METHODS OF CANCER IMMUNOTHERAPY
Provided herein are methods of differentiating stem cells via modulating miR-124, and the differentiated cells thereby. Also provided herein are methods for the treatment of diseases using the differentiated cells.
1 . A method of treating a cancer in a subject in need thereof, comprising administering to the subject an effective amount of an isolated human pancreatic progenitor cell, wherein the isolated human pancreatic progenitor cell expresses insulin and betatrophin.
2 . The method of claim 1 , wherein the isolated pancreatic progenitor cell further expresses C-peptide.
3 . The method of claim 1 , wherein the isolated pancreatic progenitor cell further expresses Ngn3.
4 . The method of claim 1 , wherein the isolated pancreatic progenitor cell further expresses C-peptide and Ngn3.
5 . The method of claim 1 , wherein the differentiated cell is a progenitor cell.
6 . The method of claim 5 , wherein the differentiated cell is a pancreatic progenitor cell.
7 . The method of claim 1 , wherein the differentiated cell is a pluripotent stem cell.
8 . The method of claim 1 , wherein the differentiated cell is an endodermal, mesodermal, or ectodermal progenitor cell.
9 . The method of claim 1 , wherein the differentiated cell is a definitive endoderm progenitor cell.
10 . The method of claim 1 , wherein the differentiated cell is a pancreatic endoderm progenitor cell.
11 . The method of claim 1 , wherein the differentiated cell is a multipotent progenitor cell or an oligopotent progenitor cell.
12 . The method of claim 1 , wherein the differentiated cell is a monopotent, bipotent, or tripotent progenitor cell.
13 . The method of claim 1 , wherein the differentiated cell is an endocrine, exocrine, or duct progenitor cell.
14 . The method of claim 1 , wherein the differentiated cell is a beta-cell.
15 . The method of claim 1 , wherein the differentiated cell is an insulin-producing cell.
16 . The method of claim 1 , wherein the administering comprises injecting the isolated pancreatic progenitor cell to the human in need thereof.
17 . The method of claim 1 , wherein the administering comprises implanting the isolated pancreatic progenitor cell to the human in need thereof.
18 . The method of claim 1 , wherein the cancer comprises a pancreatic cancer.
19 . The method of claim 1 , wherein the cancer comprises a carcinoma.
20 . The method of claim 1 , wherein the carcinoma comprises an adenocarcinoma or a choriocarcinoma.
21 . An isolated progenitor cell that expresses betatrophin, betatrophin mRNA, C-peptide, insulin, or any combination thereof, wherein the isolated progenitor cell is differentiated from a mammalian trophoblast stem cell.
22 . An isolated pancreatic progenitor cell, wherein the isolated pancreatic progenitor cell expresses one or more transcription factors selected from the group consisting of Foxa2, Pdx1, Ngn3, Ptf1a, and Nkx6.1.
23 . A method of treating a disease in a mammal in a subject in need thereof, the method comprising administering to the subject an isolated progenitor cell.
24 . A method of screening a substance for use in the treatment of a disease, the method comprising:
a) contacting an isolated pancreatic progenitor cell with the substance; and
b) detecting a change in the level of at least one transcript or protein in the isolated pancreatic progenitor cell.
25 . A method of screening a substance for cellular modulation or cellular toxicity of a cell, the method comprising:
a) contacting an isolated pancreatic progenitor cell with the substance;
b) determining a phenotypic or metabolic change in the isolated pancreatic progenitor cell that results from contact with the substance; and
c) correlating the change with cellular modulation.
26 . A method of producing insulin, betatrophin protein, or betatrophin mRNA, the method comprising contacting a mammalian trophoblast stem cell with one or more agents to activate miR-124, thereby producing a progenitor cell that secretes insulin in response to glucose stimulation or producing a progenitor cell that produces betatrophin protein or betatrophin mRNA.