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Related Experiment Video

Updated: May 3, 2026

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function
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Novel Directly Reprogrammed Smooth Muscle Cells Promote Vascular Regeneration as Microvascular Mural Cells.

Cholomi Jung1,2, Ji Woong Han3, Shin-Jeong Lee2

  • 1Department of Internal Medicine (C.J., E.J.L.), Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea.

Circulation
|February 13, 2025
PubMed
Summary

Directly reprogramming human fibroblasts into contractile smooth muscle cells (SMCs) using specific factors created a novel cell therapy. These reprogrammed SMCs (rSMCs) effectively repaired vascular damage and promoted blood vessel formation in ischemic limbs.

Keywords:
cellular reprogramming techniquesfibroblastsischemiamyocytes, smooth muscleneovascularization, physiologicpericytesregeneration

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Area of Science:

  • Regenerative Medicine
  • Vascular Biology
  • Cell Therapy

Background:

  • Cell therapy shows promise for neovascularization but often limited to capillaries.
  • Larger, stable vessels require mural cells like smooth muscle cells (SMCs) or pericytes.
  • Existing direct reprogramming methods yield SMCs lacking genuine contractile function.

Purpose of the Study:

  • To directly reprogram human dermal fibroblasts into contractile SMCs (rSMCs).
  • To investigate the role of rSMCs in forming vascular mural cells in vivo.
  • To evaluate the therapeutic effects of rSMCs on ischemic disease.

Main Methods:

  • Human dermal fibroblasts were reprogrammed using myocardin and all-trans retinoic acid.
  • Phenotype and contractility of reprogrammed SMCs (rSMCs) were characterized.
  • rSMCs were transplanted into a mouse hindlimb ischemia model to assess therapeutic effects and vessel formation.

Main Results:

  • Novel culture conditions efficiently reprogrammed fibroblasts into contractile rSMCs.
  • Transplanted rSMCs enhanced blood flow recovery and vascular repair in ischemic limbs.
  • rSMCs integrated into vascular walls, forming larger, stable microvessels and exerting regenerative effects.

Conclusions:

  • Myocardin and all-trans retinoic acid reprogramming yields functional SMCs from fibroblasts.
  • rSMCs promote vascular repair and neovascularization via mural cell incorporation and paracrine signaling.
  • These human rSMCs offer a novel source for cell-based therapy and research.