Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages

  title={Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages},
  author={Raewyn M. Seaberg and Simon R. Smukler and Timothy J. Kieffer and Grigori Enikolopov and Zeenat Asghar and Michael B. Wheeler and Gregory S. Korbutt and Derek van der Kooy},
  journal={Nature Biotechnology},
The clonal isolation of putative adult pancreatic precursors has been an elusive goal of researchers seeking to develop cell replacement strategies for diabetes. We report the clonal identification of multipotent precursor cells from the adult mouse pancreas. The application of a serum-free, colony-forming assay to pancreatic cells enabled the identification of precursors from pancreatic islet and ductal populations. These cells proliferate in vitro to form clonal colonies that coexpress neural… 

The adult mouse and human pancreas contain rare multipotent stem cells that express insulin.

Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACS

Previously undescribed strategies for prospective purification and analysis of pancreatic endocrine progenitor cells that should accelerate studies of islet development and replacement are revealed.

Isolation and characterization of mesenchymal stem cells from cultured human pancreatic islets of langerhans

It is shown for the first time that nestin positive MSC isolated from human adult pancreas, bone marrow and adipose tissue represent stem / progenitor cells with the potential to induce pancreatic developmental genes.

The adult mammalian pancreas contains separate precursors of pancreatic and neural crest developmental origins.

Evidence suggests that there are at least two distinct types of precursors present in adult pancreatic islets, one of pancreatic origin and one of neural crest origin, which are distinct in their gene expression and differentiation potential.

In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas.

Three 3-dimensional colony assays for pancreatic progenitors are devised to address the questions of self-renewal and multi-lineage differentiation-two criteria necessary to define a stem cell.

Differentiation of Insulin-Producing Cells from Human Neural Progenitor Cells

It is shown that brain-derived human neural progenitor cells, exposed to a series of signals that regulate in vivo pancreatic islet development, form clusters of glucose-responsive insulin-producing cells (IPCs), and production of IPCs solely through extracellular factor modulation in the absence of genetic manipulations may promote strategies to derive transplantable islet-replacement tissues.

Multipotent progenitor cells isolated from adult human pancreatic tissue.

Is Stage-Specific Embryonic Antigen 4 a Marker for Human Ductal Stem/Progenitor Cells?

It is hypothesize that S SEA4+ cells or a subpopulation of those cells residing in the pancreatic ducts may be the elusive PnSCs, and in this case, SSEA4 may represent a potential surface antigen marker for human Pn SCs.

Rapid and efficient in vitro generation of pancreatic islet progenitor cells from nonendocrine epithelial cells in the adult human pancreas.

A significant advancement in the differentiation of an adult pancreatic progenitor cell population in vitro is suggested and suggests that the nonendocrine compartment of the human pancreas remains an important cell resource for the generation of transplantable islets to treat diabetes.

The Implications of Developmental and Evolutionary Relationships between Pancreatic Beta-cells and Neurons

Evidence presented here shows that pancreatic stem cells express insulin and produce multiple endocrine, exocrine and neural cells in vitro and in vivo, which could provide the tissue necessary for widespread β-cell transplantation therapy for diabetes.



Stem/progenitor cells derived from adult tissues: potential for the treatment of diabetes mellitus.

  • A. LechnerJ. Habener
  • Biology, Medicine
    American journal of physiology. Endocrinology and metabolism
  • 2003
In future studies, more stringent criteria should be met to clonally define adult islet/beta-cell progenitor cells, and the utilization of these cells for the generation of insulin-producing beta-cells in vitro seems to be feasible in the near future.

Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes.

It is proposed that nestin-positive islet-derived progenitor (NIP) cells are a distinct population of cells that reside within pancreatic islets and may participate in the neogenesis of islet endocrine cells.

Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets

This work generated cells expressing insulin and other pancreatic endocrine hormones from mouse ES cells that self-assemble to form three-dimensional clusters similar in topology to normal pancreatic islets where pancreatic cell types are in close association with neurons.

Characterization and isolation of promoter-defined nestin-positive cells from the human fetal pancreas.

It is concluded that nestin is not a specific marker of beta-cell precursors in the developing human pancreas, and nestin- fetal pancreatic epithelial cells gave rise to functional insulin-secreting beta-cells.

Heterogenous expression of nestin in human pancreatic tissue precludes its use as an islet precursor marker.

A diffuse and variable expression of nestin in human pancreas is shown that may be due to a number of different processes, including post-mortem tissue remodeling and cellular differentiation.

Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation

This work introduces a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest and suggests that terminally differentiated β-cells retain a significant proliferative capacity in vivo and casts doubt on the idea that adult stem cells have a significant role in β-cell replenishment.

Nestin-expressing cells in the pancreatic islets of Langerhans.

Evidence is presented that a subset of cells in the pancreatic islets express the stem cell marker nestin, which might serve as precursors of differentiated pancreatic endocrine cells.

Nestin-lineage cells contribute to the microvasculature but not endocrine cells of the islet.

The results indicate that both in vivo and in vitro pancreatic endocrine cells arise independently of nestin-positive precursors, suggesting that nestIn-positive cells play an important role in the growth and maintenance of the islet.