Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration

Biomaterials. 2015 Dec;73:51-9. doi: 10.1016/j.biomaterials.2015.09.008. Epub 2015 Sep 11.

Abstract

Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue.

Keywords: Cardiovascular progenitor cell; Human induced pluripotent stem cell; Macroporous nanofibrous scaffold; Tissue-engineered vascular tissue; Vascular smooth muscle cell.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Aorta / pathology
  • Blood Vessel Prosthesis*
  • Cell Differentiation
  • Cell Lineage
  • Female
  • Flow Cytometry
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Leukocytes, Mononuclear / cytology
  • Mesoderm
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Microscopy, Electron, Scanning
  • Microscopy, Fluorescence
  • Muscle, Smooth, Vascular / cytology
  • Myocardial Contraction
  • Myocytes, Smooth Muscle / cytology
  • Pluripotent Stem Cells / cytology
  • Polyesters / chemistry
  • Porosity
  • Regeneration*
  • Tissue Engineering / methods*

Substances

  • Antigens, CD34
  • Polyesters
  • poly(lactide)