Abstract
Despite progress in our knowledge about pancreatic islet specification, most attempts at differentiating stem/progenitor cells into functional, transplantable β cells have met only with moderate success thus far. A major challenge is the intrinsic simplicity of in vitro culture systems, which cannot approximate the physiological complexity of in vivo microenvironments. Oxygenation is a critical limitation of standard culture methods, and one of special relevance for the development of β cells, known for their high O2 requirements. Based on our understanding of islet physiology, we have tested the hypothesis that enhanced O2 delivery (as provided by novel perfluorocarbon-based culture devices) may result in higher levels of β-cell differentiation from progenitor cells in vitro. Using a mouse model of pancreatic development, we demonstrate that a physiological-like mode of O2 delivery results in a very significant upregulation of endocrine differentiation markers (up to 30-fold for insulin one and 2), comparable to relevant in vivo controls. This effect was not observed by merely increasing environmental O2 concentrations in conventional settings. Our findings indicate that O2 plays an important role in the differentiation of β cells from their progenitors and may open the door to more efficient islet differentiation protocols from embryonic and/or adult stem cells.
| Original language | English |
|---|---|
| Pages (from-to) | 3155-3164 |
| Number of pages | 10 |
| Journal | Stem Cells |
| Volume | 25 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2007 |
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Keywords
- β cells
- Islets
- Oxygenation
- Perfluorocarbon
- Stem cells
ASJC Scopus subject areas
- Cell Biology
Cite this
Enhanced oxygenation promotes β-cell differentiation in vitro. / Fraker, Christopher; Álvarez, Silvia; Papadopoulos, Panagiotis; Giraldo, Jaime; Gu, Weiyong; Ricordi, Camillo; Inverardi, Luca A; Dominguez-Bendala, Juan.
In: Stem Cells, Vol. 25, No. 12, 01.12.2007, p. 3155-3164.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhanced oxygenation promotes β-cell differentiation in vitro
AU - Fraker, Christopher
AU - Álvarez, Silvia
AU - Papadopoulos, Panagiotis
AU - Giraldo, Jaime
AU - Gu, Weiyong
AU - Ricordi, Camillo
AU - Inverardi, Luca A
AU - Dominguez-Bendala, Juan
PY - 2007/12/1
Y1 - 2007/12/1
N2 - Despite progress in our knowledge about pancreatic islet specification, most attempts at differentiating stem/progenitor cells into functional, transplantable β cells have met only with moderate success thus far. A major challenge is the intrinsic simplicity of in vitro culture systems, which cannot approximate the physiological complexity of in vivo microenvironments. Oxygenation is a critical limitation of standard culture methods, and one of special relevance for the development of β cells, known for their high O2 requirements. Based on our understanding of islet physiology, we have tested the hypothesis that enhanced O2 delivery (as provided by novel perfluorocarbon-based culture devices) may result in higher levels of β-cell differentiation from progenitor cells in vitro. Using a mouse model of pancreatic development, we demonstrate that a physiological-like mode of O2 delivery results in a very significant upregulation of endocrine differentiation markers (up to 30-fold for insulin one and 2), comparable to relevant in vivo controls. This effect was not observed by merely increasing environmental O2 concentrations in conventional settings. Our findings indicate that O2 plays an important role in the differentiation of β cells from their progenitors and may open the door to more efficient islet differentiation protocols from embryonic and/or adult stem cells.
AB - Despite progress in our knowledge about pancreatic islet specification, most attempts at differentiating stem/progenitor cells into functional, transplantable β cells have met only with moderate success thus far. A major challenge is the intrinsic simplicity of in vitro culture systems, which cannot approximate the physiological complexity of in vivo microenvironments. Oxygenation is a critical limitation of standard culture methods, and one of special relevance for the development of β cells, known for their high O2 requirements. Based on our understanding of islet physiology, we have tested the hypothesis that enhanced O2 delivery (as provided by novel perfluorocarbon-based culture devices) may result in higher levels of β-cell differentiation from progenitor cells in vitro. Using a mouse model of pancreatic development, we demonstrate that a physiological-like mode of O2 delivery results in a very significant upregulation of endocrine differentiation markers (up to 30-fold for insulin one and 2), comparable to relevant in vivo controls. This effect was not observed by merely increasing environmental O2 concentrations in conventional settings. Our findings indicate that O2 plays an important role in the differentiation of β cells from their progenitors and may open the door to more efficient islet differentiation protocols from embryonic and/or adult stem cells.
KW - β cells
KW - Islets
KW - Oxygenation
KW - Perfluorocarbon
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=37349054204&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37349054204&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2007-0445
DO - 10.1634/stemcells.2007-0445
M3 - Article
C2 - 17761759
AN - SCOPUS:37349054204
VL - 25
SP - 3155
EP - 3164
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 12
ER -