Phytochemicals as new therapeutic candidates simultaneously stimulate proliferation and counteract senescence of stem cells.

Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapy. However, the research and clinical application of MSCs are greatly hindered by the limited cells proliferation and replicative senescence. Therapeutic agents that can both enhance the proliferative ability and decrease the replicative senescence of MSCs are greatly needed, however, not been reported yet. Herein, for the first time, we identified 11 natural compounds from medicinal plants with both excellent proliferative and anti-senescence abilities in MSCs. The qPCR analysis indicated underlying mechanisms associated with fibroblast growth factor, transforming growth factor, Wnt/ß-catenin and leukemia-induced factor in proliferation; the reactive oxygen species production, mitochondrial dysfunction autophagy and proteostasis are involved in cells senescence-related mechanism. Phytochemicals are demonstrated as novel therapeutic candidates with promising effects in both stimulating proliferation and retarding replicative senescence of stem cells with high safety.

Self-powered smart patch promotes skin nerve regeneration and sensation restoration by delivering biological-electrical signals in program.

Skin wound is always accompanied with nerve destruction. Due to the limited clinical treatment option, loss of skin sensation with unsatisfactory nerve regeneration is remained to be a challenge for wound therapy. Endogenous mesenchymal stem cells (MSCs) based in situ regeneration, of which, MSCs recruited by chemokines and directed for neuronal differentiation by biological and electrical signals have been thought a novel strategy with potential to accelerate the nerve regeneration and sensory functions recovery. However, most current therapeutic systems usually deliver the chemokines, biological and electrical signals separately and statically, resulting in limited nerve regeneration and sensory functions recovery. Moreover, most of the devices for providing electrical signals need external energy input and complicated practice, leading to poor compliance in patients. To address these issues, we propose a self-powered smart patch (PRG-G-C) to provide chemokine and biological-electrical cues in program. PRG-G-C was composed of a flexible piezoelectric generator to supply electrical stimulation and a conductive gel, which served as the reservoir of chemokine and neural directing exosomes as well as the electrode to transfer electric cue. PRG-G-C was shown to efficiently accelerate rapid nerve regeneration and sensation restoration at the wound site within 23 days. This study demonstrates a proof-to-concept in organizing chemokine, neural directing biological-electrical heterogeneous cues within a self-powered smart patch for accelarating nerve regeneration and sensation restoration, possessing great potential in neural repair applications.

Plant Exosomes As Novel Nanoplatforms for MicroRNA Transfer Stimulate Neural Differentiation of Stem Cells In Vitro and In Vivo.

Differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into functional neural cells has been widely investigated for treating neural diseases. However, the limited neural differentiation of BMSCs remains a big challenge to overcome. Herein, for the first time, ginseng-derived exosomes (G-Exos) were demonstrated to have excellent efficiency in stimulating the neural differentiation of BMSCs by transferring the incorporated miRNAs to BMSCs efficiently. In vivo, a photo-cross-linkable hydrogel with chemokine and G-Exos loaded shows strong efficacy in recruiting and directing the neural differentiation of BMSCs in the program. G-Exos were demonstrated to be promising nanoplatforms in transferring plant-derived miRNAs to mammalian stem cells for neural differentiation both in vitro and in vivo, possessing great potential in neural regenerative medicine.

Smart graphene-based hydrogel promotes recruitment and neural-like differentiation of bone marrow derived mesenchymal stem cells in rat skin.

Strategies to direct the differentiation of endogenous bone marrow derived mesenchymal stem cells (BMSCs) in vivo following recruitment to the injured site are critical to realizing the potential of stem cell-based therapies. But the differentiation efficiency of BMSCs remains limited without direction. Here we demonstrated a novel strategy to promote neuronal differentiation of BMSCs using cross-linked polyethylenimine (PEI) grafted graphene oxide (GO) as the enzyme responsive vector for delivering active genes to BMSCs. In vivo, a core-shell microfiber arrayed hydrogel with a chemokine (SDF-1α) and the cross-linked GO-PEI/pDNAs-bFGF microparticles incorporated into the shell and core, respectively, were constructed. The arrayed hydrogel was shown to recruit and stimulate the neural-like differentiation of BMSCs effectively by delivering the CXCL12 and GO-PEI/pDNAs-bFGF in a self-controlled manner. With this strategy, both in vitro and in vivo neuronal differentiation of BMSCs with function were accelerated significantly. The cross-linked GO-PEI mediated gene transfection together with a multi-functional microfiber arrayed hydrogel provide a translatable approach for endogenous stem cell-based regenerative therapy.

