METHODS OF INDUCING CELL DIFFERENTIATION WITH PLACENTAL EXTRACTS
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.