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This is because delivery of exogenous insulin coupled with glucose monitoring cannot provide the fine level of glucose control normally provided by endogenous \u03b2-cells in the context of intact islets. Moreover, a subset of people with diabetes lack awareness of hypoglycemic events; a status that can have grave consequences. Therefore, much effort has been focused on replacing lost or dysfunctional \u03b2-cells with cells derived from other sources. The advent of stem cell biology and cellular reprogramming strategies have provided impetus to this work and raised hopes that a \u03b2-cell replacement therapy is on the horizon. In this review, we look at two components that will be required for successful \u03b2-cell replacement therapy: a reliable and safe source of \u03b2-cells and a mechanism by which such cells can be delivered and protected from host immune destruction. Particular attention is paid to insulin-producing cells derived from pluripotent stem cells because this platform addresses the issue of scale, one of the more significant hurdles associated with potential cell-based therapies. We also review methods for encapsulating transplanted cells, a technique that allows grafts to evade immune attack and survive for a long term in the absence of ongoing immunosuppression. In surveying the literature, we conclude that there are still several substantial hurdles that need to be cleared before a stem cell-based \u03b2-cell replacement therapy for diabetes becomes a reality.<\/jats:p>","DOI":"10.1530\/jme-14-0188","type":"journal-article","created":{"date-parts":[[2014,11,10]],"date-time":"2014-11-10T23:28:42Z","timestamp":1415662122000},"page":"R119-R129","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":7,"title":["\u03b2-cell regeneration and differentiation: how close are we to the \u2018holy grail\u2019?"],"prefix":"10.1530","volume":"53","author":[{"given":"Gemma","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G","family":"Elefanty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard 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