Induction of Islet Cytodifferentiation by Fetal Mesenchyme in Adult Pancreatic Ductal Epithelium

Dudek, Ronald W.; Lawrence, Irvin E.; Hill, Ronald S.; Johnson, Robert C.

doi:10.2337/diab.40.8.1041

Cited by 80 publications

(49 citation statements)

References 15 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors postulated that the newly formed beta cells derived from precursor cells in the duct epithelium. Another study [5] transplanted adult rat pancreatic duct epithelium under the skin of nude mice, and found only insulin-positive cells in the vicinity of ducts that were implanted with fetal mesenchyme. While the appearance of insulin-positive cells in duct cell preparations is interesting, persistent caution will be needed to distinguish newly formed from initially "contaminating" endocrine cells; it is also not known whether the presence of duct cells can affect the survival and function of neighboring islets.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Formation of insulin-positive cells in implants of human pancreatic duct cell preparations from young donors

et al. 2003

View full text Add to dashboard Cite

Aims/hypothesis. Pancreatic ducts are considered as potential sites for neogenesis of beta cells. In vitro studies have reported formation of islets from postnatal human and rodent duct tissue. We examined whether postnatal human duct-cell preparations can generate new beta cells after transplantation. Methods. Pancreatic duct cells were prepared from the non-endocrine fraction of human donor pancreases that were processed for islet-cell isolation. Grafts containing 0.5 million duct cells with 1% contaminating insulin-positive cells were implanted under the kidney capsule of normoglycaemic nude mice. At 0.5 and 10 weeks post-transplantation, implants were examined for their cellular composition and for the volumes of their composing cell populations, i.e. cytokeratin 19-positive duct cells, synaptophysin-, insulin-and glucagon-positive endocrine cells. Results. Between week 0.5 and 10, duct-cell volume decreased by at least 90% whereas the change in insulin-positive cell volume depended on donor age. Implants from donors over10 years had a threefold decrease in their insulin-positive cell volume, while those from donors under 10 years had a 2.5-fold increase. After 10 weeks, the implants from the younger donors consisted of 19% insulin-positive cells occurring as single units or small cell clusters. Three percent of these insulin-positive cells also expressed the ductal marker CK 19 and were consistently found in conjunction with ductal epithelia; up to 1% was positive for the proliferation marker BrdU and located in small endocrine cell clusters. Conclusions/interpretation. These data indicate that duct cell preparations from donors under 10 years can generate insulin-positive cells. This process might involve differentiation of CK 19-positive-insulin cells that are formed at the duct epithelia as well as proliferation of insulin-positive cells within endocrine cell aggregates. [Diabetologia (2003) 46:830-838]

show abstract

Section: Discussionmentioning

confidence: 99%

“…New beta cells might be formed by differentiation from stem cells or precursor cells [1,2,3,4], by transdifferentiation of other pancreatic cell types [5,6,7,8,9] or by replication of beta cells [10,11,12]. These processes could occur within or outside the islets of Langerhans.…”

mentioning

confidence: 99%

Formation of insulin-positive cells in implants of human pancreatic duct cell preparations from young donors

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Since glucose transfers between fetuses and the maternal body through the placenta (Hay and Anderson, 2001), as shown in this experiment, B-cells damaged by STZ treatment do not increase the fetal plasma glucose concentration; thus, it is possible to maintain a constant condition without induction of hyperglycemia, which is beneficial for the elucidation of the B-cell neogenesis mechanism. There have been studies of the epithelial-mesenchymal interaction in the organogenesis of the pancreas (Wessels and Cohen, 1967;Pictet and Rutter, 1972;Dudek et al, 1991;Gittes et al, 1996) and Miralles et al (1998) demonstrated that the presence of the mesenchyme leads the primordial pancreas to the exocrine part and that this effect is produced by follistatin secreted from the mesenchyme. Of the cells that constitute the primordial pancreas, precursor cells with no sensitivity to follistatin are assumed to differentiate into endocrine cells, and growth factors derived from the mesenchyme or exocrine cells are considered to promote sustained expression of PDX-1.…”

Section: Discussionmentioning

confidence: 99%

Recovery in the fetal pancreatic islet following fetal administration of streptozotocin in the rat in vivo and in vitro

et al. 2004

View full text Add to dashboard Cite

In our previous study, after direct administration of streptozotocin (STZ; 400 g/g) to fetuses on day 19 of gestation, the B-cell volume in fetal pancreatic islets showed a marked decrease, but gradually recovered with electron microscopic confirmation of B-cell regeneration. However, STZ at this dose often caused fetal death. In this study, therefore, we determined whether B-cells are newly generated after treatment with STZ at a smaller dose in vivo and in vitro. For in vivo experiment, fetuses were administered STZ at 40 g/g on day 19 of gestation. The B-cell volume in pancreatic islets decreased markedly 3 hr after the administration of STZ, but it began to increase after 6 hr. The fetal plasma insulin concentration decreased from 6 to 12 hr after the administration, but recovered after 48 hr. The cell division index in fetal pancreatic islets of the STZ-treated group began to be significantly larger after 6 hr. For in vitro experiment, fetal pancreases on day 18 of gestation were pretreated with 10 mM STZ for 6 hr and cultured for 98 hr. B-cells were completely destroyed with STZ treatment; however, as these pancreases were cultured in a medium free of STZ, B-cells began to appear and insulin secretion was detected after 48 hr. After 72 hr, the cell division index was significantly greater. These results suggest that the fetal pancreas treated with STZ has the ability to regenerate B-cells both in vivo and in vitro.

show abstract

“…During embryogenesis, stem cells within the pancreatic duct epithelium give rise to both the endocrine and acinar cells of the pancreas [51]. Adult pancreatic duct cells retain the capacity for expansion and differentiation suggesting that adult pancreatic ducts may still harbor stem cells capable of differentiating into ß-cells in vivo [52][53][54]. This notion is supported by the ability of ductal tissue in vitro to be harvested, expanded, and cultured to form islet-like structures capable of glucose responsive insulin secretion [54].…”

Section: Pancreatic Stem Cellsmentioning

confidence: 99%

Cellular Therapies for Type 1 Diabetes

Lee¹,

Grossman²,

Chong³

2008

Horm Metab Res

View full text Add to dashboard Cite

Type 1 diabetes mellitus (T1DM) is a disease that results from the selective autoimmune destruction of insulin-producing β-cells. This disease process lends itself to cellular therapy because of the single cell nature of insulin production. Murine models have provided opportunities for the study of cellular therapies for the treatment of diabetes, including the investigation of islet transplantation, and also the possibility of stem cell therapies and islet regeneration. Studies in islet transplantation have included both allo-and xeno-transplantation and have allowed for the study of new approaches for the reversal of autoimmunity and achieving immune tolerance. Stem cells from hematopoietic sources such as bone marrow and fetal cord blood, as well as from the pancreas, intestine, liver and spleen promises either new sources of islets or may function as stimulators of islet regeneration. This review will summarize the various cellular interventions investigated as potential treatments of T1DM.

show abstract

Induction of Islet Cytodifferentiation by Fetal Mesenchyme in Adult Pancreatic Ductal Epithelium

Cited by 80 publications

References 15 publications

Formation of insulin-positive cells in implants of human pancreatic duct cell preparations from young donors

Formation of insulin-positive cells in implants of human pancreatic duct cell preparations from young donors

Recovery in the fetal pancreatic islet following fetal administration of streptozotocin in the rat in vivo and in vitro

Cellular Therapies for Type 1 Diabetes

Contact Info

Product

Resources

About