Background <p>Using several strategies, the stimulation of angiogenesis can alleviate the pathological complications of post-myocardial ischemia. Here, endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) were pre-cultured inside the alginate/gelatin (Alg/Gel) microspheres in the presence of SDF-1α for 7 days, and their angiogenesis potential was monitored in infarcted rabbits.</p> Methods <p>The decapsulated cells were monitored in terms of cell dynamic growth and angiogenesis potential in vitro and after injection into ischemic myocardium in rabbits.</p> Results <p>Based on the data, 7-day incubation inside the Alg/Gel microspheres led to the stimulation of angiogenesis profile (Ang-1↑, -2↑, Tie-2↑), migration (MMP-2↑, and − 9↑), and autophagic response (Beclin-1↑, LC3↑, and p-62↓) in EPCs containing groups in the presence of SDF-1α. PCR array analysis revealed the expression of angiogenesis-related genes in the presence of SDF-1α. These features coincided with the stimulation of in vitro tubulogenesis properties in EPCs and EPCs + SDF-1α groups. The injection of cells from different groups into the infarcted rabbits led to the reduction of fibrotic area in ischemic myocardium in MSCs-bearing groups, and these effects were intensified in the presence of SDF-1α. Pre-treatment of EPCs and MSCs increased the recruited immune cells into the ischemic area within the myocardium. It was suggested that SDF-1α stimulated the local vascular density (CD31 capillaries, and α-SMA arterioles) in EPCs-bearing groups compared to MSCs and MSCs + SDF-1α groups.</p> Conclusions <p>These data indicate that pre-culture of EPCs and MSCs inside the Alg-based hydrogels can increase the regenerative potential of these cells, especially when exposed to stimulatory cytokines such as SDF-1α for the alleviation of ischemic changes.</p>

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Intramyocardial injection of pre-cultured endothelial progenitor cells and mesenchymal stem cells inside alginate/gelatin microspheres induced angiogenesis in infarcted rabbits

  • Hassan Amini,
  • Çığır Biray Avci,
  • Sajed Nazif Kerdar,
  • Ayla Hassani,
  • Meisam Amini,
  • Narges Mardi,
  • Sepideh Saghati,
  • Maryam Taghavi Narmi,
  • Leila Sabour Takanlou,
  • Maryam Sabour Takanlou,
  • Ali Baradar Khoshfetrat,
  • Mohammad Nori,
  • Shahriar Hashemzadeh,
  • Reza Rahbarghazi

摘要

Background

Using several strategies, the stimulation of angiogenesis can alleviate the pathological complications of post-myocardial ischemia. Here, endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) were pre-cultured inside the alginate/gelatin (Alg/Gel) microspheres in the presence of SDF-1α for 7 days, and their angiogenesis potential was monitored in infarcted rabbits.

Methods

The decapsulated cells were monitored in terms of cell dynamic growth and angiogenesis potential in vitro and after injection into ischemic myocardium in rabbits.

Results

Based on the data, 7-day incubation inside the Alg/Gel microspheres led to the stimulation of angiogenesis profile (Ang-1↑, -2↑, Tie-2↑), migration (MMP-2↑, and − 9↑), and autophagic response (Beclin-1↑, LC3↑, and p-62↓) in EPCs containing groups in the presence of SDF-1α. PCR array analysis revealed the expression of angiogenesis-related genes in the presence of SDF-1α. These features coincided with the stimulation of in vitro tubulogenesis properties in EPCs and EPCs + SDF-1α groups. The injection of cells from different groups into the infarcted rabbits led to the reduction of fibrotic area in ischemic myocardium in MSCs-bearing groups, and these effects were intensified in the presence of SDF-1α. Pre-treatment of EPCs and MSCs increased the recruited immune cells into the ischemic area within the myocardium. It was suggested that SDF-1α stimulated the local vascular density (CD31 capillaries, and α-SMA arterioles) in EPCs-bearing groups compared to MSCs and MSCs + SDF-1α groups.

Conclusions

These data indicate that pre-culture of EPCs and MSCs inside the Alg-based hydrogels can increase the regenerative potential of these cells, especially when exposed to stimulatory cytokines such as SDF-1α for the alleviation of ischemic changes.