Aim: Adipose-derived stem cells (ADSCs) therapies are emerging as a promising approach to therapeutic angiogenesis. Therapeutic persistence and reduced primitive stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches.
Methods: Cultured ADSCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Photoactivated and non-light-treated ADSCs were injected into the tail vein of mice fed a high-fat diet (HFD), following which unilateral hindlimb ischemia was induced. Laser Doppler imaging was conducted to measure the blood flow reperfusion. Capillary density was measured in the ischemic gastrocnemius muscle. mRNA levels of angiogenic factors were determined by reverse-transcription polymerase chain reaction, Flow cytometry was used to determine the characterization of ADSCs and endothelial progenitor cell (EPC). Human ADSCs secretomes were analyzed by liquid chromatography tandem mass spectrometry.
Results: Our study demonstrated that photoactivated ND-ADSCs prolonged functional blood flow perfusion and increased ADSCs-derived EPC and neovascularization thirty-eight days after ligation, when compared with saline-treated controls. Profiling analysis in ischemic muscles showed upregulation of genes associated with pro-angiogenic factors after injection of photoactivated ND-ADSCs when compared with the non-light-treated ADSCs or saline treated HFD mice. Mass spectrometry revealed that light-treated ADSCs conditioned medium retained a more complete pro-angiogenic activity with significant upregulation of angiogenesis related proteins.
Conclusion: Our data demonstrates that photoactivated ND-ADSCs improve blood flow recovery and their injection may prove to be a useful strategy for the prevention and treatment of diabetic peripheral arterial disease.
X. Fan: None. J. Wu: Research Support; Self; HarmonyRegena Inc.