The use of stem cells in cell therapies has shown promising results in the treatment of several diseases,
including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various
locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In
vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell
lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for
which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in
IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of
the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to
complete differentiation. However, although there is no “gold standard” differentiation medium composition, most
prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and
glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is
to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation
techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.
