Prolonged therapeutic effects of photoactivated adipose‐derived stem cells following ischaemic injury

Abstract

AimAdipose‐derived stem cells (ASCs) 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.MethodsCultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Unilateral hindlimb ischaemia model was induced in high‐fat diet (HFD)‐fed mice by femoral artery interruption, after which photoactivated and non‐light‐treated ASCs were injected into the tail vein of mice. Laser Doppler imaging was conducted to measure the blood flow reperfusion. Capillary density was measured in the ischaemic gastrocnemius muscle. mRNA levels of angiogenic factors were determined by reverse‐transcription polymerase chain reaction. Flow cytometry was used to determine the characterization of ASCs and endothelial progenitor cell (EPC). Human ASCs secretomes were analysed by liquid chromatography tandem mass spectrometry.ResultsOur study demonstrated that photoactivated ND‐ASCs prolonged functional blood flow perfusion and increased ASCs‐derived EPC and neovascularization 38 days after ligation, when compared with saline‐treated controls. Profiling analysis in ischaemic muscles showed upregulation of genes associated with pro‐angiogenic factors after injection of photoactivated ND‐ASCs when compared with the non‐light‐treated ASCs or saline treated HFD mice. Mass spectrometry revealed that light‐treated ASCs conditioned medium retained a more complete pro‐angiogenic activity with significant upregulation of angiogenesis related proteins.ConclusionOur data demonstrates that photoactivated ND‐ASCs improve blood flow recovery and their injection may prove to be a useful strategy for the prevention and treatment of diabetic peripheral arterial disease.

Coronary Endothelium No‐Reflow Injury Is Associated with ROS‐Modified Mitochondrial Fission through the JNK‐Drp1 Signaling Pathway

“…A sulfuric acid solution was added to stop the reaction, and the color was analyzed using spectrophotometry at a wavelength of 450 nm [28]. The concentrations of SOD, GPX, GSH, and MDA in the culture media were then calculated according to the standard curve [29].…”

In situ transplantation of adipose-derived stem cells via photoactivation improves glucose metabolism in obese mice

“…Accumulating studies have demonstrated the benefits of photoactivation as a promising and rapidly expanding physical approach in various pathologies, especially for reducing inflammatory responses and promoting tissue regeneration [12,14,16]. Using our specifically developed device with more refined wavelengths of light, we demonstrated that photoactivation shifted M1-to-M2 ATMs, and transplantation of the treated fat into the visceral adipose tissue improves glucose tolerance in obese mice [14].…”

“…Eight-week-old male C57BL/6J mice were fed a high-fat diet (HFD) (TP2330055A; Research Diet, Trophic Animal Feed High-tech Co. Ltd, China) for 16 weeks as described previously [12]. Age-matched male mice that were fed a normal diet were used as controls.…”

“…Several studies have shown that the intravenous infusion of MSCs has the potential to improve glucose homeostasis in diabetic animals by activating the insulin-signaling pathway and increasing the expression and membrane transposition of glucose transporters [8][9][10]. MSCs have been shown to modulate the microenvironment of pathological tissues contributing to repair and regeneration through secreting anti-inflammatory molecules [11][12][13]. We and others have demonstrated that fat tissue transplantation could reduce fat depot-selective ATM infiltration in obese mice [14,15].…”

“…Using our specifically developed device with more refined wavelengths of light, we demonstrated that photoactivation shifted M1-to-M2 ATMs, and transplantation of the treated fat into the visceral adipose tissue improves glucose tolerance in obese mice [14]. Most recently, intravenous infusion of adipose-derived stem cells (ASCs) has shown that photoactivation prolonged functional blood flow perfusion and increased ASCs-derived EPC and neovascularization [12].…”