Backgroud:
Although treatment by endogenous stem cell recruitment is one of the promising therapeutic options for the damaged tissues, the therapeutic efficacy is not enough to repair the severely damaged heart. How to enhance migration of stem cells to injured site and confine them there may be key point to improve the therapeutic effects. In this study, we hypothesized that combined strategy of prostacyclin agonist (ONO1301), which is enhancer in stem cell recruitment, and laminin (LM) 511 as stem cell bed may enhance regeneration processes in failed heart.
Methods and Results:
To examine the therapeutic effect of ONO1301 and LM511, we administrated ONO1301 and LM511 immersed collagen sheet (Combination group), only LM511 immersed collagen sheet (LM group), only ONO1301 immersed collagen sheet (ONO group), and PBS immersed collagen sheet (control) to rat acute infarction model. Four weeks later, qPCR analysis and histological analysis revealed that the expression of cytokines related to cell migration or angiogenesis were significantly higher in the combination group as compared to the other groups. The number of mesenchymal stem cell (PDGFRα and CD90 double positive cells) tended to be higher in the combination group compared to the other groups (combination: 388 ± 7 cells/mm
2
, LM: 292 ± 34 cells/mm
2
, ONO: 216 ± 30 cells/mm
2
, control: 160 ± 34 cells/mm
2
). In addition, the number of matured arterioles which have both endothelial cells and smooth muscle cells was markedly higher in the combination group compared to the control group (combination: 616 ± 44 cells/mm
2
, control: 226 ± 60cells/mm
2
; p < 0.05). In addition, infarct size was remarkably reduced in the combination group than the other groups (combination: 11.5 ± 0.1%, LM: 14.8 ± 0.8%, ONO: 23.6 ± 2.9%, control: 29.2 ± 2.0%). Ultrasonographically, ejection fraction significantly improved in the combination group compared to the other groups (combination: 55.0 ± 0.9%, LM: 51.6 ± 1.4%, ONO: 46.9 ± 1.4%, control: 43.5 ± 2.9%).
Conclusion:
The combined administration of LM511 and ONO1301 promotes arteriogenesis by enhanced endogenous repair with declined infarct size and improved cardiac function in rat acute myocardial infarction model, proposing new therapeutic strategy for ischemic cardiomyopathy.
Endogenous Stem Cell‐Based In Situ Tissue Regeneration Using Electrostatically Interactive Hydrogel with a Newly Discovered Substance P Analog and VEGF‐Mimicking Peptide (Small 40/2021)
