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

• US 10,632,203 B2
• Filed: 04/10/2018
• Issued: 04/28/2020
• 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: Inserm (institut national de la sant et de la recherche mdicale
• Inventors: Weiss, Pierre, Mathieu, Eva, Guicheux, Jerome, Lemarchand, Patricia
• Primary Examiner(s): Yamasaki, Robert J
• Application Number:
  US15/949,509
• Publication Number:
  US 20180221493A1
• Time in Patent Office: 749 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 method of treating heart failure including administration by injection into myocardium of an aqueous composition which has a physiological pH, said composition comprising:

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

ii) a hydrogel solution comprising from 0.8 to 1.5% w/v of silylated-hydroxypropylmethylcellulose (Si-HPMC) capable of forming a pH dependent self-reticulating hydrogel.

2. The method according to claim 1, wherein the stem cells are mesenchymal stem cells.

3. The method according to claim 1, wherein the hydrogel solution (ii) has the following rheological characteristics at a pH value of 7.4 after 3 weeks of reticulation:

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.

4. A method of treating heart failure including administration by injection into myocardium of an aqueous composition which has a physiological pH, said composition comprising:

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

ii) a hydrogel solution comprising silylated-hydroxypropylmethylcellulose (Si-HPMC), said Si-HPMC being capable of forming a pH dependent self-reticulating hydrogel,

wherein the hydrogel solution has the following rheological characteristics at a pH value of 7.4 after 3 weeks of reticulation;

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.