Methods of inducing cell differentiation with placental extracts

Abstract

Disclosed are methods of preparing and using placentally-derived stem cells and compositions useful for the treatment of cancer. Said stem cells and compositions function through inducing a “guided differentiation” program in cancer cells, thereby reducing malignancy. Further extension of the invention pertains to augmenting ability of administered cells to induce differentiation through the co-administration of known differentiation inducing agents. Within the context of this disclosure, methods for inducing host responses to cancer are also described.

1 . A cell free extract capable of inducing differentiation in cancer cells, the cell free extract produced by the process comprising:
 a. extracting human placenta;   b. homogenizing said placenta at a neutral pH, resulting in a homogenate;   c. centrifuging said homogenate in order to free the supernatant of cellular debris; and   d. purifying differentiation associated molecular weight fractions.   
     
     
         2 . The cell free extract of  claim 1  wherein the differentiation-inducing fraction purified is of molecular weight of 10-10,000 Daltons. 
     
     
         3 . The cell free extract of  claim 1  wherein the differentiation-inducing fraction purified is of molecular weight of 300-3,000 Daltons. 
     
     
         4 . A method of stimulating an immune response to cancer cells by administration of the cell free extract of  claim 1 , together with an appropriate immunological adjuvant. 
     
     
         5 . A method of prophylactically treating a cancer patient by administration of the cell free extract of  claim 1  to a patient in need thereof. 
     
     
         6 . A method of inhibiting progression of a preneoplastic lesion to neoplasia by administration of the cell free extract of  claim 1 . 
     
     
         7 . A differentiation inducing composition, suitable for administration to a patient in need thereof, derived from placental tissue, the composition produced by the process comprising:
 a. extracting human placenta;   b. homogenizing said placenta at a neutral pH, resulting in a homogenate;   c. centrifuging said homogenate in order to free the supernatant of cellular debris;   d. purifying the cell free-debris through adsorption on a C-18 column; and   e. filter sterilizing said composition.   
     
     
         8 . The composition of  claim 7 , wherein the homogenized portion of the placenta consists substantially of chorionic tissue. 
     
     
         9 . The composition of  claim 7 , wherein a histone deacetylase inhibitor is added directly to the composition. 
     
     
         10 . A method of inducing differentiation and reprogramming of distal cancer lesions through an intratumoral administration of the composition described in  claim 7 . 
     
     
         11 . A method of substantially increasing efficacy of the composition of  claim 7  by administration in a liposomal complex. 
     
     
         12 . A method of treating a cancer, comprising:
 (a) providing the placental cell free extract of  claim 1 , wherein said placental cell free extract comprises a cell differentiation associated molecular weight fraction comprising a molecular weight of about 10-10,000 Daltons; and   (b) contacting said placental cell free extract with a cancer cell selected from the group consisting of a leukemia cell, a prostate cancer cell, and a lung cancer cell.   
     
     
         13 . A method of inducing differentiation of a tumor cell, comprising contacting a tumor cell with the placental cell free extract of  claim 1 . 
     
     
         14 . A method of inhibiting progression of a neoplasm, comprising providing the placental cell free extract of  claim 1  and contacting said neoplasm with said placental cell free extract. 
     
     
         15 . The cell free extract of  claim 1 , wherein the method occurs at a neutral pH. 
     
     
         16 . The cell free extract of  claim 7 , wherein the method occurs at a neutral pH. 
     
     
         17 . A method of treating a cancer, comprising:
 (a) providing the differentiation inducing composition of  claim 7 , wherein said differentiation inducing composition comprises a cell differentiation associated molecular weight fraction comprising a molecular weight of about 10-10,000 Daltons; and   (b) contacting said differentiation inducing composition with a cancer cell selected from the group consisting of a leukemia cell, a prostate cancer cell, and a lung cancer cell.   
     
     
         18 . A method of inducing differentiation of a tumor cell, comprising contacting a tumor cell with the placental cell free extract of  claim 7 . 
     
     
         19 . A method of inhibiting progression of a neoplasm, comprising providing the placental cell free extract of  claim 7  and contacting said neoplasm with said placental cell free extract. 
     
     
         20 . A method of inhibiting progression of a neoplasm, comprising:
 providing a placental cell free extract made by the process comprising:
 extracting human placenta; 
 homogenizing said placenta at a neutral pH, resulting in a homogenate; 
 centrifuging said homogenate in order to free the supernatant of cellular debris; and 
 purifying the placental cell free extract comprising a cell differentiation associated molecular weight fraction comprising a molecular weight of about 10-10,000 Daltons; and 
   contacting said placental cell free extract with a neoplastic cell selected from the group consisting of a leukemia cell, a prostate cancer cell, and a lung cancer cell.   
     
     
         21 . A method of inhibiting progression of a neoplasm, comprising:
 providing a differentiation inducing composition made by the process of:
 extracting human placenta; 
 homogenizing said placenta at a neutral pH, resulting in a homogenate; 
 centrifuging said homogenate in order to free the supernatant of cellular debris; 
 purifying the cell free-debris through adsorption on a C-18 column; and 
 filter sterilizing said composition to obtain a differentiation inducing composition comprising a cell differentiation associated molecular weight fraction comprising a molecular weight of about 10-10,000 Daltons; and 
   contacting said differentiation inducing composition with a neoplastic cell selected from the group consisting of a leukemia cell, a prostate cancer cell, and a lung cancer cell.