SDF-1α-Releasing Microspheres Effectively Extend Stem Cell Homing after Myocardial Infarction

Abstract

Ischemic heart disease (IHD) is one of the main focuses in today’s healthcare due to its implications and complications, and it is predicted to be increasing in prevalence due to the ageing population. Although the conventional pharmacological and interventional methods for the treatment of IHD presents with success in the clinical setting, the long-term complications of cardiac insufficiency are on a continual incline as a result of post-infarction remodeling of the cardiac tissue. The migration and involvement of stem cells to the cardiac muscle, followed by differentiation into cardiac myocytes, has been proven to be the natural process, though at a slow rate. SDF-1α is a novel candidate to mobilize stem cells homing to the ischemic heart. Endogenous SDF-1α levels are elevated after myocardial infarction, but their presence gradually decreases after approximately seven days. Additional administration of SDF-1α-releasing microspheres could be a tool for the extension of the time the stem cells are in the cardiac tissue after myocardial infarction. This, in turn, could constitute a novel therapy for more efficient regeneration of the heart muscle after injury. Through this practical study, it has been shown that the controlled release of SDF-1α from biodegradable microspheres into the pericardial sac fourteen days after myocardial infarction increases the concentration of exogenous SDF-1α, which persists in the tissue much longer than the level of endogenous SDF-1α. In addition, administration of SDF-1α-releasing microspheres increased the expression of the factors potentially involved in the involvement and retention of myocardial stem cells, which constitutes vascular endothelial growth factor A (VEGFA), stem cell factor (SCF), and vascular cell adhesion molecules (VCAMs) at the site of damaged tissue. This exhibits the possibility of combating the basic limitations of cell therapy, including ineffective stem cell implantation and the ability to induce the migration of endogenous stem cells to the ischemic cardiac tissue and promote heart repair.

Injectable Self‐Oxygenating Cardio‐Protective and Tissue Adhesive Silk‐Based Hydrogel for Alleviating Ischemia After Mi Injury

“…Previously, endogenous SDF levels after MI in rat and pig cardiac tissue were shown to fall to considerably lower levels and decrease to less than half the concentration 24 h post-MI. [102,103] However, the exogenous introduction of SDF raised the SDF levels by 25% at the pericardium. [103] Additionally, encapsulating SDF within hydrogels and microspheres has been shown to increase its stability and bioavailability over several weeks.…”

“…[102,103] However, the exogenous introduction of SDF raised the SDF levels by 25% at the pericardium. [103] Additionally, encapsulating SDF within hydrogels and microspheres has been shown to increase its stability and bioavailability over several weeks. [94,103] In another study, the positive effects of exogenous SDF as a cardioprotective chemokine have been shown to rapidly up-regulate and persist for 7 days in the infarct and peri-infarct zones, thereby acting as a gradient-guided homing beacon to facilitate recruitment and adhesion of progenitor cells to the infarct border zone.…”

“…[103] Additionally, encapsulating SDF within hydrogels and microspheres has been shown to increase its stability and bioavailability over several weeks. [94,103] In another study, the positive effects of exogenous SDF as a cardioprotective chemokine have been shown to rapidly up-regulate and persist for 7 days in the infarct and peri-infarct zones, thereby acting as a gradient-guided homing beacon to facilitate recruitment and adhesion of progenitor cells to the infarct border zone. [104] Based on these studies, we anticipate the release, and hence, the cardioprotective effects of SDF in the conjugated TSF gels may be observed over a few weeks, as evident from Figure 6A(vi),H. More importantly, the exogenous SDF levels were higher at the implantation site (infarct area) than the endogenous SDF levels in the healthier regions (Figure S6, Supporting Information).…”