A new shortened protocol to obtain islet-like cells from hESC-derived ductal cells
Por:
Vakilian, M, Hmadcha, A, Soria, B and Ghaedi, K
Publicada:
1 jul 2021
Ahead of Print:
1 jul 2021
Resumen:
Conventional methods for obtaining pancreatic beta cells are based on simulating the embryonic development phase of endocrine cells via hierarchical differentiation of pluripotent stem cells (PSCs). Accordingly, we attempted to modify the protocols for obtaining insulin-secreting cells (ISCs) by sequential differentiation of a human embryonic stem cell (hESC), using the HS181 cell line. Furthermore, we hypothesize that actual pancreatic endocrine cells may arise from trans-differentiation of mature ductal cells after the embryonic developmental stage and throughout the rest of life. According to the hypothesis, ductal cells are trans-differentiated into endocrine and exocrine cells, undergoing a partial epithelial to mesenchymal transition (EMT). To address this issue, we developed two new protocols based on hESC differentiation to obtain ductal cells and then induce EMT in cells to obtain hormone-secreting islet-like cells (HSCs). The ductal (pre-EMT exocrine) cells were then induced to undergo partial EMT by treating with Wnt3a and activin A, in hypoxia. The cell derived from the latter method significantly expressed the main endocrine cell-specific markers and also beta cells, in particular. These experiments not only support our hypothetical model but also offer a promising approach to develop new methods to compensate beta cell depletion in patients with type 1 diabetes mellitus (T1DM). Although this protocol of generating islet-like cells from ductal cells has a potential to treat T1DM, this strategy may be exploited to optimize the function of these cells in an animal model and future clinical applications.
Filiaciones:
Vakilian, M:
Pablo de Olavide Univ, Andalusian Ctr Mol Biol & Regenerat Med CABIMER, CSIC, Seville, Spain
Univ Malaga UMA, Inst Biomed Res Malaga IBIMA, Dept Cell Biol Genet & Physiol, Malaga, Spain
:
Pablo de Olavide Univ, Andalusian Ctr Mol Biol & Regenerat Med CABIMER, CSIC, Seville, Spain
Univ Alicante, Dept Biotechnol, Alicante, Spain
Univ Pablo de Olavide, Seville, Spain
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid, Spain
:
Pablo de Olavide Univ, Andalusian Ctr Mol Biol & Regenerat Med CABIMER, CSIC, Seville, Spain
Univ Pablo de Olavide, Seville, Spain
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid, Spain
Univ Miguel Hernandez de Elche, Sch Med, Inst Bioengn, Alicante, Spain
Ghaedi, K:
Univ Isfahan, Fac Biol Sci & Technol, Dept Cell & Mol Biol & Microbiol, Hezar Jerib Ave,Azadi Sq, Esfahan, Iran
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