# US 2013/0156847 A1 · Methods of inducing cell differentiation with placental extracts > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0156847 A1 - Document ID: US20130156847A1 - Status: Published application - Kind: A1 - Application number: 13/688,864 - Filed: 2012-11-29 - Published: 2013-06-20 - Earliest claimed: 2005-07-14 - Assignees: Medistem, Inc. - Inventors: Thomas E. Ichim - Web page: https://patentgrep.com/patent/US20130156847A1 ## CPC - A61K 35/50: Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells - A61K 35/44: Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells - A61P 35/00: Antineoplastic agents - A61P 35/04: specific for metastasis - C12N 5/0605: {Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly} - C12N 5/0694: {Cells of blood, e.g. leukemia cells, myeloma cells} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## 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. ## Claims ### Claim 1 A method of producing a cell free extract capable of inducing differentiation in cancer cells, 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, wherein the differentiation-inducing fraction purified is of molecular weight of 10-10,000 Daltons. ### Claim 2 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. ### Claim 3 (depends on 2) The cell free extract of claim 2 wherein the differentiation-inducing fraction purified is of molecular weight of 10-10,000 Daltons. ### Claim 4 (depends on 2) The cell free extract of claim 2 wherein the differentiation-inducing fraction purified is of molecular weight of 300-3,000 Daltons. ### Claim 5 (depends on 2) A method of stimulating an immune response to cancer cells by administration of the cell free extract of claim 2, together with an appropriate immunological adjuvant. ### Claim 6 (depends on 2) A method of prophylactically treating a cancer patient by administration of the cell free extract of claim 2 to a patient in need thereof. ### Claim 7 (depends on 2) A method of inhibiting progression of a preneoplastic lesion to neoplasia by administration of the cell free extract of claim 2. ### Claim 8 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. ### Claim 9 (depends on 8) The composition of claim 8, wherein the homogenized portion of the placenta consists substantially of chorionic tissue. ### Claim 10 (depends on 8) The composition of claim 8, wherein a histone deacetylase inhibitor is added directly to the composition. ### Claim 11 (depends on 7) A method of inducing differentiation and reprogramming of distal cancer lesions through an intratumoral administration of the composition described in claim 7. ### Claim 12 (depends on 7) A method of substantially increasing efficacy of the composition of claim 7 by administration in a liposomal complex. ### Claim 13 (depends on 2) A method of treating a cancer, comprising: (a) providing the placental cell free extract of claim 2, 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. ### Claim 14 (depends on 2) A method of inducing differentiation of a tumor cell, comprising contacting a tumor cell with the placental cell free extract of claim 2. ### Claim 15 (depends on 1) 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. ### Claim 16 (depends on 2) The cell free extract of claim 2, wherein the method occurs at a neutral pH. ### Claim 17 (depends on 8) The cell free extract of claim 8, wherein the method occurs at a neutral pH. ### Claim 18 (depends on 8) A method of treating a cancer, comprising: (a) providing the differentiation inducing composition of claim 8, 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. ### Claim 19 (depends on 8) A method of inducing differentiation of a tumor cell, comprising contacting a tumor cell with the placental cell free extract of claim 8. ### Claim 20 (depends on 8) A method of inhibiting progression of a neoplasm, comprising providing the placental cell free extract of claim 8 and contacting said neoplasm with said placental cell free extract. ### Claim 21 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. ### Claim 22 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.