Intramyocardial delivery of human cardiac stem cell spheroids with enhanced cell engraftment ability and cardiomyogenic potential for myocardial infarct repair.

Strategies for stem cell-based cardiac regeneration and repair are key issues for the ischemic heart disease (IHD) patients with chronic complications related to ischemic necrosis. Cardiac stem cells (CSCs) have demonstrated high therapeutic efficacy for IHD treatment owing to their specific cardiac-lineage commitment. The therapeutic potential of CSCs could be further enhanced by designing a cellular spheroid formulation. The spheroid culture condition of CSCs was optimized to ensure regulated size and minimal core necrosis in the spheroids. The CSC spheroids revealed mRNA profiles of the factors related to cardiac regeneration, angiogenesis, anti-inflammatory, and cardiomyocyte differentiation with a higher expression level than the CSCs. Intramyocardially delivered CSC spheroids in the rat IHD model resulted in a significant increase in retention rate by 1.82-fold (day 3) and 1.98-fold (day 14) compared to CSCs. Endothelial cell differentiation and neovascularization of the engrafted CSC spheroids were noted in the infarcted myocardium. CSC spheroids significantly promoted cardiac regeneration: i.e., decreased infarction and fibrotic area (11.22% and 4.18%) and increased left ventricle thickness (0.62 mm) compared to the untreated group. Cardiac performance was also improved by 2.04-fold and 1.44-fold increase in the ejection fraction and fractional shortening, respectively. Intramyocardial administration of CSC spheroids might serve as an advanced therapeutic modality with enhanced cell engraftment and regenerative abilities for cardiac repair after myocardial infarction.

The effect of antioxidant and whitening action on Plantago asiatica L. leaf ethanol extract for health care.

BACKGROUND: The Plantago asiatica L. is easy to cultivate and has been used as a folk remedy since ancient times because of various pharmacological actions such as anti-inflammation and antioxidation. It also contains a variety of flavonoids such as aucubin, which is thought to be excellent for whitening, antioxidant and anti-inflammatory action. OBJECTIVE: We investigated the effect of P. asiatica L. leaf ethanol extracts containing various active ingredients on antioxidative, anti-inflammation and whitening action and investigated its potential as a health care material. P. asiatica L. has been widely used in folk remedies. RESULTS: The cell toxicity test using RAW264.7 cells showed a high cell survival rate of over 75%, thus demonstrating the safety of the sample. In order to study the antioxidant activity of P. asiatica L. leaf ethanol extracts, we studied a sample which showed radical scavenging activity in a dose-dependent manner. To observe the antioxidant activity at the cell level, RAW 264.7 cells were used and inhibition of ROS production was measured. The ROS production was suppressed in a dose-dependent manner and the scavenging activity was stronger than the sample's own radical scavenging ability. To observe the anti-inflammatory effect of P. asiatica L. leaf ethanol extracts, inhibition of NO generation was observed using LPS-induced RAW 264.7 cells. NO generation was inhibited in a dose-dependent manner and was strongly inhibited by 31% at 100 µg/mL. In vitro, L-DOPA and L-tyrosine were used to inhibit tyrosinase action in a dose-dependent manner. The concentration of melanin at 1, 10, and 100 µg/mL was suppressed in B16 F10 melanin cells supplemented with α-MSH in the cells, and the inhibition was suppressed to 29% at 100 µg/mL. In the B16 F10 melanin cell stimulated with MSH, the P. asiatica L. leaf ethanol extracts inhibited melanin formation in a dose-dependent manner. CONCLUSION: P. asiatica L. leaf ethanol extracts are expected to be developed as whitening cosmeceutical ingredients and as health care ingredients with antioxidant and anti-inflammatory properties.

Intra-articular delivery of synovium-resident mesenchymal stem cells via BMP-7-loaded fibrous PLGA scaffolds for cartilage repair.

Delivery of synovium-resident mesenchymal stem cells (synMSCs) to cartilage defect site might provide a novel therapeutic modality for treatment of articular cartilage diseases. However, low isolation efficiency of synMSCs limits their therapeutic application. Niche-preserving non-enzymatic isolation of synMSCs was firstly attempted by employing micro-organ culture system based on recapitulating tissue-specific homeostasis ex vivo. The isolated synMSCs retained superior long-term growth competency, proliferation and chondrogenic potential to bone marrow-derived MSCs (BMSCs). It was noted that synMSCs demonstrated 9-fold increase in cartilaginous micro-tissue formation and 13-fold increase in sulfated proteoglycans deposition compared to BMSCs. For delivery of synMSCs, fibrous PLGA scaffolds were specifically designed for full-thickness osteochondral defects in rabbits. The scaffolds provided effective micro-environment for growth and host-integration of synMSCs. Combined delivery of synMSCs with bone morphogenetic proteins-7 (BMP-7) was designed to achieve synergistic therapeutic efficacy. BMP-7-loaded PLGA nanoparticles electrosprayed onto the scaffolds released BMP-7 over 2 weeks to conform with its aimed role in stimulating early stage endochondral ossification. Scaffold-supported combined administration of synMSCs with BMP-7 resulted in high proteoglycan and collagen type II induction and thick hyaline cartilage formation. Intra-articular co-delivery of synMSCs with BMP-7 via fibrous PLGA scaffolds may be a promising therapeutic modality for articular cartilage repair.