The crude ethanol extract of Periplaneta americana L. stimulates wound healing in vitro & in vivo.

Periplaneta americana L. is a Traditional Chinese Medicine that has been used in clinic treatment of various diseases for a long history. However, the therapeutic potential and the underlying mechanism of Periplaneta americana L. in the skin wound therapy was not investigated comprehensively yet. This study aims to investigate the influence of the crude ethanol extract of PAL in the different wound stages including: (1) the migration and chemotaxis to skin cells in the first stage; (2) proliferation and cells cycle of skin cells in the second stage; (3) remodeling effect and secretion of growth factors, collagens in the third stage; (4) as well as the influence in the blood vessels regeneration in the late stage. The crude ethanol extract of PAL was shown to (1) promote the keratinocytes proliferation and regulate the cells cycle of fibroblasts significantly; (2) stimulate the migration of keratinocytes and fibroblasts obviously; (3) enhance the EGF and VEGF secretion both in vitro & in vivo; (4) accelerate the wound healing, collagen synthesis and angiogenesis. The crude ethanol extract of KFX was shown a promising therapeutic agent for the wound therapy with great efficacy to accelerate the wound healing with improved quality.

Construction of a biomimetic chemokine reservoir stimulates rapid in situ wound repair and regeneration.

Skin is the first protection of human body. It is always challenged by a range of external factors, resulting in the wounds of skin. Hydrogel, as a dressing with multiple advantages, causes increasing interests or the applications in wound treatment. However, the function and importance of micro-environment of wound region are frequently neglected. In this study, we successfully developed a chemokine loaded biomimetic hydrogel as a functional reservoir to stimulate the rapid in situ recruitment of BMSCs for fast wound repair and regeneration. The biomimetic hydrogel was fabricated by using the Polyvinyl alcohol (PVA) combined with chitosan (CS) as the hybrid materials. The fabricated hydrogel possesses many features such as the porous structure, high swelling rate and moisture retention property. More importantly, the incorporated chemokine could be released with a sustained manner from the hydrogel and recruited the bone marrow mesenchymal stem cells (BMSCs) significantly both in vitro & in vivo. Moreover, the hydrogel was demonstrated to be highly biocompatible to the skin tissue without any side effect or irritation observed. Topical delivery of chemokine by the biomimetic PVA/CS hybrid material based hydrogel is demonstrated as a promising carrier to accelerate wound repair and regeneration without inducing scar formation and any other negative complications. The PVA/CS/SDF-1 hydrogel was shown a novel therapeutic system for wound therapy.

Periplaneta Americana L. as a novel therapeutics accelerates wound repair and regeneration.

Kangfuxin (KFX) is the ethanol extract of Periplaneta Americana L., which has been widely used in Traditional Chinese Medicine for the treatment of injury in clinic with a long history. However, the biological influence of KFX in the different wound stages was not investigated comprehensively yet. This study aims to investigate the influence of KFX in the various wound healing activities with cellular and animal models, including the influence of KFX in 1) proliferation and cells cycle of kerationcytes and fibroblasts; 2) migration and chemotaxis of these skin cells; 3) secretion of EGF and VEGF; 4) the healing rate; 5) synthesis and deposition of different types of collagen; 6) as well as the pro-angiogenesis effect. KFX was shown to/for 1) promote the kerationcytes proliferation and regulate the cells cycle of skin fibroblasts significantly; 2) obviously stimulate the migration of kerationcytes and chemotaxis of fibroblasts; 3) the trend to promote EGF and VEGF secretion both in vitro & in vivo; 4) accelerate the wound closure, collagen synthesis and angiogenesis. KFX was demonstrated to accelerate wound healing and improve the healing quality by multiple regulation. Results of this study provide the comprehensive evidence for the application of KFX as a novel therapeutics for wound treatment.