US2014065108A1PendingUtilityA1

Tendon Stem Cells

43
Assignee: US HEALTHPriority: Jun 14, 2007Filed: Aug 29, 2013Published: Mar 6, 2014
Est. expiryJun 14, 2027(~0.9 yrs left)· nominal 20-yr term from priority
Inventors:Marian F. YoungYanming BiSongtao Shi
A61P 9/00A61P 29/00C12N 5/0662A61P 19/02A61P 19/08A61P 21/00A61P 19/00A61P 19/04A61P 17/02C12N 5/0668A61K 38/39A61K 35/32A61P 17/00C12N 5/066
43
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Claims

Abstract

The invention relates to tendon stem cells useful for treating a variety of diseases and condition, including tendon repair and attachment of tendon to bone. The invention is also directed to treatment and/or inhibition of bone formation by use of biglycan and/or fibromodulin.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A composition comprising an isolated tendon stem cell or cells. 
     
     
         2 . The composition of  claim 1 , wherein said composition comprises an enriched population of isolated stem cells, wherein the stem cells are enriched from an extracellular matrix niche within tendon tissue, and can give rise to progeny consisting of two or more tissue types, wherein at least one of the tissue types is tendon. 
     
     
         3 . The composition of  claim 1 , wherein said composition comprises an isolated non-embryonic stem cell that can differentiate into tendon tissue in vivo. 
     
     
         4 . The composition of  claim 1 , wherein the stem cell(s) are adult stem cells. 
     
     
         5 . The composition of  claim 1 , wherein the stem cell(s) are isolated from tendon tissue. 
     
     
         6 . The composition of  claim 1 , wherein the stem cell(s) are isolated from the tendon tissue extracellular matrix. 
     
     
         7 . The composition of  claim 1 , wherein the stem cell(s) remain undifferentiated in culture. 
     
     
         8 . The composition of  claim 1 , wherein the stem cell(s) differentiate into tendon tissue or tendon cells when in contact with extracellular matrix components in vivo. 
     
     
         9 . The composition of  claim 1 , wherein the stem cell(s) differentiate into tendon tissue or tendon cells in vitro. 
     
     
         10 . The composition of  claim 9 , wherein the tendon tissue can attach to bone. 
     
     
         11 . The composition of  claim 1 , wherein the stem cell(s) can differentiate into ligament. 
     
     
         12 . The composition of  claim 1 , wherein the stem cell(s) can differentiate into bone-producing cells. 
     
     
         13 . The composition of  claim 1 , wherein the stem cell(s) differentiate into bone-producing cells when exposed to bone morphogenetic protein 2 (BMP2). 
     
     
         14 . The composition of  claim 1 , wherein the stem cell(s) can give rise to osteogenesis, adipogenesis, chondrogenesis, or any combination thereof in a mammal. 
     
     
         15 . The composition of  claim 1 , wherein the stem cell(s) express higher levels of scleraxis, tenomodulin, and/or tenascin C than bone marrow stromal cells. 
     
     
         16 . The composition of  claim 1 , wherein the stem cell(s) express insignificant/minimal levels of CD34 (a hematopoietic stem cell marker), CD 117 (a hematopoietic stem cell marker), CD45 (a leukocyte marker), c-kit (an endothelial cell marker), CD106 (an endothelial cell marker), CD 18 (bone marrow stromal cell marker), and/or any combination thereof. 
     
     
         17 . The composition of  claim 1 , wherein the stem cell(s) express Stro-1, CD146 (Muc18), CD90, CD44, and/or any combination thereof. 
     
     
         18 . The composition of  claim 1 , wherein the stem cell(s) express stem cell antigen-1 (Sca-1). 
     
     
         19 . A differentiated progeny cell obtained from the composition of  claim 1 , wherein the progeny cell is an osteoblast, odontoblast, dentin-producing cell, chondrocyte, tendon cell, ligament cell, cartilage-forming cell, adipocyte, fibroblast, bone-producing cell, or a combination thereof. 
     
     
         20 . A composition comprising a carrier and the composition of  claim 1 . 
     
     
         21 . The composition of  claim 20 , further comprising an effective amount of biglycan and/or fibromodulin. 
     
