Multiple-therapy strategies via polysaccharides-based Nano-Systems in fighting Cancer

Severe psoriasis, a chronic inflammatory skin disease is increasingly being effectively managed by targeted immunotherapy but long-term immunotherapy poses health risk and loss of response. Therefore, there is a need for alternative therapy strategies. Mesenchymal stem/stromal cell (MSC) exosomes are widely known for their potent immunomodulatory properties. Here we investigated if topically applied MSC exosomes could alleviate psoriasis-associated inflammation. Topically applied fluorescent exosomes on human skin explants were confined primarily to the stratum corneum with <1% input fluorescence exiting the explant over a 24-h period. Nevertheless, topically applied MSC exosomes in a mouse model of imiquimod (IMQ) psoriasis significantly reduced IL-17 and terminal complement activation complex C5b-9 in the mouse skin. MSC exosomes were previously shown to inhibit complement activation, specifically C5b-9 complex formation through CD59. Infiltration of neutrophils into the stratum corneum is characteristic of psoriasis and neutrophils are a major cellular source of IL-17 in psoriasis through the release of neutrophil extracellular traps (NETs). We propose that topically applied MSC exosomes inhibit complement activation in the stratum corneum and this alleviates IL-17 release by NETS from neutrophils that accumulate in and beneath the stratum corneum.

Download Full-text

Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

Antibiotics ◽

10.3390/antibiotics10070750 ◽

2021 ◽

Vol 10 (7) ◽

pp. 750

Author(s):

Pasquale Marrazzo ◽

Valeria Pizzuti ◽

Silvia Zia ◽

Azzurra Sargenti ◽

Daniele Gazzola ◽

...

Keyword(s):

Stem Cells ◽

Defense Mechanisms ◽

Live Cells ◽

Label Free ◽

Bacterial Diseases ◽

Prospective Application ◽

Therapy Strategies ◽

Stromal Stem Cells ◽

Different Sources

Antibiotic resistance is creating enormous attention on the development of new antibiotic-free therapy strategies for bacterial diseases. Mesenchymal stromal stem cells (MSCs) are the most promising candidates in current clinical trials and included in several cell-therapy protocols. Together with the well-known immunomodulatory and regenerative potential of the MSC secretome, these cells have shown direct and indirect anti-bacterial effects. However, the low reproducibility and standardization of MSCs from different sources are the current limitations prior to the purification of cell-free secreted antimicrobial peptides and exosomes. In order to improve MSC characterization, novel label-free functional tests, evaluating the biophysical properties of the cells, will be advantageous for their cell profiling, population sorting, and quality control. We discuss the potential of emerging microfluidic technologies providing new insights into density, shape, and size of live cells, starting from heterogeneous or 3D cultured samples. The prospective application of these technologies to studying MSC populations may contribute to developing new biopharmaceutical strategies with a view to naturally overcoming bacterial defense mechanisms.

Download Full-text

Stem Cells and Gene Therapy in Progressive Hearing Loss: the State of the Art

Journal of the Association for Research in Otolaryngology ◽

10.1007/s10162-020-00781-0 ◽

2021 ◽

Author(s):

Aida Nourbakhsh ◽

Brett M. Colbert ◽

Eric Nisenbaum ◽

Aziz El-Amraoui ◽

Derek M. Dykxhoorn ◽

...

Keyword(s):

Stem Cells ◽

Gene Therapy ◽

Hearing Loss ◽

Treatment Modalities ◽

Versus Gene ◽

Vitro Model ◽

New Treatment ◽

Induced Pluripotent ◽

Therapy Strategies

AbstractProgressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.

Download Full-text

Ocular growth and metabolomics are dependent upon the spectral content of ambient white light

Scientific Reports ◽

10.1038/s41598-021-87201-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Raymond P. Najjar ◽

Juan Manuel Chao De La Barca ◽

Veluchamy A. Barathi ◽

Candice Ee Hua Ho ◽

Jing Zhan Lock ◽

...

Keyword(s):

Critical Role ◽

Spectral Composition ◽

Light Therapy ◽

World Population ◽

Spectral Content ◽

Ocular Growth ◽

Nitric Oxide Metabolism ◽

Therapy Strategies ◽

Indoor Lighting ◽

The Impact

AbstractMyopia results from an excessive axial growth of the eye, causing abnormal projection of remote images in front of the retina. Without adequate interventions, myopia is forecasted to affect 50% of the world population by 2050. Exposure to outdoor light plays a critical role in preventing myopia in children, possibly through the brightness and blue-shifted spectral composition of sunlight, which lacks in artificial indoor lighting. Here, we evaluated the impact of moderate levels of ambient standard white (SW: 233.1 lux, 3900 K) and blue-enriched white (BEW: 223.8 lux, 9700 K) lights on ocular growth and metabolomics in a chicken-model of form-deprivation myopia. Compared to SW light, BEW light decreased aberrant ocular axial elongation and accelerated recovery from form-deprivation. Furthermore, the metabolomic profiles in the vitreous and retinas of recovering form-deprived eyes were distinct from control eyes and were dependent on the spectral content of ambient light. For instance, exposure to BEW light was associated with deep lipid remodeling and metabolic changes related to energy production, cell proliferation, collagen turnover and nitric oxide metabolism. This study provides new insight on light-dependent modulations in ocular growth and metabolomics. If replicable in humans, our findings open new potential avenues for spectrally-tailored light-therapy strategies for myopia.

Download Full-text