Cell construct comprising polymer blocks having biocompatibility and cells

• US 9,597,432 B2
• Filed: 03/01/2011
• Issued: 03/21/2017
• Est. Priority Date: 03/01/2010
• Status: Active Grant

• Current Assignee: Fujifilm Corporation (Fujifilm Holdings Corporation)
• Original Assignee: Fujifilm Corporation (Fujifilm Holdings Corporation)
• Inventors: Nakamura, Kentaro
• Primary Examiner(s): Visone, Thomas J
• Application Number:
  US13/582,362
• Publication Number:
  US 20120329157A1
• Time in Patent Office: 2,212 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61L 27/222 Gelatin
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 2533/76 Agarose, agar-agar
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

It is an object of the present invention to provide a cell three-dimensional construct that has a thickness sufficient for tissue regeneration and comprises cells uniformly distributed therein. The present invention provides a cell construct comprising polymer blocks having biocompatibility and cells, wherein the plural polymer blocks are arranged in spaces between the plural cells.

Claims

1. A cell construct comprising polymer blocks having biocompatibility and cells, wherein the polymer blocks are arranged in spaces between the cells, wherein

(i) the polymer blocks have surface irregularities and a non-uniform surface shape, and the polymer blocks are obtained by pulverizing freeze-dried product which comprises the polymer,

(ii) the polymer blocks have a size as defined by a sieve of from 20 μ

m to 150 μ

m,

(iii) the ratio between the polymer blocks and the cells is 0.00001 to 0.006 μ

g of the polymer blocks per cell; and

(iv) the thickness or diameter of the cell construct is from 400 μ

m to 3 cm.

2. The cell construct according to claim 1, wherein the polymer having biocompatibility is polypeptide, polylactic acid, polyglycolic acid, PLGA, hyaluronic acid, glycosaminoglycan, proteoglycan, chondroitin, cellulose, agarose, carboxymethylcellulose, chitin, or chitosan.

3. The cell construct according to claim 1, wherein the polymer having biocompatibility is a recombinant gelatin.

4. The cell construct according to claim 3, wherein the polymer having biocompatibility has two or more cell adhesion signals in one molecule of the polymer.

5. The cell construct according to claim 3, wherein the recombinant gelatin is represented by the formula:

A-[(Gly-X-Y)_n]_m-B

wherein A represents any amino acid or amino acid sequence;

B represents any amino acid or amino acid sequence;

each X of total n independently represents any amino acid;

each Y of total n independently represents any amino acid;

n represents an integer of 3 to 100;

m represents an integer of 2 to 10; and

each Gly-X—

Y of total n may be the same as or different from each other.

6. The cell construct according to claim 3, wherein the recombinant gelatin has the amino acid sequence represented by SEQ ID NO:

1.

7. A method for producing a cell construct according to claim 1, which comprises a step of incubating a mixture of polymer blocks having biocompatibility and a cell-containing culture solution.

8. The method according to claim 7, wherein the step of incubating a mixture of polymer blocks having biocompatibility and a cell-containing culture solution comprises exchanging a medium with a differentiation or growth medium.

9. The method according to claim 7, wherein the step of incubating a mixture of polymer blocks having biocompatibility and a cell-containing culture solution further comprises further adding polymer blocks having biocompatibility.

10. A cell construct which is obtained by fusion of a plurality of the cell constructs according to claim 1.

11. A method for producing a cell construct which is obtained by fusion of a plurality of the cell constructs according to claim 1, which comprises a step of subjecting a plurality of the cell constructs according to claim 1 to fusion.

12. The cell construct according to claim 1, wherein the cells are uniformly distributed by three-dimensionally arranging the bio-compatible polymer blocks and cells.

13. the cell construct according to claim 1, wherein the cells are mesenchymal stem cells, cardiac muscle cells or vascular endothelial cells.