Adult stem cell derived conditioned medium and/or adult stem cells for use in the therapeutic treatment of a tumor disease

• US 9,034,335 B2
• Filed: 12/07/2010
• Issued: 05/19/2015
• Est. Priority Date: 12/09/2009
• Status: Active Grant

• Current Assignee: Fresenius Medical Care Deutschland GmbH (Fresenius SE & Co. KGaA)
• Original Assignee: Fresenius Medical Care Deutschland GmbH (Fresenius SE & Co. KGaA)
• Inventors: Tetta, Ciro, Camussi, Giovanni, Herrera Sanchez, Maria Beatriz, Fonsato, Valentina
• Primary Examiner(s): BELYAVSKYI, MICHAIL A
• Application Number:
  US13/514,719
• Publication Number:
  US 20120251489A1
• Time in Patent Office: 1,624 Days
• Field of Search: None
• US Class Current: 424/184.1
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/35 Fat tissue; Adipocytes; Stromal cells; Connective tissues adipose-derived stem cells A61K35/28; collagen A61K38/39
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 2500/84 from mammals
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2502/14 hepatocytes
• CPC Class Codes: C12N 5/0672 Stem cells; Progenitor cells; Precursor cells; Oval cells

Abstract

The invention is in the field of therapeutic treatment of tumors. It has been found that the conditioned medium resulting from culturing an adult stem cell capable of differentiating into a plurality of differentiated cell types in a liquid cell culture medium and/or the adult stem cell from which the conditioned medium is obtainable, exert a remarkable anti-tumor effect. The adult stem cell derived conditioned medium preferred in this therapeutic application is a cell free conditioned medium derived from a human liver stem cell (HLSC).

Claims

1. A method for therapeutic treatment of a tumour disease comprising the steps of:

providing a conditioned medium which includes a plurality of cell-secreted proteins and which is obtainable by culturing in a liquid cell culture medium an adult non-oval liver stem cell capable of differentiating into a plurality of differentiated cell types; and

using the conditioned medium for the therapeutic treatment of a tumour disease.

2. The method according to claim 1, which includes providing a cell fraction containing the adult stem cell from which the conditioned medium is obtained.

3. The method according to claim 1, wherein the step of providing a conditioned medium includes providing a conditioned medium that is cell free.

4. The method according to claim 3, wherein the step of providing a conditioned medium includes obtaining the conditioned medium by a method including the steps of:

(i) culturing an adult stem cell capable of differentiating into a plurality of differentiated cell types in a liquid cell culture medium for a predetermined period of time; and

(ii) removing the cell fraction from the liquid cell culture medium, thereby obtaining a cell free conditioned medium which includes a plurality of cell-secreted proteins.

5. The method according to claim 4, wherein the step of removing the cell fraction from the liquid cell culture medium is performed by centrifugation or filtration.

6. The method according to claim 5, further comprising the step of subjecting the liquid cell culture medium to ultracentrifugation at a g-force of between about 20,000 and about 300,000 g.

7. The method according to claim 4, wherein the method of obtaining the conditioned medium further comprises the step of:

(iii) removing from the cell free conditioned medium the fraction of matter having a nominal molecular weight lower than 3 kDa.

8. The method according to claim 7, wherein the step of removing includes removing the fraction of matter having a nominal molecular weight lower than 3 kDa from the cell free conditioned medium by ultrafiltration.

9. The method according to claim 7, wherein the method further comprises the step of treating the cell free conditioned medium obtained in step (ii) or in step (iii) with RNase.

10. The method according to claim 1, wherein the non-oval liver stem cell is capable of differentiating into a mature liver cell, an insulin-producing cell, an osteogenic cell and an epithelial cell.

11. The method according to claim 1, wherein the adult non-oval liver stem cell capable of differentiating into a plurality of differentiated cell types is a human cell.

12. The method according to claim 1, wherein the step of therapeutic treatment includes therapeutically treating a tumour disease selected from the group consisting of liver tumour, epithelial tumour, breast tumour, lung tumour, prostate tumour, gastric tumour, and colon tumour.

13. The method according to claim 1, wherein the step of therapeutic treatment includes therapeutically treating a tumour disease selected from the group consisting of hepatoma, Kaposi'"'"'s sarcoma and breast adenocarcinoma.

17. The method according to claim 6, wherein the liquid cell culture medium is subjected to ultracentrifugation at a g-force between about 80,000 and 200,000 g.

14. A method including the step of using a medicament, wherein the medicament is

a) a conditioned medium which includes a plurality of cell-secreted proteins and which is obtainable by culturing in a liquid cell culture medium an adult non-oval liver stem cell capable of differentiating into a plurality of differentiated cell types or

b) the adult non-oval liver stem cell,

for the therapeutic treatment of a tumour disease.

15. The method according to claim 14, wherein the medicament is used for local or systemic administration.

16. The method according to claim 15, wherein the medicament is administrated by injection.