Method of inducing beta cells from urine-derived cells using small molecules

A method of producing induced endoderm cells from urine-derived cells, the method comprising:

• (a) providing urine-derived cells;
• wherein the urine-derived cells express human nuclear antigen, CD13, vimentin and E-cadherin and
• (b) inducing the urine-derived cells provided in step (a) to obtain induced endoderm cells by an induction process consisting of culturing said urine-derived cells in a primary induction culture medium comprising an effective amount of a combination of small molecule reprogramming factor(s) comprising a definitive endoderm inducer, a glycogen synthase kinase 3 (GSK3) inhibitor and Vitamin C for a first period of time;
• and
• wherein the method excludes the use of reprogramming factors that are not small molecules.

A method of producing induced pancreatic precursor cells from urine-derived cells, the method comprising:

• (a) providing urine-derived cells;
• wherein the urine-derived cells express human nuclear antigen, CD13, vimentin and E-cadherin
• (b) inducing the urine-derived cells provided in step (a) to obtain induced endoderm cells by an induction process consisting of culturing said urine-derived cells in a primary induction culture medium comprising an effective amount of a combination of small molecule reprogramming factor(s) comprising a definitive endoderm inducer, a glycogen synthase kinase 3 (GSK3) inhibitor and Vitamin C for a first period of time to obtain induced endoderm cells;
• and
• (c) inducing the induced endoderm cells obtained in step (b) by culturing said induced endoderm cells in a secondary induction culture medium comprising an effective amount of at least one small molecule reprogramming factor(s) selected from the group consisting of a PKC activator, a sonic hedgehog (SSH) inhibitor, a retinoic acid receptor (RAR) agonist, Vitamin C, an activin receptor-like kinase (ALK) receptor inhibitor, a Pdx1 inducer and a bone morphogenetic protein (BMP) inhibitor for a second period of time to obtain induced pancreatic precursor cells;
• and
• wherein the method excludes the use of reprogramming factors that are not small molecules.