# US 2013/0156744 A1 · Methods of recellularizing a tissue or organ for improved transplantability

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- Number: US 2013/0156744 A1
- Document ID: US20130156744A1
- Status: Published application
- Kind: A1
- Application number: 13/820,079
- Filed: 2011-09-01
- Published: 2013-06-20
- Earliest claimed: 2010-09-01
- Assignees: Regents of the University of Minnesota
- Inventors: Doris Taylor; Stefan M. Kren
- Web page: https://patentgrep.com/patent/US20130156744A1

## CPC

- C12N 5/0062: {General methods for three-dimensional culture}
- A61L 27/3604: {characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel}
- A61L 27/3808: {Endothelial cells}
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 5/069: {Vascular Endothelial cells}
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Described herein are methods of recellularizing an organ or tissue matrix.

## Claims

### Claim 1

An ex vivo method of recellularizing a tissue or organ matrix, comprising the steps of:
a) providing a tissue or organ matrix perfused with a physiological buffer under pressure; and
b) reendothelializing the tissue or organ matrix by perfusing the tissue or organ matrix with a physiological composition comprising a substantially pure population of endothelial cells or endothelial progenitor cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the endothelial cells are selected from the group consisting of blood endothelial cells, bone marrow endothelial cells, circulating endothelial cells, human aorta endothelial cells, human brain microvascular endothelial cells, human dermal microvascular endothelial cells, human intestinal microvascular endothelial cells, human lung microvascular endothelial cells, human microvascular endothelial cells, hepatic sinusoidal endothelial cells, human saphenous vein endothelial cells, human umbilical vein endothelial cells, lymphatic endothelial cells, microvessel endothelial cells, microvascular endothelial cells, pulmonary artery endothelial cells, retinal capillary endothelial cells, retinal microvascular endothelial cells, vascular endothelial cells, umbilical cord blood endothelial cells, liver sinusoidal endothelial cells, colony forming unit-endothelial cells (CFU-ECs), circulating angiogenic cells (CACs), circulating endothelial precursors (CEPs), endothelial colony-forming cells (ECFC), low proliferative potential ECFC (LPP-ECFC), high proliferative ECFC (HPP-ECFC), and combinations thereof.

### Claim 3 (depends on 1)

The method of claim 1 wherein the endothelial cells or endothelial progenitor cells are embryonic stem cells (ESCs)- or induced pluripotent stem cells (iPSCs)-derived endothelial cells or endothelial progenitor cells.

### Claim 4 (depends on 1)

The method of claim 1 wherein the tissue or organ matrix is a biological tissue or organ matrix.

### Claim 5 (depends on 4)

The method of claim 4, wherein the biological tissue or organ matrix originates from an organ selected from the group consisting of a heart, kidney, liver, lung, pancreas, intestine, muscle, skin, breast, esophagus, trachea, or omentum.

### Claim 6 (depends on 4)

The method of claim 4, wherein the biological tissue or organ matrix is a perfusion-decellularized tissue or organ matrix.

### Claim 7 (depends on 4)

The method of claim 4, wherein the biological tissue or organ matrix and the endothelial cells or endothelial precursor cells are xenogeneic.

### Claim 8 (depends on 4)

The method of claim 4, wherein the biological tissue or organ matrix and the endothelial cells or endothelial precursor cells are allogeneic.

### Claim 9 (depends on 1)

The method of claim 1 further comprising introducing cells other than endothelial or endothelial progenitor cells into or onto the tissue or organ matrix before step b).

### Claim 10 (depends on 1)

The method of claim 1 further comprising introducing cells other than endothelial or endothelial progenitor cells into or onto the tissue or organ matrix after step b).

### Claim 11

A method of reducing thrombogenesis and immunogenicity in a recellularized tissue or organ following transplantation into a recipient, comprising:
a) providing a tissue or organ matrix perfused with a physiological buffer under pressure;
b) reendothelializing the tissue or organ matrix by perfusing the tissue or organ matrix with a physiological composition comprising a substantially pure population of endothelial cells or endothelial progenitor cells; and
c) transplanting the reendothelialized tissue or organ matrix into the recipient.

### Claim 12 (depends on 11)

The method of claim 11, wherein the endothelial cells are selected from the group consisting of blood endothelial cells, bone marrow endothelial cells, circulating endothelial cells, human aorta endothelial cells, human brain microvascular endothelial cells, human dermal microvascular endothelial cells, human intestinal microvascular endothelial cells, human lung microvascular endothelial cells, human microvascular endothelial cells, hepatic sinusoidal endothelial cells, human saphenous vein endothelial cells, human umbilical vein endothelial cells, lymphatic endothelial cells, microvessel endothelial cells, microvascular endothelial cells, pulmonary artery endothelial cells, retinal capillary endothelial cells, retinal microvascular endothelial cells, vascular endothelial cells, umbilical cord blood endothelial cells, liver sinusoidal endothelial cells, colony forming unit-endothelial cells (CFU-ECs), circulating angiogenic cells (CACs), circulating endothelial precursors (CEPs), endothelial colony-forming cells (ECFC), low proliferative potential ECFC (LPP-ECFC), high proliferative ECFC (HPP-ECFC), and combinations thereof.

### Claim 13 (depends on 11)

The method of claim 11 wherein the endothelial cells or endothelial progenitor cells are embryonic stem cells (ESCs)- or induced pluripotent stem cells (iPSCs)-derived endothelial cells or endothelial progenitor cells.

### Claim 14 (depends on 11)

The method of claim 11 wherein the tissue or organ matrix is a biological tissue or organ matrix.

### Claim 15 (depends on 14)

The method of claim 14 wherein the biological tissue or organ matrix originates from an organ selected from the group consisting of a heart, kidney, liver, lung, pancreas, intestine, muscle, skin, breast, esophagus, trachea, or omentum.

### Claim 16 (depends on 14)

The method of claim 14, wherein the biological tissue or organ matrix is a perfusion-decellularized tissue or organ matrix.

### Claim 17 (depends on 14)

The method of claim 14, wherein the biological tissue or organ matrix and the endothelial cells or endothelial precursor cells are xenogeneic.

### Claim 18 (depends on 14)

The method of claim 14, wherein the biological tissue or organ matrix and the endothelial cells or endothelial precursor cells are allogeneic.

### Claim 19 (depends on 14)

The method of claim 14, wherein the biological tissue or organ matrix is xenogeneic to the recipient and wherein the endothelial cells or endothelial progenitor cells are allogeneic to the recipient.

### Claim 20 (depends on 11)

The method of claim 11 further comprising introducing cells other than endothelial or endothelial progenitor cells into or onto the tissue or organ matrix before step b).

### Claim 21 (depends on 11)

The method of claim 11 further comprising introducing cells other than endothelial or endothelial progenitor cells into or onto the tissue or organ matrix after step b).

### Claim 22 (depends on 11)

The method of claim 11 further comprising introducing cells other than endothelial cells or endothelial progenitor cells into or onto the tissue or organ matrix after step c).

### Claim 23 (depends on 20)

The method of claim 20 wherein the physiological composition comprising cells other than endothelial cells or endothelial progenitor cells is introduced to the tissue or organ matrix via perfusion, direct injection, topical application, or combinations thereof.

### Claim 24 (depends on 1)

The method of claim 1 wherein the provided tissue or organ matrix is perfusion decellularized.