A novel method for objectively, rapidly and accurately evaluating burn depth via near infrared spectroscopy.

The accurate and objective evaluation of burn depth is a significant challenge in burn wound care. Herein, we used near infrared spectroscopy (NIRS) technology to measure the different depth of thermal burns in ex vivo porcine models. Based on the intensity of the spectral signals and the diffuse reflection theory, we extracted the optical parameters involved in functional (total hemoglobin and water content) and structural (tissue scattered size and scattered particles) features that reflect the changes in burn depth. Next, we applied support vector regression to construct a model including the optical property parameters and the burn depth. Finally, we histologically verified the burn depth data collected via NIRS. The results showed that our inversion model could achieve an average relative error of about 7.63%, while the NIRS technology diagnostic accuracy was in the range of 50 µm. For the first time, this novel technique provides physicians with real-time burn depth information objectively and accurately.

Exosomes of adult human fibroblasts cultured on 3D silk fibroin nonwovens intensely stimulate neoangiogenesis.

BACKGROUND: Bombyx mori silk fibroin is a biomacromolecule that allows the assembly of scaffolds for tissue engineering and regeneration purposes due to its cellular adhesiveness, high biocompatibility and low immunogenicity. Earlier work showed that two types of 3D silk fibroin nonwovens (3D-SFnws) implanted into mouse subcutaneous tissue were promptly vascularized via undefined molecular mechanisms. The present study used nontumorigenic adult human dermal fibroblasts (HDFs) adhering to a third type of 3D-SFnws to assess whether HDFs release exosomes whose contents promote neoangiogenesis. METHODS: Electron microscopy imaging and physical tests defined the features of the novel carded/hydroentangled 3D-SFnws. HDFs were cultured on 3D-SFnws and polystyrene plates in an exosome-depleted medium. DNA amounts and D-glucose consumption revealed the growth and metabolic activities of HDFs on 3D-SFnws. CD9-expressing total exosome fractions were from conditioned media of 3D-SFnws and 2D polystyrene plates HDF cultures. Angiogenic growth factors (AGFs) in equal amounts of the two groups of exosomal proteins were analysed via double-antibody arrays. A tube formation assay using human dermal microvascular endothelial cells (HDMVECs) was used to evaluate the exosomes' angiogenic power. RESULTS: The novel features of the 3D-SFnws met the biomechanical requirements typical of human soft tissues. By experimental day 15, 3D-SFnws-adhering HDFs had increased 4.5-fold in numbers and metabolized 5.4-fold more D-glucose than at day 3 in vitro. Compared to polystyrene-stuck HDFs, exosomes from 3D-SFnws-adhering HDFs carried significantly higher amounts of AGFs, such as interleukin (IL)-1α, IL-4 and IL-8; angiopoietin-1 and angiopoietin-2; angiopoietin-1 receptor (or Tie-2); growth-regulated oncogene (GRO)-α, GRO-ß and GRO-γ; matrix metalloproteinase-1; tissue inhibitor metalloproteinase-1; and urokinase-type plasminogen activator surface receptor, but lesser amounts of anti-angiogenic tissue inhibitor metalloproteinase-2 and pro-inflammatory monocyte chemoattractant protein-1. At concentrations from 0.62 to 10 µg/ml, the exosomes from 3D-SFnws-cultured HDFs proved their angiogenic power by inducing HDMVECs to form significant amounts of tubes in vitro. CONCLUSIONS: The structural and mechanical properties of carded/hydroentangled 3D-SFnws proved their suitability for tissue engineering and regeneration applications. Consistent with our hypothesis, 3D-SFnws-adhering HDFs released exosomes carrying several AGFs that induced HDMVECs to promptly assemble vascular tubes in vitro. Hence, we posit that once implanted in vivo, the 3D-SFnws/HDFs interactions could promote the vascularization and repair of extended skin wounds due to burns or other noxious agents in human and veterinary clinical settings.

Corrigendum to: 'Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration'.

[This corrects the article DOI: 10.1186/s41038-019-0178-8.].

Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration.

Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types, growth factors, extracellular matrix (ECM), nerves, and blood vessels. Mesenchymal stromal cells (MSCs) take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans. Exosomes, which are among the key products MSCs release, mimic the effects of parental MSCs. They can shuttle various effector proteins, messenger RNA (mRNA) and microRNAs (miRNAs) to modulate the activity of recipient cells, playing important roles in wound healing. Moreover, using exosomes avoids many risks associated with cell transplantation. Therefore, as a novel type of cell-free therapy, MSC-exosome -mediated administration may be safer and more efficient than whole cell. In this review, we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration. In addition, we address the hypothesis of MSCs microenvironment extracellular vesicles (MSCs-MEVs) or MSCs microenvironment exosomes (MSCs-MExos) that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications. This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.

Targeting Human Astrocytes' Calcium-sensing Receptors for Treatment of Alzheimer's Disease.

Understanding the pathophysiology of Alzheimer's disease (AD) in the principal human neural cells is necessary for finding therapeutics for this illness. To help do this, we have been using freshly cultured functionally normal cerebral cortical adult human astrocytes (NAHAs) and postnatal neurons. The findings show that amyloid-ß oligomers (Aß-os) binding to calcium-sensing receptors (CaSRs) on NAHAs and neuron surfaces trigger signals capable of driving AD pathogenesis. This Aß•CaSR signalling shifts the amyloid precursor protein (APP) from its α-secretase shedding producing neurotrophic/neuroprotective soluble (s)APPα to its ß-secretase cleaving engendering AD-driving Aß42/Aß42-os peptides. Aß•CaSR signalling in NAHAs also drives the release of toxic hyper-phosphorylated Tau proteins in exosomes, and of nitric oxide, and VEGF-A. These several harmful agents comprise the neuron-killing machinery, driving the very slowly spreading AD neurocontagion. VEGF-A over-secretion from Aß-exposed blood vessel-attached astrocytes induces a functional magnetic resonance imaging- detectable hippocampal neoangiogenesis which indicates approaching AD in amnestic minor cognitive impairment (aMCI) patients. Most important in AD's regard, selective allosteric CaSR antagonists (calcylitics) added to Aß42/Aß42-os-exposed NAHAs (or to human neuron cultures) rescue the extracellular shedding of neurotrophic/ neuroprotective sAPPα and suppress all the neurotoxic effects of Aß•CaSR signalling even when multiple microglial cytokines are also present. Therefore, since the multipotent calcilytics would be reasonably safe and inexpensive drugs for humans, it is worthwhile testing them as AD therapeutics in clinical trials especially in persons in the earliest detectable stages of AD neuropathology progression such as aMCI.