Engineered M13 Peptide Carrier Promotes Angiogenic Potential of Patient-Derived Human Cardiac Progenitor Cells and In Vivo Engraftment

Tissue Eng Regen Med. 2020 Jun;17(3):323-333. doi: 10.1007/s13770-020-00244-w. Epub 2020 Mar 29.

Abstract

Background: Despite promising advances in stem cell-based therapy, the treatment of ischemic cardiovascular diseases remains a big challenge due to both the insufficient in vivo viability of transplanted cells and poor angiogenic potential of stem cells. The goal of this study was to develop therapeutic human cardiac progenitor cells (hCPCs) for ischemic cardiovascular diseases with a novel M13 peptide carrier.

Method: In this study, an engineered M13 peptide carrier was successfully generated using a QuikChange Kit. The cellular function of M13 peptide carrier-treated hCPCs was assessed using a tube formation assay and scratch wound healing assay. The in vivo engraftment and cell survival bioactivities of transplanted cells were demonstrated by immunohistochemistry after hCPC transplantation into a myocardial infarction animal model.

Results: The engineered M13RGD+SDKP peptide carrier, which expressed RGD peptide on PIII site and SDKP peptide on PVIII site, did not affect morphologic change and proliferation ability in hCPCs. In contrast, hCPCs treated with M13RGD+SDKP showed enhanced angiogenic capacity, including tube formation and migration capacity. Moreover, transplanted hCPCs with M13RGD+SDKP were engrafted into the ischemic region and promoted in vivo cell survival.

Conclusion: Our present data provides a promising protocol for CPC-based cell therapy via short-term cell priming of hCPCs with engineered M13RGD+SDKP before cell transplantation for treatment of cardiovascular disease.

Keywords: Cardiac progenitor cell; Cardiovascular diseases; M13 bacteriophage; RGD; SDKP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Bacteriophage M13 / genetics
  • Cardiovascular Diseases
  • Cell Survival
  • Endothelial Cells
  • Genetic Engineering
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Myocardial Infarction / therapy*
  • Myocytes, Cardiac / transplantation
  • Peptides / metabolism*
  • Peptides / pharmacology
  • Stem Cell Transplantation*
  • Stem Cells / drug effects*
  • Wound Healing

Substances

  • Angiogenesis Inducing Agents
  • Peptides