Therapeutic products comprising vitalized placental dispersions

Abstract

This invention provides a fluid therapeutic placental product comprising placental cells and a placental dispersion comprising placental factors. The placental cells and the placental dispersion are derived from placental tissue. A placental tissue can optionally be an amnion, chorion, or a trophoblast-depleted chorion. The placental product of the present invention is useful in treating a patient with a tissue injury (e.g. wound or burn) by applying the placental product to the injury. Similar application is useful with ligament and tendon repair and for engraftment procedures such as bone engraftment.

1 - 30 . (canceled) 
     
     
         31 . A therapeutic placental product comprising:
 a. placental cells in an amount at least about 10,000 per ml of placental product; and   b. placental factors comprising one or more extracellular matrix proteins, one or more protease inhibitors, one or more growth factors, one or more angiogenic factors, and one or more MMPs;   wherein the therapeutic placental product is a dispersion and wherein the placental factors are chorionic placental factors.   
     
     
         32 . The therapeutic placental product of  claim 31 , wherein the one or more extracellular matrix proteins comprise fibronectin, wherein the one or more protease inhibitors comprise a TIMP, wherein the one or more growth factors comprise a TGF, and wherein the one or more angiogenic factors comprise a bFGF. 
     
     
         33 . The therapeutic placental product of  claim 32 , wherein: the fibronectin is in a concentration of at least 740 ng/m of the placental product, the TIMP is in a total TIMP concentration of at least 6,500 pg/ml of the placental product, the TGF is TGFβ1 in a concentration of at least 260 pg/ml of the placental product, the bFGF is in a concentration of at least 900 pg/ml of the placental product, and the MMP is in a total MMP concentration of at least 13,000 pg/ml of the placental product. 
     
     
         34 . The therapeutic placental product of  claim 32 , wherein: the placental cells are in an amount of less than about 1,000,000 per ml of placental product, the fibronectin is in a concentration of at least 740 ng/m of the placental product and less than about 361,000 ng/ml of the placental product, the TIMP is in a total TIMP concentration of at least 6,500 pg/ml of the placental product and less than about 15,000 ng/ml of the placental product, the TGF comprises TGFβ1 in a concentration of at least 250 pg/ml of the placental product and less than about 26,000 pg/ml of the placental product, the bFGF is in a concentration of at least 900 pg/ml of the placental product and less than about 47,000 pg/ml of the placental product, and the MMP is in a total MMP concentration of at least 13,000 pg/ml of the placental product and less than about 1,000 ng/ml of the placental product. 
     
     
         35 . A therapeutic placental product comprising:
 a. placental cells in an amount of at least about 10,000 per ml of placental product; and   b. placental factors comprising one or more members of the group consisting of extracellular matrix proteins, protease inhibitors, growth factors, angiogenic factors, and MMPs,   wherein the placental product is a dispersion and wherein the placental factors are chorionic placental factors.   
     
     
         36 . The therapeutic placental product of  claim 35 , wherein the placental product comprises one or more protease inhibitors selected from the group consisting of matrix metalloproteinases (TIMPs), alpha-2 macroglobulin, and thrombospondins. 
     
     
         37 . A therapeutic placental product comprising:
 a. placental cells in at least about 10,000 per ml of placental product; and   b. placental factors comprising one or more members of the group consisting of fibronectins, TIMPs, TGFs, bFGF, and MMPs,   wherein the placental product is a dispersion and wherein the placental factors are chorionic placental factors.   
     
     
         38 . The therapeutic placental product of  claim 37 , wherein the placental factors comprise one or more members of the group consisting of fibronectins in a concentration of at least 740 ng/ml of the placental product, TIMPs in a total TIMP concentration of at least 6,500 pg/ml of the placental product, TGFβ1 in a concentration of at least 250 pg/ml of the placental product, bFGF in a concentration of at least 900 pg/ml of the placental product, and MMPs in a total MMP concentration of at least 13,000 pg/ml of the placental product. 
     
     
         39 . The therapeutic placental product of  claim 37 , wherein the placental factors further comprise two or more placental factors of the identity and in the range set forth in Table 1, Table 2, Table 3, or Table 5. 
     
     
         40 . The therapeutic placental product of  claim 38 , wherein the placental product comprises one or more angiogenic factors selected from the group consisting of VEGF and bFGF. 
     
     
         41 . The therapeutic placental product of  claim 38 , wherein the placental product comprises one or more factors which promote the migration of epithelial cells into a wound selected from the group consisting of HGF and KGF. 
     
     
         42 . The therapeutic placental product of  claim 37 , wherein the placental cells are selected from the group consisting of MSCs, ESCs, placenta-derived mesenchymal progenitor cells, placental mesenchymal stem cells, fibroblasts, epithelial cells, and placental mesenchymal cells. 
     
     
         43 . The therapeutic placental product of  claim 37 , wherein the placental cells are stromal cells. 
     
     
         44 . The therapeutic placental product of  claim 37 , wherein the placental dispersion is a homogenate. 
     
     
         45 . The therapeutic placental product of  claim 37 , wherein the placental cells are cryopreserved. 
     
     
         46 . The therapeutic placental product of  claim 37 , wherein the dispersion is cryopreserved. 
     
     
         47 . The therapeutic placental product of  claim 37 , wherein the placental factors are cryopreserved. 
     
     
         48 . The therapeutic placental product of  claim 31 , wherein:
 a. the placental product comprises HGF and KGF;   b. the placental cells comprise MSCs and cells selected from the group consisting of ESCs, placenta-derived mesenchymal progenitor cells, placental mesenchymal stem cells, fibroblasts, epithelial cells, and placental mesenchymal cells;   c. wherein the placental dispersion is a homogenate; and   d. wherein the placental cells are cryopreserved.   
     
     
         49 . A method of treating a tissue injury comprising administering to a subject in need thereof a therapeutic placental product of  claim 31 .