05684977

April 06, 2021, 19:13

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The review was very informative for a non-expert and recapitulated many aspects of interest, covering updated progress and additional challenges that need to be overcome. Section 1&2: Introduction/ Brief summary of autoimmunity in T1DM The authors should have merged the first two sections after the abstract. The review would flow better, if the second main section (Brief summary of autoiimunity in T1DM) came after the first paragraph of the first section (Introduction). Particularly, because the authors finish the former with the message of the Β islet destruction and in the second paragraph of th eintroduction they explain adequately how this challenge can be surpassed. Section 3: Defects of current T1DM treatment I think it would be interesting if the authors referenced in the second paragraph reviews on a) selection of encapsulation materials and transplantation site, b)improve immune regulation and c) blood vessel formation Moreover, since the following sections focus significantly on key transcription factors for stem cell differentiation, the authors could have made a more compelling case about their importance in this paragraph. ANother key point I would like to address is that I always find interesting the 'prevent autoimmune destruction' concept, since in many cases, the damage is irreversible at the time of diagnosis. Therefore, the authors should have addressed here, providing more literature, the two other options, which are induced regeneration from MSCs or their differentiation to Β-islet. Despite the focus on the latter in the following sections, if this contrast would have been explicitly explained and contrasted at this point, the readers would assimilate easier the greater image of the clinical bottlenecks of possible T1DM treatments. Section 4: Maturation process of Β cells in vivo This chapter feels a bit misleading from the title, since it mostly focuses on the islet development steps during the embryonic development, in mice or humans. Plus, many aspects of this paragraph are informative, yet do not correlate significantly with the follow-up section, of how the maturaiton actually occurs. Thus, most of the points raised in this paragraph can be overlooked and forgotten from the reader, thus weakening the overall view on the paper. The most relevant aspect described is the MAF transcription factor and a few others which are introduced later, however the major aspect of the chapter is very introductory and based on the paper title, could be reduced. Section 5: Key markers in the process of β-cell maturation This part was very detailed and elaborate, with lots of evidence and body of work done previously, which do not come by as superficial information. What could have made the whole paragraph to read, would have been to split it in at least two or three subsections, underlying a wider message across each, since it comprises of numeorus factors that affect β cell maturation Section 6: Induction of β cells in vitro and current problems This is also a very well-written paragraph touching upon many crucial prerequisites in testing methods to produce effectively β cells, such as prolonged and sustainable insulin release, autocrine regulation of Β cells by other pancreatic islet cell types, culture techniques based on nutrition, maturation, and TF delivery.

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