Soft tissue repair and regeneration using postpartum-derived cells and cell products

Patent metadata

Field	Value
Publication number	US-9504719-B2
Application number	US-31610405-A
Country	US
Kind code	B2
Filing date	Dec 22, 2005
Priority date	Jun 27, 2003
Publication date	Nov 29, 2016
Grant date	Nov 29, 2016

Abstract

Cells derived from postpartum tissue and products thereof having the potential to support cells of and/or differentiate to cells of a soft tissue lineage, and methods of preparation and use of those postpartum tissue-derived cells, are provided by the invention. The invention also provides methods for the use of such postpartum-derived cells and products related thereto in therapies for conditions of soft tissue.

First claim

What is claimed:

1. A method of making a cell lysate comprising lysing cells of a homogeneous umbilical cord cell population isolated from human umbilical cord tissue substantially free of blood, wherein said cell population self-renews and expands in culture, provides trophic support to a soft tissue cell, and has the following characteristics:
a) secretes MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO, MIP1b, RANTES, and TIMP1;
b) production of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A,B,C;
c) lacks production of CD31, CD34, CD45, CD80, CD86, CD 117, CD141, CD178, B7-H2, HLA-G, and HLA-DR,DP,DQ;
d) has increased expression, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell, of interleukin 8, reticulon 1 and chemokine (C-X-C motif) ligand 3; and
e) has the ability to undergo at least 40 population doublings in culture,
wherein a cell lysate is produced.

2. The method of claim 1 further comprising adding one or more bioactive factors.

3. The method of claim 2 wherein said bioactive factor is at least one of a differentiation-inducing factor, an anti-apoptotic agent, an anti-inflammatory agent, an immunosupressive/immunomodulatory agent, an anti-proliferative agent, a corticosteroid, an antibody, an anti-thrombogenic agent, an anti-oxidant, and scar inhibitory factor.

4. The method of claim 1 , further comprising adding a pharmaceutically acceptable carrier.

5. The method of claim 1 , wherein said cell population lacks secretion of SDF-1alpha, TGF-beta2, ANG2, PDGFbb, MIP1a, and VEGF.

6. The method of claim 1 , further comprising lyophilizing the cell lysate.

7. The method of claim 1 , wherein the cell lysing comprises disrupting the cells using freeze-thaw disruption, osmotic disruption, mechanical disruption, ultrasonic disruption, enzymatic disruption or chemical disruption.

8. A method of making a lyophilized cell lysate comprising lysing cells of a homogeneous umbilical cord cell population isolated from human umbilical cord tissue substantially free of blood, wherein said cell population self-renews and expands in culture, provides trophic support to a soft tissue cell, and has the following characteristics:
a) secretes MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO, MIP1b, RANTES, and TIMP1;
b) production of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A,B,C;
c) lacks production of CD31, CD34, CD45, CD80, CD86, CD 117, CD141, CD178, B7-H2, HLA-G, and HLA-DR,DP,DQ;
d) has increased expression, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell, of interleukin 8, reticulon 1 and chemokine (C-X-C motif) ligand 3; and
e) has the ability to undergo at least 40 population doublings in culture
wherein a cell lysate is produced, and
lyophilizing the cell lysate.

9. The method of claim 8 , wherein said cell population lacks secretion of SDF-1alpha, TGF-beta2, ANG2, PDGFbb, MIP1a, and VEGF.

10. The method of claim 8 , wherein the lysate comprises HGF, FGF, IL-8, TIMP1 and BDNF.

11. The method of claim 10 , wherein the lysate further comprises ANG2, HB-EGF, KGF, PDGFbb, VEGF, IL-6, MCP1 TGFa, TIMP2, and HGH.

12. The method of claim 8 further comprising adding one or more bioactive factors.

13. The method of claim 12 , wherein said bioactive factor is at least one of a differentiation-inducing factor, an anti-apoptotic agent, an anti-inflammatory agent, an immunosupressive/immunomodulatory agent, an anti-proliferative agent, a corticosteroid, an antibody, an anti-thrombogenic agent, an anti-oxidant, and scar inhibitory factor.

14. A method of making a cell lysate matrix complex comprising lysing cells of a homogeneous umbilical cord cell population isolated from human umbilical cord tissue substantially free of blood, wherein said cell population self-renews and expands in culture, provides trophic support to a soft tissue cell, and has the following characteristics:
a) secretes MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO, MIP1b, RANTES, and TIMP1;
b) production of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A,B,C;
c) lacks production of CD31, CD34, CD45, CD80, CD86, CD117, CD141, CD178, B7-H2, HLA-G, and HLA-DR,DP,DQ;
d) has increased expression, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell, of interleukin 8, reticulon 1 and chemokine (C-X-C motif) ligand 3; and
e) has the ability to undergo at least 40 population doublings in culture;
wherein a cell lysate is formed, and
adding a matrix to the cell lysate to form a complex.

Assignees

• Brown Laura
• Harmon Alexander M
• Gosiewska Anna
• Depuy Synthes Products Inc

Inventors

• Brown Laura
• Harmon Alexander M
• Gosiewska Anna

Classifications

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title