TREATMENT OF INTERVERTEBRAL DISC DEGENERATION USING HUMAN UMBILICAL CORD TISSUE-DERIVED CELLS
Methods for treating a patient having a disease or condition related to IVD degeneration are provided. The methods comprise administering cells obtained from human umbilical cord tissue, or administering pharmaceutical compositions comprising such cells or prepared from such cells and optionally a hydrogel. In some embodiments, administering the cells promotes repair and regeneration of degenerated IVD tissue in the patient. Pharmaceutical compositions for use in the inventive methods, as well as kits for practicing the methods are also provided.
1 . A method of treating a disease or condition related to intervertebral disc degeneration, comprising administering a pharmaceutical composition comprising a hydrogel and an isolated homogenous population of cells obtained from human umbilical cord tissue to an intervertebral disc in an amount effective to treat the disease or condition, wherein the umbilical cord tissue is substantially free of blood, and wherein the isolated homogenous population of cells is capable of self-renewal and expansion in culture, has the potential to differentiate and does not express CD117 or telomerase.
2 . The method of claim 1 wherein the isolated population of cells has one or more of the following characteristics:
(a) expresses reticulon, chemokine receptor ligand 3, and/or granulocyte chemotactic protein;
(b) does not produce CD31, CD34 and HLA-DR;
(c) expresses, relative to a human fibroblast, mesenchymal stem cell, or iliac crest bone marrow cell, increased levels of oxidized interleukin 8 and reticulon 1; and
(d) expresses CD10, CD13, CD44, CD73, and CD90.
3 . The method of claim 1 , wherein the pharmaceutical composition is administered by injection.
4 . The method of claim 1 , wherein the pharmaceutical composition further comprises at least one other cell type and/or at least one agent.
5 . The method of claim 4 , wherein the at least one agent is a trophic factor.
6 . The method of claim 5 , wherein the trophic fact is selected from the group consisting of TGF-beta, GDF-5, PDGF-BB and TIMP1.
7 . The method of claim 4 , wherein the at least one other cell type is engineered to express at least one exogenous gene product.
8 . The method of claim 4 , wherein the exogenous gene product is a trophic factor.
9 . The method of claim 1 , wherein the pharmaceutical composition is administered into a degenerated intervertebral disc.
10 . The method of claim 9 , wherein the pharmaceutical composition is administered into the nucleus pulposus or into the annulus fibrosus of the intervertebral disc.
11 . The method of claim 1 , further comprising inducing the isolated homogenous population of cells obtained from human umbilical cord tissue to at least partially differentiate in vitro.
12 . The method of claim 11 , wherein the isolated homogenous population of cells is induced to differentiate into cells displaying an annulus fibrosus cell phenotype.
13 . The method of claim 11 , wherein the isolated homogenous population of cells is induced to differentiate into cells displaying a nucleus pulposus cell phenotype.
14 . A method of treating a disease or condition related to intervertebral disc degeneration, comprising administering a hydrogel and an isolated homogenous population of cells obtained from human umbilical cord tissue to an intervertebral disc in an amount effective to treat the disease or condition, wherein the umbilical cord tissue is substantially free of blood, and wherein the isolated homogenous population of cells is capable of self-renewal and expansion in culture, has potential to differentiate and does not express CD117 or telomerase.
15 . The method of claim 14 , wherein the isolated population of cells has one or more of the following characteristics:
(a) expresses reticulon, chemokine receptor ligand 3 and granulocyte chemotactic protein;
(b) does not produce CD31, CD34 and HLA-DR;
(c) expresses, relative to a human fibroblast, mesenchymal stem cell, or iliac crest bone marrow cell, increased levels of interleukin 8 and reticulon 1; and
(d) expresses CD10, CD13, CD44, CD73, and CD90.
16 . The method of claim 14 , wherein the isolated homogenous population of cells and the hydrogel are administered by injection.
17 . The method of claim 14 , wherein hydrogel is administered simultaneously with, or before, or after, the isolated homogenous population of cells obtained from human umbilical cord tissue.
18 . The method of claim 14 , wherein the isolated homogenous population of cells is administered within an implantable device.
19 . The method of claim 14 , further comprising administration of at least one other cell type simultaneously with, or before, or after, the isolated homogenous population of cells obtained from human umbilical cord tissue.
20 . The method of claim 19 , wherein the at least one other cell type is engineered to express at least on exogenous gene product.
21 . The method of claim 20 , wherein the exogenous gene product is a trophic factor.
22 . The method of claim 21 , wherein the exogenous gene product modulates expression of one or more extracellular matrix proteins.
23 . The method of claim 14 further comprising administration of least one agent.
24 . The method of claim 23 , wherein the at least one agent is a trophic factor.
25 . The method of claim 24 , wherein the trophic factor is selected from the group consisting of TGF-beta, GDF-5, PDGF-BB and TIMP1.
26 . The method of claim 25 , wherein the trophic factor exerts a trophic effect on the isolated homogenous cell population obtained from human umbilical cord tissue.
27 . The method of claim 14 , wherein the isolated homogenous cell population and hydrogel are administered into a degenerated intervertebral disc.
28 . The method of claim 27 , wherein the isolated homogenous cell population and hydrogel are administered into the nucleus pulposus of the intervertebral disc.
29 . The method of claim 27 , wherein the isolated homogenous cell population and hydrogel are administered into the annulus fibrosus of the intervertebral disc.
30 . The method of claim 14 , further comprising inducing the isolated homogenous population of cells obtained from human umbilical cord tissue to at least partially differentiate in vitro.
31 . The method of claim 30 , wherein the isolated homogenous population of cells is induced to differentiate into cells displaying an annulus fibrosus cell phenotype.
32 . The method of claim 30 , wherein the isolated homogenous population of cells is induced to differentiate into cells displaying a nucleus pulposus cell phenotype.
33 . A method of treating a disease or condition related to intervertebral disc degeneration, comprising administering a hydrogel in an amount effective to treat the disease or condition.
34 . The method of claim 33 , wherein the hydrogel comprises fibrinogen and thrombin.
35 . The method of claim 33 , wherein the hydrogel comprises fibrin glue.