Silylated biomolecule-based hydrogel for culturing cardiomyocytes and stem cells, and use of the hydrogel thereof for treating heart failure

• US 9,968,681 B2
• Filed: 06/04/2012
• Issued: 05/15/2018
• Est. Priority Date: 06/03/2011
• Status: Active Grant

• Current Assignee: Institut National De La Sante Et De La Recherche Medicale (Inserm) (Allianz Global Investors GmbH), Chu Nantes, Universite De Nantes
• Original Assignee: Institut National De La Sante Et De La Recherche Medicale (Inserm) (Allianz Global Investors GmbH), Chu Nantes, Universite De Nantes
• Inventors: Weiss, Pierre, Mathieu, Eva, Guicheux, Jrme, Lemarchand, Patricia
• Primary Examiner(s): Yamasaki, Robert J
• Application Number:
  US14/123,286
• Publication Number:
  US 20140161775A1
• Time in Patent Office: 2,171 Days
• Field of Search: None
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• 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 35/34 Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes vascular smooth muscle A61K35/44
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: C12N 2533/20 Small organic molecules
• CPC Class Codes: C12N 2533/72 Chitin, chitosan
• CPC Class Codes: C12N 2533/78 Cellulose
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0657 Cardiomyocytes; Heart cells

Abstract

The present invention relates to the use of an hydrogel comprising silylated biomolecule for the three-dimensional culture of cardiomyocytes or stem cells which are able to differentiate into cardiomyocytes, and to an aqueous composition comprising i) cardiomyocytes or stem cells which are able to differentiate into cardiomyocytes, and ii) a hydrogel comprising silylated biomolecule, for use for treating heart failure, in particular heart failure following myocardial infarction.

Claims

1. A kit for obtaining an aqueous composition that is usable in a method of treating heart failure, said kit comprising i) mesenchymal stem cells which are able to differentiate into cardiomyocytes, and ii) a hydrogel solution which comprises a silylated biomolecule capable of forming a pH dependent self-reticulating hydrogel, wherein the hydrogel solution comprises agents which induce cardiomyocyte differentiation of the mesenchymal stem cells.

2. The kit according to claim 1, further comprising instructions for the use of said kit in preparing a composition comprising:

i) the mesenchymal stem cells which are able to differentiate into cardiomyocytes; and

ii) the hydrogel solution comprising a silylated biomolecule;

said composition being suitable for injection into myocardium.

3. The kit according to claim 1, wherein the silylated biomolecule is selected from the group consisting of a silylated polysaccharide, a silylated peptide a silylated protein, and an association of two different biomolecules selected from a silylated polysaccharide, a silylated peptide, and a silylated protein.

4. The kit according to claim 3, wherein the silylated polysaccharide is selected from the group consisting of:

silylated cellulose, silylated hydroxypropylmethylcellulose (HPMC), silylated hydroxyethylcellulose (HEC), silylated carboxymethylcellulose (CMC), silylated pectin, silylated chitosan and silylated hyaluronic acid.

5. The kit according to claim 1, wherein the hydrogel solution of (ii) has undergone three weeks of reticulation and has the following rheological characteristics at a pH value of 7.4:

a compressive modulus at 5% stress from 220 to 430 Pa;

a storage modulus G′

from 235 to 450 Pa;

a loss modulus G″

from 29 to 60 Pa;

a gel point from 23.8 to 30.6 minutes.

6. A kit for the three-dimensional culture of mesenchymal stem cells which are able to differentiate into cardiomyocytes, said kit comprising i) mesenchymal stem cells which are able to differentiate into cardiomyocytes, and ii) a hydrogel solution which comprises a silylated biomolecule capable of forming a pH dependent self-reticulating hydrogel, wherein the hydrogel solution comprises agents which induce cardiomyocyte differentiation of the mesenchymal stem cells.

7. The kit according to claim 6, wherein the silylated biomolecule is selected from the group consisting of a silylated polysaccharide, a silylated peptide a silylated protein, and an association of two different biomolecules selected from a silylated polysaccharide, a silylated peptide, and a silylated protein.

8. The kit according to claim 7, wherein the silylated polysaccharide is selected from the group consisting of:

silylated cellulose, silylated hydroxypropylmethylcellulose (HPMC), silylated hydroxyethylcellulose (HEC), silylated carboxymethylcellulose (CMC), silylated pectin, silylated chitosan and silylated hyaluronic acid.

9. The kit according to claim 6, wherein the hydrogel solution (ii) has undergone three weeks of reticulation and has the following rheological characteristics at a pH value of 7.4:

a compressive modulus at 5% stress from 220 to 15 000 Pa;

a storage modulus G′

from 235 to 10 000 Pa;

a loss modulus G″

from 29 to 1000 Pa;

a gel point from 5 to 45 minutes.