The International Journal of Developmental Biology

Int. J. Dev. Biol. 56: 313 - 323 (2012)

Vol 56, Issue 5

Induction of differentiation of undifferentiated cells into pancreatic beta cells in vertebrates

Open Access | Review | Published: 25 May 2012

Masaki Hosoya*,1, Yuya Kunisada1, Akira Kurisaki2 and Makoto Asashima*,2

1Advanced Science Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa and 2Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan


The beta cells of the pancreatic islets, which maintain glucose homeostasis by secreting insulin, are important cells for sustaining life. In recent years, islet transplantation has been performed as a treatment for type I diabetes. Since there are not enough donors for patients awaiting transplantation, beta cells grown in vitro are expected to be utilized as a substitute for islets. To obtain the cells with properties of human beta cells, it is necessary to understand the process by which human pancreatic islets are formed, as well as their structural characteristics. By using undifferentiated cells, such as Xenopus laevis animal caps and mouse ES cells, pancreatic tissue has shown to be able to be induced in vitro. Various attempts have been made to obtain human beta cells from human ES/iPS cells. Versatile methods have been developed and improved efficiency has been achieved by the use of low molecular weight compounds, but the challenge remains to prevent tumor formation and achieve functional maturation. Inducing the differentiation of somatic stem cells into insulin-producing cells has also brought us closer to clinical application. There are still many challenges related to the practical use of beta cells derived from undifferentiated cells, such as the development of methods to substitute these cells for host beta cells, standardization of the treatment protocol, quality control, and confirmation of safety. Research on the methods of inducing undifferentiated cells to differentiate into beta cells has shown definite progress, suggesting that cell therapy for diabetes may become a preferred therapeutic option over islet transplantation.


undifferentiated cell, pancreatic b-cell, insulin, diabetes, transplantation

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