题名：Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells.
作者：KUMAR A; LO NIGRO A; GYSEMANS C; CAI Q; ESGUERRA C; NELSON-HOLTE M; HEREMANS Y; JIMENEZ-GONZALEZ M; PORCIUNCULA A; MATHIEU C; BINAS B; HEIMBERG H; PROSPER F; HERING B; VERFAILLIE CM; BARAJAS M;
来源：PLoS One. 2013 May 9;8(5):e63491. doi: 10.1371/journal.pone.0063491. Print 2013. [ IF= 4.09 ] ]
摘要：beta-cell replacement may efficiently cure type 1 diabetic (T1D) patients whose
insulin-secreting beta-cells have been selectively destroyed by
autoantigen-reactive T cells. To generate insulin-secreting cells we used two
cell sources: rat multipotent adult progenitor cells (rMAPC) and the highly
similar rat extra-embryonic endoderm precursor (rXEN-P) cells isolated under
rMAPC conditions from blastocysts (rHypoSC). rMAPC/rHypoSC were sequentially
committed to definitive endoderm, pancreatic endoderm, and beta-cell like cells.
On day 21, 20% of rMAPC/rHypoSC progeny expressed Pdx1 and C-peptide.
rMAPCr/HypoSC progeny secreted C-peptide under the stimulus of insulin agonist
carbachol, and was inhibited by the L-type voltage-dependent calcium channel
blocker nifedipine. When rMAPC or rHypoSC differentiated d21 progeny were grafted
under the kidney capsule of streptozotocin-induced diabetic nude mice,
hyperglycemia reversed after 4 weeks in 6/10 rMAPC- and 5/10 rHypoSC-transplanted
mice. Hyperglycemia recurred within 24 hours of graft removal and the
histological analysis of the retrieved grafts revealed presence of Pdx1-, Nkx6.1-
and C-peptide-positive cells. The ability of both rMAPC and HypoSC to
differentiate to functional beta-cell like cells may serve to gain insight into
signals that govern beta-cell differentiation and aid in developing culture
systems to commit other (pluripotent) stem cells to clinically useful beta-cells
for cell therapy of T1D.