PREPARATION OF HUMAN ALLOGENEIC LIVER-DERIVED PROGENITOR CELLS

1 . A process for the manufacture of a population of human allogeneic liver-derived progenitor cells (HALPC), comprising the steps of:

(a) providing a suspension of primary liver cells obtained from a human liver;

(b) culturing the primary liver cells comprised in said suspension under conditions that cause the emergence of a population of cells having an elongated shape and mesenchymal morphology;

(c) culturing the cell population emerged in step (b) under conditions that cause its expansion;

(d) harvesting the expanded cell population obtained in step (c); wherein said cells of the expanded cell population obtained in step (c) are human allogeneic liver-derived progenitor cells (HALPC) that express at least one mesenchymal marker selected from CD90, CD44, CD73, CD13, CD140b, CD29, vimentin and alpha-smooth muscle actin (ASMA), and optionally express at least one hepatic marker and/or exhibit a liver-specific activity;

wherein step (c) comprises the use of a bioreactor and a microcarrier.

2 . The process of claim 1 , further comprising a step of

(e) establishing that said cells of the expanded cell population obtained in step (c) are human allogeneic liver-derived progenitor cells (HALPC) that express at least one mesenchymal marker selected from CD90, CD44, CD73, CD13, CD140b, CD29, vimentin and alpha-smooth muscle actin (ASMA), and optionally express at least one hepatic marker and/or exhibit a liver-specific activity.

3 . The process of claim 1 , wherein the human allogeneic liver-derived progenitor cells obtained in step (c) or (d) express at least one mesenchymal marker selected from CD90, CD44, CD73, CD13, CD140b, CD29, vimentin and α-smooth muscle actin (ASMA); and secrete HGF.

4 . The process of claim 1 , wherein the human allogeneic liver-derived progenitor cells obtained in step (c) or (d) further secrete PGE2.

5 . The process of claim 1 , wherein the human allogeneic liver-derived progenitor cells obtained in step (c) or (d) are

(i) positive for α-smooth muscle actin (ASMA), CD140b and optionally albumin (ALB);

(ii) negative for Cytokeratin-19 (CK-19).

6 . The process of claim 1 , wherein the human allogeneic liver-derived progenitor cells obtained in step (c) or (d) are positive for CD90, CD73, vimentin and ASMA.

7 . The process of claim 1 , wherein the microcarrier is selected from a polystyrene, gelatin, cross-linked dextran, cross-linked cellulose, polyethylene with silica, polyvinyl alcohol (PVA) and a digestible microcarrier.

8 . The process according to claim 1 , wherein the microcarrier is coated with a biocompatible material that facilitates the adhesion of the cells, optionally wherein the coating is a synthetic coating, a synthetic polymer, a biopolymer, or a chemical surface modification of the microcarrier.

9 . The process according to claim 1 , wherein the microcarrier is coated with a surface treatment selected from peptide coating, such as collagen, gelatin, or fibronectin; a glass coating such as high-silica glass; and a chemical or surface-charge coating such as cationic trimethyl ammonium, or diethylaminoethyl.

10 . The process according to claim 1 , wherein the microcarrier is a bead having a volume median diameter in the range of 90 to 400 μm.

11 . The process according to claim 1 , wherein the microcarrier has an average density of between 1.02 and 1.12 g/cm 3 .

12 . The process according to claim 1 , wherein the microcarrier has a surface area of between 300 and 600 cm 2 /g.

13 . The process according to claim 1 , wherein the bioreactor is a stirred tank bioreactor, preferably a horizontal stirred tank bioreactor or a vertical stirred tank reactor.

14 . The process according to claim 1 , wherein the volume of the bioreactor is between 0.2 and 500 liters.

15 . The process according to claim 1 , wherein in step (c) the cells are seeded at a density of 1000-8000 cells/cm 2 .

16 . The process according to claim 1 , wherein step (c) comprises passaging the cell population emerged in step (b) at least twice and not more than three times.

17 . The process according to claim 1 , wherein the first passage of step (c) is performed in a small bioreactor having a capacity of 0.5 to 10 liters.

18 . The process according to claim 1 , wherein the last passage of step (c) is performed in a bioreactor having a capacity between 10 and 500 liters.

19 . An isolated population of human allogeneic liver-derived progenitor cells obtainable by the process according to claim 1 .

20 . The isolated population of human allogeneic liver-derived progenitor cells according to claim 19 for use in the treatment of a liver disease.