Lecture 10 - Cell & Tissue Engineering

Regulation of cell behavior

What biochemical factors contribute to the cell environment

• Cell-cell junctions

• Cytokines

• Growth factors

• ECM proteins and matricellular proteins

Why is the extracellular environment important?

• Critical for the control of cell behavior in any tissues (The extracellular milieu)

• Bioactive environment that varies between various tissues and conditions.

How do biochemical factors contribute to cell environment?

• Participate in the regulation of cell surface protein activity leading to intracellular signal transduction and gene expression that control cell proliferation, migration, differentiation and tissue formation.

What is a bioactive environment in tissue engineering?

• Can be created by incorporating different factors in the scaffold, such as:

  • Cell adhesion factors

  • Matricellular proteins

  • Growth factors

  • Hormones

  • Cytokines

• Can be in soluble form or attached to the scaffold!

Matricellular Proteins

• Secreted proteins that are associated to ECM but not part of the ECM structure.

  • Link between the ECM & cell surface receptors

  • Regulatory functions

Examples of Matricellular Proteins

• Thrombospondin 1 and 2 (TSP)

• Tenascin-C

• Osteopontin

• SPARC

SPARC

• Secreted Protein Acidic and Rich in Cystein

• Found in tissues with active remodeling

  • Gut epithelium w/ rapid turnover

  • Wound Healing

• Binds to growth factors (PDGF-AB and BB)

  • Binds to VEGF as well * inhibit VEGF-induced endothelial cell growth

• Influence change in cell shapes

Growth Factors (GFs)

• Protein secreted in the extracellular environment

• Regulate cell division and cell survival

• Can be produced in vitro

• Bind to cell membrane receptors

  • Induce signal transduction and cascade of signalization

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Examples of GFs

• EGF

• FGF

• PDGF

• BMP

Hormones

• Chemical messengers that carry specific signals in the blood stream from a cell or gland to other tissues.

• Maintain homeostasis.

• Action of hormone, regulated by numerous factors including, concentration, pattern of secretion, type of receiving cell.

• Bound to plasma proteins.

Antagonistic Hormones

• Insulin

  • Lower glucose level

• Glucagon

  • Increase glucose level

Cytokines

• Small secreted proteins released by cells that have a specific effect on cell-cell interactions & communication.

• General term that include:

  • Lymphokines (prod. by lymphocytes)

  • Monokines (prod. by monocytes & macrophages)

  • Chemokines

  • Interleukins (prod. by leukocytes)

• Most often prod. (Cytokines) by helper T Cells and macrophages!