Exosomes, as therapeutically relevant cell-secreted extracellular vesicles, have attracted enormous interest because they participate in intercellular communication and facilitate wound healing. Stem cell-derived exosomes exhibit similar biological effects to source cells with the exception of low immunogenicity and no tumorigenicity, as well as superior efficacy in promoting wound healing. Exosomes accelerate wound healing by promoting angiogenesis and cell proliferation, as well as balancing inflammatory responses. Particularly, when exosomes are genetically modified or used in combination with materials, they can exhibit better comprehensive therapeutic properties, such as enriching active ingredients, targeted delivery, and physiological barrier to penetration, which are not available in traditional single products. Besides, exosomes have also been considered for diagnostic and therapeutic uses related to wounds, such as repairing complex wounds, enhancing graft success, treating related complications, and serving as diagnostic biomarkers. However, their clinical applications still face challenges, as reliable commercial products are not yet available. This review will focus on recent research advances that describe the characteristics and isolation of exosomes, introduce the sources of exosomes suitable for wound repair and related complications, illustrate the value of engineered exosomes and their development directions in the future, and provide evidence for the potential therapeutic application of exosomes in wound healing, as well as discuss potential risks, challenges, and solutions for future applications.

Exosomes and Their Bioengineering Strategies in the Cutaneous Wound Healing and Related Complications: Current Knowledge and Future Perspectives

Severe injuries or diseases affecting the peripheral and central nervous systems can result in impaired organ function and permanent paralysis.Conventional interventions, such as drug administration and cell-based therapy, exhibit limited effectiveness due to their inability to preserve post-implantation cell survival and impede the deterioration of adjacent tissues.Exosomes have recently emerged as powerful tools for tissue repair owing to their proteins and nucleic acids, as well as their unique phospholipid properties, which facilitate targeted delivery to recipient cells.Engineering exosomes, obtained by manipulating the parental cells or directly functionalizing exosomes, play critical roles in enhancing regenerative repair, reducing inflammation, and maintaining physiological homeostasis.Furthermore, exosomes have been shown to restore neurological function when used in combination with biomaterials.This paper primarily focuses on the engineering strategies and delivery routes of exosomes related to neural research and emphasizes the theranostic application of optimized exosomes in peripheral nerve, traumatic spinal cord, and brain injuries.Finally, the prospects of exosomes development and their combination with other approaches will be discussed to enhance our knowledge on their theranostic effectiveness in neurological diseases. 

Engineering strategies and optimized delivery of exosomes for theranostic application in nerve tissue

The COVID-19 pandemic, caused by the rapid global spread of the novel coronavirus (SARS-CoV-2), has caused healthcare systems to collapse and led to hundreds of thousands of deaths. The clinical spectrum of COVID-19 is not only limited to local pneumonia but also represents multiple organ involvement, with potential for systemic complications. One year after the pandemic, pathophysiological knowledge has evolved, and many therapeutic advances have occurred, but mortality rates are still elevated in severe/critical COVID-19 cases. Mesenchymal stromal cells (MSCs) can exert immunomodulatory, antiviral, and pro-regenerative paracrine/endocrine actions and are therefore promising candidates for MSC-based therapies. In this review, we discuss the rationale for MSC-based therapies based on currently available preclinical and clinical evidence of safety, potential efficacy, and mechanisms of action. Finally, we present a critical analysis of the risks, limitations, challenges, and opportunities that place MSC-based products as a therapeutic strategy that may complement the current arsenal against COVID-19 and reduce the pandemic's unmet medical needs.

/pdf/is-there-a-place-for-mesenchymal-stromal-cell-based-422c6tx2j0.pdf

Is there a place for mesenchymal stromal cell-based therapies in the therapeutic armamentarium against COVID-19?

ABSTRACT Introduction Regenerative medicine involves the replacement of damaged cells, tissues, or organs to restore normal function. Mesenchymal stem cells (MSCs) and exosomes secreted by MSCs have unique advantages that make them a suitable candidate in the field of regenerative medicine. Areas covered This article provides a comprehensive overview of regenerative medicine, focusing on the use of MSCs and their exosomes as potential therapies for replacing damaged cells, tissues, or organs. This article discusses the distinct advantages of both MSCs and their secreted exosomes, including their immunomodulatory effects, lack of immunogenicity, and recruitment to damaged areas. While both MSCs and exosomes have these advantages, MSCs also have the unique ability to self-renew and differentiate. This article also assesses the current challenges associated with the application of MSCs and their secreted exosomes in therapy. We have reviewed proposed solutions for improving MSC or exosome therapy, including ex-vivo preconditioning strategies, genetic modification, and encapsulation. Literature search was conducted using Google Scholar and PubMed databases. Expert opinion Providing insight into the future development of MSC and exosome-based therapies and to encourage the scientific community to focus on the identified gaps, develop appropriate guidelines, and enhance the clinical application of these therapies. GRAPHICAL ABSTRACT This graphical abstract illustrates the potential for direct use of MSCs or their secreted exosomes in regenerative medicine, as well as various strategies to enhance their efficacy.

Potential applications of mesenchymal stem cells and their derived exosomes in regenerative medicine

Pulmonary drug delivery has the advantages of being rapid, efficient, and well-targeted, with few systemic side effects. In addition, it is non-invasive and has good patient compliance, making it a highly promising drug delivery mode. However, there have been limited studies on drug delivery via pulmonary inhalation compared with oral and intravenous modes. This paper summarizes the basic research and clinical translation of pulmonary inhalation drug delivery for the treatment of diseases and provides insights into the latest advances in pulmonary drug delivery. The paper discusses the processing methods for pulmonary drug delivery, drug carriers (with a focus on various types of nanoparticles), delivery devices, and applications in pulmonary diseases and treatment of systemic diseases (e.g., COVID-19, inhaled vaccines, diagnosis of the diseases, and diabetes mellitus) with an updated summary of recent research advances. Furthermore, this paper describes the applications and recent progress in pulmonary drug delivery for lung diseases and expands the use of pulmonary drugs for other systemic diseases. 

Pulmonary inhalation for disease treatment: Basic research and clinical translations


 Background: Scientists have been facing numerous challenges in the development of an effective therapeutic strategy for the treatment of COVID-19 pneumonia. Several studies have suggested that improving patient immunity and reducing lung injury induced by SARS-CoV-2 may be effective for treating patients with COVID-19.Methods: A pilot trial of nebulization therapy with exosomes of mesenchymal stem cells (MSCs) was performed on seven patients with COVID-19 pneumonia. Exosomes secreted from MSCs were collected and purified using multiple ultrafiltration steps. All patients were treated with nebulization of MSC-derived exosomes, and primary safety and efficacy outcomes were evaluated.Results: Our clinical study demonstrated that nebulization of MSC-derived exosomes is a novel method that might be utilized in the treatment of COVID-19 pneumonia. Nebulization of MSC-derived exosomes did not induce acute allergic or secondary allergic reactions but did promote the absorption of pulmonary lesions and reduce the time of hospitalization for mild cases of COVID-19 pneumonia.Conclusions: Nebulization of MSC-derived exosomes is a safe, effective, and simple method, and their application at the beginning of treatment may be more beneficial.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000030261. Registered on 26 February 2020.

/pdf/nebulization-therapy-with-umbilical-cord-mesenchymal-stem-1dve6yrfjs.pdf

Nebulization therapy with umbilical cord mesenchymal stem cell-derived exosomes for COVID-19 pneumonia

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Nebulization therapy with umbilical cord mesenchymal stem cell-derived exosomes for COVID-19 pneumonia