Implantation of cell-matrix structure adjacent mesentery, omentum or peritoneum tissue

• US 5,804,178 A
• Filed: 02/28/1994
• Issued: 09/08/1998
• Est. Priority Date: 11/20/1986
• Status: Expired due to Term

• Current Assignee: Children's Medical Center Corporation, Massachusetts Institute of Technology
• Original Assignee: Children's Medical Center Corporation, Massachusetts Institute of Technology
• Inventors: Johnson, Lynt, Langer, Robert S., Vacanti, Joseph P.
• Primary Examiner(s): Naff, David M.
• Application Number:
  US08/203,509
• Time in Patent Office: 1,653 Days
• Field of Search: 435/177, 435/178, 435/180, 435/182, 435/181, 435/240.1, 435/240.23, 435/240, 435/242, 435/243, 435/395, 435/398, 435/402, 424/93.7, 424/422, 424/423, 424/426, 424/486, 424/548, 424/549, 436/823, 524/24, 525/421, 623/11, 623/12, 623/13
• US Class Current: 424/93.7
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3843 Connective tissue
• CPC Class Codes: A61L 27/3869 Epithelial tissues other than skin
• CPC Class Codes: C12N 2501/18 Liver cell growth factor (LCGF, Gly-His-Lys)
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

A matrix structure containing attached cells such as endocrine cells, fibroblasts, endothelial cells or genitourinary cells is implanted in a patient adjacent tissue having a high surface area and vasculature such as mesentery, omentum or peritoneum tissue. Large volumes of cells can be attached to the matrix and the matrix implanted with minimum trauma and blood loss into a patient to produce a functional organ equivalent. Multiple matrix structures containing cells can be implanted to functionally resemble naturally occurring organs. Implanting multiple matrices between folds of the mesentery is particularly well suited for growth of endocrine structures, including liver, pancreas, and adrenal gland. The matrix structure is preferably formed from a biodegradable artificial polymer. Collagen and non-biodegradable materials can also be used, and the matrix structure can be overlaid with a material that enhances cell attachment. Materials such as angiogenesis factors can be incorporated into a matrix and implanted prior to implanting the matrix containing cells or the materials can be incorporated into the matrix containing cells. Cells attached to the matrix may be cultured in vitro prior to implanting. Matrix structures containing different types of cells can be implanted juxtapositioned with each other.

Claims

1. A method of implanting a matrix structure having cells attached thereto comprising

a) providing a biocompatible polymeric matrix structure having attached thereto viable animal cells exhibiting normal growth and proliferation selected from the group consisting of endocrine cells, fibroblasts, endothelial cells, and genitourinary cells, which are allowed to attach thereto;

and

b) implanting the matrix structure having cells attached thereto into a patient in need thereof, wherein the matrix structure is juxtaposed with tissue having high surface area and vasculature;

adjacent the surface of the tissue selected from the group consisting of mesentery, omentum and peritoneum, and wherein the matrix structure is configured to allow adequate nutrients and gas exchange between the attached cells and the blood for the cells to remain viable and to form tissue.

2. The method of claim 1 wherein the tissue is the mesentery.

3. The method of claim 1 wherein the tissue is the omentum.

4. The method of claim 1 wherein the tissue is the peritoneum.

5. The method of claim 1 wherein the matrix is formed of a polymer selected from the group consisting of polylactic acid, polyglycolic acid, polyorthoester, polyanhydride, and combinations thereof.

6. The method of claim 1 wherein the cells are endocrine cells selected from the group consisting of hepatocytes, pancreatic cells, and adrenal cells.

7. The method of claim 1 further comprising incorporating into the matrix structure a compound selected from the group consisting of angiogenic compounds, protein growth factors, and immunomodulators.

8. The method of claim 1 comprising implanting prior to implantation of the matrix structure with attached cells a matrix containing a compound selected from the group consisting of angiogenic compounds, protein growth factors, and immunomodulators.

9. The method of claim 1 comprising culturing the viable cells attached to the polymeric matrix structure in vitro prior to implanting the matrix structure having cells attached thereto in vivo.

10. The method of claim 1 further comprising introducing a gene into the cells prior to attachment to the matrix structure to alter expression of a gene encoding a protein.

11. The method of claim 1 wherein multiple matrix structures having cells attached thereto are implanted which functionally resemble naturally occurring organs.

12. The method of claim 11 wherein matrix structures with one type of cell attached thereon are implanted in juxtaposition with matrix structures having other types of cells attached thereon.

13. The method of claim 1 wherein the matrix structure is formed of collagen.

14. The method of claim 1 wherein the matrix structure is formed of a non-biodegradable, biocompatible polymer.