Ginsenoside RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells on radiation induced intestinal injury.

Content and aims: Ginsenoside RG1 (RG1) is thought to enhance proliferation and differentiation of stem cell, however, its role on paracrine efficacy of stem cell remains unclear. Here we examined if and how RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) on radiation induced intestinal injury (RIII). METHOD: Irradiated rats randomly received intraperitoneal injection of conditioned medium (CM) derived from non-activated BM-MSCs (MSC-CM) or BM-MSCs pre-activated by RG-1 (RG1-MSC-CM). Intestinal samples were collected, followed by the evaluation of histological and functional change, apoptosis, proliferation, inflammation, angiogenesis and stem cell regeneration. The effects of heme oxygenase-1 (HO-1) were investigated using HO-1 inhibitor or siRNA. RESULT: RG1 enhanced the paracrine efficacy of BM-MSCs partially through upregulation of HO-1. RG1-MSC-CM rather than MSC-CM significantly improved the survival and intestinal damage of irradiated rats via improvement of intestinal proliferation/apoptosis, inflammation, angiogenesis and stem cell regeneration in a HO-1 dependent mechanism. The mechanism for the superior paracrine efficacy of RG1-MSC-CM is related to a higher release of two pivotal cytokines VEGF and IL-6. CONCLUSION: Our study revealed that RG1 enhances paracrine effects of BM-MSCs on RIII, providing a novel method for maximizing the paracrine potential of MSCs.

Prolyl hydroxylase 2 silencing enhances the paracrine effects of mesenchymal stem cells on necrotizing enterocolitis in an NF-κB-dependent mechanism.

Treatment options for necrotizing enterocolitis (NEC) remain inadequate. Here we examined if and how prolyl hydroxylase 2 (PHD2) silencing enhances the paracrine effects of bone-marrow-derived mesenchymal stem cells (BM-MSCs) on NEC. In this study, BM-MSCs were transduced with lentiviruses containing GFP (GFP-MSC) or shPHD2-GFP constructs (PHDMSC), followed by intraperitoneal injection of the PHDMSC-conditioned medium (PHDMSC-CM) or the GFP-MSC-conditioned medium (MSC-CM) into a rat pup model of NEC. Our results showed that systemic infusion of PHDMSC-CM, but not MSC-CM, significantly improved intestinal damage and survival of NEC rats. Such benefits may involve the modulation of epithelial regeneration and inflammation, as indicated by the regeneration of intestinal epithelial/stem cells, the regulation of Treg cells function and pro-/anti-inflammatory cytokine balance. The mechanism for the superior paracrine efficacy of PHDMSC is related to a higher release of pivotal factor IGF-1 and TGF-ß2. NF-κB activation was induced by PHD2 silencing to induce IGF-1 and TGF-ß2 secretion via binding to IGF-1 and TGF-ß2 gene promoter. Our work indicated that PHD2 silencing enhanced the paracrine effect of BM-MSCs on NEC via the NF-κB-dependent mechanism which may be a novel strategy for stem cell therapy on NEC.

Immediate and late outcomes of stenting for severe extracranial internal carotid artery stenosis in octogenarian patients.

Background: Multiple studies suggest that internal carotid artery stenting can be performed safely in octogenarians with low periprocedural complication rates. However, great concern still exists as to whether these patients will gain long-term benefits from this procedure given their advanced age and uncertain life expectancy. We decided to conduct a retrospective study to determine short-and long-term clinical outcomes and to analyze survival duration in this population. Methods and Results: Sixty-nine consecutive elderly patients with either symptomatic or asymptomatic stenosis ≥70% underwent 86 procedures. Immediate and late outcomes, as well as survival data, were analyzed retrospectively. Mean age was 83.1 ± 2.7 years. Mean survival was 49.3 ± 10.1 months. A complete neurological assessment was obtained at 1 and 2 years in 100% of patients, at 3 years in 90.7% of patients and at 5 years in 84.8% of patients. Two major and one minor ischemic strokes occurred during the periprocedural period. No death, myocardial infarction or intracranial hemorrhage was recorded. The mean follow-up period was 55.4 ± 24.6 months. Four patients experienced a minimum of 1 year of follow-up, and the longest is 8 years. Among the patients with the longest follow-up time, 6 had ischemic strokes, of which 2 were fatal. In total, 17 deaths occurred. Four patients experienced dementia without stroke. Survival at 3 and 5 years was estimated to be 90% and 73%, respectively. Conclusion: This study demonstrated that stenting in octogenarians was safe and effective during the periprocedural period. Long-term follow-up showed a low rate of fatal and nonfatal stroke, and patients survived long enough to benefit from the procedure. However, it was associated with a relatively high rate of long-term event. Though carotid artery stenting is a minimally invasive procedure, it should still be performed with great caution and only in carefully selected patients. The present study suggested that in this age population, carotid artery stenting might be considered as a revascularization option.