Tissue-engineered three-dimensional model for tumor analysis

Abstract

A 3D decellularized bone scaffold seeded with cancer cells, such as prostate cancer cells or Ewing's sarcoma is provided. The three-dimensional includes Ewing's sarcoma (ES) tumor cells; and an engineered human bone scaffold. The engineered human bone scaffold further includes osteoblasts that secrete substance of the human bone, and osteoclasts that absorb bone tissue during growth and healing. The engineered human bone scaffold includes the tissue engineered three-dimensional model which recapitulates the osteolytic process. The engineered human bone scaffold is engineered by co-culturing of osteoblasts and osteoclasts. The osteoblast is produced by cell differentiation process from mesenchymal stem cells. The osteoclast is produced by cell differentiation from human monocytes, wherein the human monocytes are isolated from buffy coats. The scaffold can be used with cancer cell lines to identify therapeutic targets to slow, stop, and reverse tumor growth and progression as well as to predict the efficacy of potential therapeutics.

1 - 20 . (canceled) 
     
     
         21 . A tissue-engineered three-dimensional bone in vitro, comprising:
 a tissue-engineered bone microstructure containing mature osteoclasts and mature osteoblasts.   
     
     
         22 . The tissue engineered three-dimensional bone in vitro of  claim 21 , wherein the osteoclasts are metabolically active. 
     
     
         23 . The tissue engineered three-dimensional bone in vitro of  claim 21 , wherein the tissue-engineered microstructure exhibits a bone volume density of about 0.6 to 0.8 mm 3 . 
     
     
         24 . The tissue engineered three-dimensional bone in vitro of  claim 21 , wherein the tissue-engineered microstructure exhibits a balance between bone production and bone resorption. 
     
     
         25 . The tissue engineered three-dimensional bone in vitro of  claim 21 , wherein the tissue-engineered microstructure exhibits a connectivity density of about 10 to about 15 Conn. D 1/mm 3 ). 
     
     
         26 . The tissue engineered three-dimensional bone in vitro of  claim 21 , wherein the microstructure includes mosaic-patterned patches of bone marker. 
     
     
         27 . The tissue engineered three-dimensional bone in vitro of  claim 26 , wherein the bone marker is BSP. 
     
     
         28 . The tissue engineered three-dimensional bone in vitro of  claim 25 , wherein the bone microstructure includes visible resorption lacunae. 
     
     
         29 . The tissue engineered three-dimensional bone in vitro of  claim 21 , wherein the osteoblasts are metabolically active. 
     
     
         30 . The tissue engineered three-dimensional bone in vitro of  claim 21 , wherein microstructure is a tumor model. 
     
     
         31 . The tumor model of  claim 30 , wherein the tumor model is infused with Ewings sarcoma cells. 
     
     
         32 . The tumor model of  claim 30 , wherein the tumor model is infused with prostate cancer cells. 
     
     
         33 . A tissue-engineered three-dimensional bone tumor model, comprising
 a tissue engineered construct containing Ewings Sarcoma aggregates, mature osteoclasts, and mature osteoblasts, wherein the construct has a trabecular number.   
     
     
         34 . The tissue-engineered three-dimensional bone tumor model of  claim 33 , wherein the cancer tumor model exhibits a decrease in trabecular number. 
     
     
         35 . The tissue-engineered three-dimensional bone tumor model of  claim 33 , wherein the model mimics an osteolytic process observed in a patient. 
     
     
         36 . The tissue-engineered three-dimensional bone tumor model of  claim 33 , wherein the tissue-engineered three-dimensional bone tumor model mimics the biological and mechanical properties of Ewings Sarcoma. 
     
     
         37 . The tissue-engineered three-dimensional bone tumor model of  claim 33 , wherein the model includes a biomimetic environment for the Ewing's sarcoma tumor cell growth. 
     
     
         38 . The tissue-engineered three-dimensional bone tumor model of  claim 33 , wherein the ES cells, mature osteoblasts and mature osteoblasts are patient-derived cells. 
     
     
         39 . The tissue-engineered three-dimensional bone tumor model of  claim 38 , wherein the model is predictive of the patient's response to a drug. 
     
     
         40 . A tissue-engineered three-dimensional bone tumor model, comprising
 a tissue engineered construct containing Ewing's Sarcoma aggregates, mature osteoclasts, and mature osteoblasts,   wherein the tumor model forms avascular aggregates that increase in size over time, mimicking the initiation of native tumor formation.