Spatiotemporal proliferation of human stromal cells adjusts to nutrient availability and leads to stanniocalcin-1 expression in vitro and in vivo

G.A. Higuera, H. Fernandes, T.W.G.M. Spitters, A.J.B. van Boxtel

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results showed that nutrient gradients prompt the spatiotemporal organization of MSCs in 3D culture. Cells adapted to their 3D environment without significant cell death or cell differentiation. Kinetics data and whole-genome gene expression analysis suggest that a low proliferation activity phenotype predominates in stromal cells cultured in 3D, likely due to increasing nutrient limitation. These differences implied that despite similar surface areas available for cell attachment, higher cell concentrations in 3D reduced MSCs proliferation, while activating hypoxia related-pathways. To further understand the in vivo effects of both proliferation and cell concentrations, we increased cell concentrations in small (1.8 ml) implantable wells. We found that MSCs accumulation and conditioning by nutrient competition in small volumes leads to an ideal threshold of cell-concentration for the induction of blood vessel formation, possibly signaled by the hypoxia-related stanniocalcin-1 gene.
Original languageEnglish
Pages (from-to)190-202
JournalBiomaterials
Volume61
DOIs
Publication statusPublished - 2015

Fingerprint

Stromal Cells
Nutrients
Availability
Food
Genes
Blood vessels
Cell proliferation
Cell death
Gene expression
Bone
Cells
Tissue
Kinetics
Cell Proliferation
teleocalcin
In Vitro Techniques
Cell Lineage
Blood Vessels
Cell Differentiation
Cell Death

Keywords

  • mesenchymal stem-cells
  • tissue engineering scaffolds
  • bone-marrow
  • mechanical compression
  • mathematical-model
  • progenitor cells
  • up-regulation
  • shear-stress
  • gradients
  • oxygen

Cite this

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title = "Spatiotemporal proliferation of human stromal cells adjusts to nutrient availability and leads to stanniocalcin-1 expression in vitro and in vivo",
abstract = "Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results showed that nutrient gradients prompt the spatiotemporal organization of MSCs in 3D culture. Cells adapted to their 3D environment without significant cell death or cell differentiation. Kinetics data and whole-genome gene expression analysis suggest that a low proliferation activity phenotype predominates in stromal cells cultured in 3D, likely due to increasing nutrient limitation. These differences implied that despite similar surface areas available for cell attachment, higher cell concentrations in 3D reduced MSCs proliferation, while activating hypoxia related-pathways. To further understand the in vivo effects of both proliferation and cell concentrations, we increased cell concentrations in small (1.8 ml) implantable wells. We found that MSCs accumulation and conditioning by nutrient competition in small volumes leads to an ideal threshold of cell-concentration for the induction of blood vessel formation, possibly signaled by the hypoxia-related stanniocalcin-1 gene.",
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author = "G.A. Higuera and H. Fernandes and T.W.G.M. Spitters and {van Boxtel}, A.J.B.",
year = "2015",
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Spatiotemporal proliferation of human stromal cells adjusts to nutrient availability and leads to stanniocalcin-1 expression in vitro and in vivo. / Higuera, G.A.; Fernandes, H.; Spitters, T.W.G.M.; van Boxtel, A.J.B.

In: Biomaterials, Vol. 61, 2015, p. 190-202.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Spatiotemporal proliferation of human stromal cells adjusts to nutrient availability and leads to stanniocalcin-1 expression in vitro and in vivo

AU - Higuera, G.A.

AU - Fernandes, H.

AU - Spitters, T.W.G.M.

AU - van Boxtel, A.J.B.

PY - 2015

Y1 - 2015

N2 - Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results showed that nutrient gradients prompt the spatiotemporal organization of MSCs in 3D culture. Cells adapted to their 3D environment without significant cell death or cell differentiation. Kinetics data and whole-genome gene expression analysis suggest that a low proliferation activity phenotype predominates in stromal cells cultured in 3D, likely due to increasing nutrient limitation. These differences implied that despite similar surface areas available for cell attachment, higher cell concentrations in 3D reduced MSCs proliferation, while activating hypoxia related-pathways. To further understand the in vivo effects of both proliferation and cell concentrations, we increased cell concentrations in small (1.8 ml) implantable wells. We found that MSCs accumulation and conditioning by nutrient competition in small volumes leads to an ideal threshold of cell-concentration for the induction of blood vessel formation, possibly signaled by the hypoxia-related stanniocalcin-1 gene.

AB - Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results showed that nutrient gradients prompt the spatiotemporal organization of MSCs in 3D culture. Cells adapted to their 3D environment without significant cell death or cell differentiation. Kinetics data and whole-genome gene expression analysis suggest that a low proliferation activity phenotype predominates in stromal cells cultured in 3D, likely due to increasing nutrient limitation. These differences implied that despite similar surface areas available for cell attachment, higher cell concentrations in 3D reduced MSCs proliferation, while activating hypoxia related-pathways. To further understand the in vivo effects of both proliferation and cell concentrations, we increased cell concentrations in small (1.8 ml) implantable wells. We found that MSCs accumulation and conditioning by nutrient competition in small volumes leads to an ideal threshold of cell-concentration for the induction of blood vessel formation, possibly signaled by the hypoxia-related stanniocalcin-1 gene.

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KW - tissue engineering scaffolds

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KW - mathematical-model

KW - progenitor cells

KW - up-regulation

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