory drug activity of bio-transformed bear bile powder and natural bear bile powder. A research is made on the effect of the bio-transformed bear bile powder and natural bear bile powder on carrageenan-induced rat inflammation models, and a research is made on the effect of the bio-transformed bear bile powder on LPS-induced lung inflammation in mice. Experimental results show that the bio-transformed bear bile powder administration group obviously reduces plantar swelling of carrageenan-induced inflammation model in rats, and the effect thereof is not lower than that of the natural bear bile powder. Both the bio-transformed bear bile powder and the natural bear bile powder can significantly reduce levels of the inflammatory factors IL-6 and TNF- in the lung and the serum.

Polymeric poly(bile acid) (pBA) nanoparticles have enhanced avidity and affinity to bile acid receptors and are effective anti-inflammatory agents. Oral delivery results in local accumulation and retention in the pancreas, liver, and colon as well as in systemic delivery of the nanoparticles. The nanoparticles are effective in alleviating inflammation and are useful as anti-inflammatory agents to treat inflammatory diseases of the organs. The nanoparticles provide a therapeutic and prophylactic benefit via the TGR5 pathway when used alone, or a more than additive benefit when used in combination with immunosuppressant(s). The nanoparticles induce immune tolerance in autoimmune diseases and are useful therapeutics for treating inflammatory and autoimmune diseases.

Polymeric poly(bile acid) (pBA) nanoparticles have enhanced avidity and affinity to bile acid receptors and are effective anti-inflammatory agents. Oral delivery results in local accumulation and retention in the pancreas, liver, and colon as well as in systemic delivery of the nanoparticles. The nanoparticles are effective in alleviating inflammation and are useful as anti-inflammatory agents to treat inflammatory diseases of the organs. The nanoparticles provide a therapeutic and prophylactic benefit via the TGR5 pathway when used alone, or a more than additive benefit when used in combination with immunosuppressant(s). The nanoparticles induce immune tolerance in autoimmune diseases and are useful therapeutics for treating inflammatory and autoimmune diseases.