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Related Concept Videos

Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore called induced pluripotent stem...

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Aggregate Size Optimization in Microwells for Suspension-based Cardiac Differentiation of Human Pluripotent Stem Cells
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A microparticle approach to morphogen delivery within pluripotent stem cell aggregates.

Andrés M Bratt-Leal1, Anh H Nguyen, Katy A Hammersmith

  • 1The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0535, USA.

Biomaterials
|July 6, 2013
PubMed
Summary

Microparticles deliver growth factors to direct stem cell differentiation more efficiently than soluble methods. This localized delivery in 3D cultures enables precise control over cell fate and aids in studying morphogen gradients for stem cell technologies.

Keywords:
Bone morphogenic proteinDifferentiationEmbryoid bodyEmbryonic stem cellsMesodermMicroparticle

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Area of Science:

  • Biomaterials science
  • Stem cell biology
  • Tissue engineering

Background:

  • Stem cell fate is influenced by the 3D microenvironment and extrinsic cues.
  • Biomaterials offer a method to control the presentation of morphogens for stem cell differentiation.
  • Current methods for growth factor delivery can be inefficient and require large quantities.

Purpose of the Study:

  • To develop and evaluate a microparticle (MP)-based approach for delivering growth factors within multicellular aggregates.
  • To direct pluripotent stem cell differentiation using localized growth factor presentation.
  • To compare the efficiency of MP-based delivery with conventional soluble delivery methods.

Main Methods:

  • Developed gelatin microparticles (MPs) loaded with specific growth factors (BMP4 or noggin).
  • Delivered MPs within multicellular stem cell aggregates to direct differentiation.
  • Utilized whole-mount confocal imaging and flow cytometry to assess gene expression and cell differentiation.
  • Investigated spatial control by localizing MPs within specific regions of the aggregates.

Main Results:

  • Gelatin MPs laden with BMP4 or noggin induced efficient mesoderm and ectoderm lineage gene expression, respectively.
  • MP delivery used significantly less total growth factor (nearly 12-fold reduction) compared to soluble methods.
  • BMP4-laden MPs increased the percentage of cells expressing a specific lineage marker (Brachyury-T promoter-GFP).
  • Localized MP delivery allowed for spatial control of stem cell differentiation within 3D cultures.

Conclusions:

  • Microparticle-based delivery of growth factors within stem cell aggregates is a highly efficient method for directing differentiation.
  • This approach offers precise spatial and temporal control over morphogen presentation in 3D cultures.
  • Localized MP delivery represents a scalable technology for stem cell differentiation and the study of morphogen gradients.