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CD4 T-cells regulate angiogenesis and myogenesis.

Brian J Kwee1, Erica Budina2, Alexander J Najibi1

  • 1John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA; Wyss Institute Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.

Biomaterials
|June 20, 2018
PubMed
Summary
This summary is machine-generated.

Certain CD4+ T-cells, specifically Th2 and Th17, promote blood vessel and muscle regeneration in ischemic diseases. This discovery aids in developing new immunomodulatory biomaterials for treating these conditions.

Keywords:
AngiogenesisBiomaterialMyogenesisRegenerative medicineT-cells

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Area of Science:

  • Immunology
  • Regenerative Medicine
  • Biomaterials Science

Background:

  • Ischemic diseases, like peripheral artery disease, impact millions globally.
  • CD4+ T-cells are known to regulate angiogenesis and myogenesis, but their specific phenotypes' roles in regeneration remain unclear.

Purpose of the Study:

  • To investigate how different CD4+ T-cell phenotypes (Th1, Th2, Th17, Treg) influence vascular and skeletal muscle regeneration in ischemic conditions.
  • To assess the potential of T-cell secreted factors, delivered via biomaterials, for therapeutic applications in ischemia.

Main Methods:

  • In vitro assays were performed using conditioned medium from Th1, Th2, Th17, and Treg cells.
  • Secreted factors were encapsulated in an injectable alginate biomaterial and tested in a murine model of ischemia.
  • Effects on angiogenesis, endothelial sprouting, and skeletal muscle precursor cell proliferation/differentiation were analyzed.

Main Results:

  • Th2 and Th17 T-cell conditioned medium significantly enhanced angiogenesis in vitro and in vivo, partly by stimulating endothelial sprouting.
  • Th1 conditioned medium induced vascular regression in vitro and offered no benefit to angiogenesis in vivo.
  • Th1, Th2, and Th17 conditioned medium promoted muscle precursor cell proliferation but inhibited differentiation in vitro, prolonging early muscle regeneration stages in vivo. Treg conditioned medium showed minimal effects.

Conclusions:

  • Th2 and Th17 T-cells show promise in enhancing angiogenesis and myogenesis in ischemic injuries.
  • These findings support the development of immunomodulatory biomaterials leveraging specific T-cell phenotypes for treating ischemic diseases.