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2017 ; 9
(3
): 457-63
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Beta-cell replacement strategies for diabetes
#MMPMID28984038
Kieffer TJ
; Woltjen K
; Osafune K
; Yabe D
; Inagaki N
J Diabetes Investig
2017[Oct]; 9
(3
): 457-63
PMID28984038
show ga
Diabetes is characterized by elevated levels of blood glucose as a result of
insufficient production of insulin from loss or dysfunction of pancreatic islet
?-cells. Here, we review several approaches to replacing ?-cells that were
recently discussed at a symposium held in Kyoto, Japan. Transplant of donor human
islets can effectively treat diabetes and eliminate the need for insulin
injections, supporting research aimed at identifying abundant supplies of cells.
Studies showing the feasibility of producing mouse islets in rats support the
concept of generating pigs with human pancreas that can serve as donors of human
islets, although scientific and ethical challenges remain. Alternatively, in
vitro differentiation of both human embryonic stem cells and induced pluripotent
stem cells is being actively pursued as an islet cell source, and embryonic stem
cell-derived pancreatic progenitor cells are now in clinical trials in North
America in patients with diabetes. Macro-encapsulation devices are being used to
contain and protect the cells from immune attack, and alternate strategies of
immune-isolation are being pursued, such as islets contained within long
microfibers. Recent advancements in genetic engineering tools offer exciting
opportunities to broaden therapeutic strategies and to probe the genetic
involvement in ?-cell failure that contributes to diabetes. Personalized medicine
might eventually become a possibility with genetically edited patient-induced
pluripotent stem cells, and the development of simplified robust differentiation
protocols that ideally become standardized and automated. Additional efforts to
develop a safe and effective ?-cell replacement strategy to treat diabetes are
warranted.