     
         22 . The composition of  claim 21 , wherein the effective amount allows expansion of the tendon stem cells while inhibiting differentiation of at least a portion of the tendon stem cells. 
     
     
         23 . The composition of  claim 20 , wherein the carrier comprises a culture medium. 
     
     
         24 . The composition of  claim 20 , wherein the carrier comprises a saline solution, a buffered saline solution, gelatin, polyvinyl sponges, collagen, hydroxyapatite/tricalcium phosphate, and/or extracellular matrix. 
     
     
         25 . A method of treating a defect in a patient comprising: expanding a culture of tendon stem cells in vitro to form cultured cells, collecting the cultured cells for introduction into the patient, and depositing the cultured cells at or near the defect in the patient, wherein the tendon stem cells comprise the composition of  claim 1 . 
     
     
         26 . The method of  claim 25 , wherein the tendon stem cell(s) are autologous to the patient. 
     
     
         27 . The method of  claim 25 , wherein the tendon stem cell(s) are isolated from a healthy tendon of the patient. 
     
     
         28 . The method of  claim 25 , wherein expanding the culture of tendon stem cell(s) comprises culturing the tendon stem cell(s) in a culture medium comprising biglycan and/or fibromodulin. 
     
     
         29 . The method of  claim 28 , wherein the biglycan and/or fibromodulin is effective to expand an autologous tendon stem cell population but inhibit differentiation of at least a portion of the autologous tendon stem cells. 
     
     
         30 . The method of  claim 25 , wherein the defect is a tendon condition or disease. 
     
     
         31 . The method of  claim 30 , wherein the tendon condition or disease is an anterior cruciate ligament injury, tendonitis, tendon rupture, severed or torn tendon, Achille's tendonitis, torn or ruptured Achille's tendon, rotator cuff tendonitis, bursitis, retrocalcaneal bursitis, tenosynovitis, club foot, psoriatic arthritis, rheumatoid arthritis, jumpers knee, tendon injury arising from overuse or trauma, or a combination thereof. 
     
     
         32 . The method of  claim 25 , wherein the defect is chosen from the group consisting of skin laxness, skin thinning, hypertrophic scars, wound, burn, hernia, breast deficiency, ligament tear, muscle tear, a periodontal disorder, a periodontal disease, and sphincter structure deficiency. 
     
     
         33 . A method of generating bone-forming cells comprising treating the composition of  claim 20  with BMP-2 to thereby generate bone-forming cells. 
     
     
         34 . The method of  claim 33 , further comprising transplanting the bone-forming cells into a mammal. 
     
     
         35 . The method of  claim 33 , wherein the method is performed in vivo by administering the composition with the BMP-2 to a mammal. 
     
     
         36 . A method of treating undesired bone formation in a mammal comprising administering an effective amount of biglycan and/or fibromodulin to thereby treat undesired bone formation in the mammal. 
     
     
         37 . The method of  claim 36 , wherein the undesired bone formation is fibrodysplasia ossificans progressive. 
     
     
         38 . A method of expanding a population of tendon stem cells, the method comprising ex vivo culturing the tendon stem cells with an effective amount of biglycan and/or biglycan and fibromodulin, wherein the tendon stem cells are isolated from tendon of a mammal. 
     
     
         39 . A composition comprising a carrier and the differentiated progeny cell of  claim 19 . 
     
     
         40 . The composition of  claim 39 , further comprising an effective amount of biglycan and/or fibromodulin. 
     
     
         41 . The composition of  claim 40 , wherein the effective amount allows expansion of the tendon stem cells while inhibiting differentiation of at least a portion of the tendon stem cells. 
     
     
         42 . The composition of  claim 39 , wherein the carrier comprises a culture medium. 
     
     
         43 . The composition of  claim 39 , wherein the carrier comprises a saline solution, a buffered saline solution, gelatin, polyvinyl sponges, collagen, hydroxyapatite/tricalcium phosphate, and/or extracellular matrix. 
     
     
         44 . A method of generating bone-forming cells comprising treating the composition of  claim 39  with BMP-2 to thereby generate bone-forming cells. 
     
     
         45 . The method of  claim 44 , further comprising transplanting the bone-forming cells into a mammal. 
     
     
         46 . The method of  claim 44 , wherein the method is performed in vivo by administering the composition with the BMP-2 to a mammal.

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