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Adipose-Derived Mesenchymal Stromal Cells in Regenerative Medicine: State of Play, Current Clinical Trials, and Future Prospects.

ABSTRACT: Significance: Wound healing is a complex process involving pain and inflammation, where innervation plays a central role. Managing wound healing and pain remains an important issue, especially in pathologies such as excessive scarring (often leading to fibrosis) or deficient healing, leading to chronic wounds. Recent Advances: Advances in therapies using mesenchymal stromal cells offer new insights for treating indications that previously lacked options. Adipose-derived mesenchymal stromal cells (AD-MSCs) are now being used to a much greater extent in clinical trials for regenerative medicine. However, to be really valid, these randomized trials must imperatively follow strict guidelines such as consolidated standards of reporting trials (CONSORT) statement. Indeed, AD-MSCs, because of their paracrine activities and multipotency, have potential to cure degenerative and/or inflammatory diseases. Combined with their relatively easy access (from adipose tissue) and proliferation capacity, AD-MSCs represent an excellent candidate for allogeneic treatments. Critical Issues: The success of AD-MSC therapy may depend on the robustness of the biological functions of AD-MSCs, which requires controlling source heterogeneity and production processes, and development of biomarkers that predict desired responses. Several studies have investigated the effect of AD-MSCs on innervation, wound repair, or pain management separately, but systematic evaluation of how those effects could be combined is lacking. Future Directions: Future studies that explore how AD-MSC therapy can be used to treat difficult-to-heal wounds, underlining the need to thoroughly characterize the cells used, and standardization of preparation processes are needed. Finally, how this a priori easy-to-use cell therapy treatment fits into clinical management of pain, improvement of tissue healing, and patient quality of life, all need to be explored.

SUBMITTER: Laloze J

PROVIDER: S-EPMC7698876 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In recent decades, research on the therapeutic potential of progenitor cells has advanced considerably. Among progenitor cells, mesenchymal stromal cells (MSCs) have attracted significant interest and have proven to be a promising tool for regenerative medicine. MSCs are isolated from various anatomical sites, including bone marrow, adipose tissue, and umbilical cord. Advances in separation, culture, and expansion techniques for MSCs have enabled their large-scale therapeutic application. This progress accompanied by the rapid improvement of transplantation practices has enhanced the utilization of MSCs in regenerative medicine. During tissue healing, MSCs may exhibit several therapeutic functions to support the repair and regeneration of injured tissue. The process underlying these effects likely involves the migration and homing of MSCs, as well as their immunotropic functions. The direct differentiation of MSCs as a cell replacement therapeutic mechanism is discussed. The fate and behavior of MSCs are further regulated by their microenvironment, which may consequently influence their repair potential. A paracrine pathway based on the release of different messengers, including regulatory factors, chemokines, cytokines, growth factors, and nucleic acids that can be secreted or packaged into extracellular vesicles, is also implicated in the therapeutic properties of MSCs. In this review, we will discuss relevant outcomes regarding the properties and roles of MSCs during tissue repair and regeneration. We will critically examine the influence of the local microenvironment, especially immunological and inflammatory signals, as well as the mechanisms underlying these therapeutic effects. Importantly, we will describe the interactions of local progenitor and immune cells with MSCs and their modulation during tissue injury. We will also highlight the crucial role of paracrine pathways, including the role of extracellular vesicles, in this healing process. Moreover, we will discuss the therapeutic potential of MSCs and MSC-derived extracellular vesicles in the treatment of COVID-19 (coronavirus disease 2019) patients. Overall, this review will provide a better understanding of MSC-based therapies as a novel immunoregenerative strategy.

Project description:Background and objectiveNeuroblastoma (NB) is a common malignant tumor in children, and its treatment remains challenging. Precision medicine, as an individualized treatment strategy, aims to improve efficacy and reduce toxicity by combining unique patient- and tumor-related factors, bringing new hope for NB treatment. In this article, we review the evidence related to precision medicine in NB, with a focus on potential clinically actionable targets and a series of targeted drugs associated with NB.MethodsWe conducted an extensive search in PubMed, EMBASE, and Web of Science using key terms and database-specific strategies, filtered for time and language, to ensure a comprehensive collection of literature related to precision medicine in NB. The main search terms consisted of "neuroblastoma", "precision medicine", "pediatrics", and "targeting". The articles included in this study encompass those published from 1985 to the present, without restrictions on the type of articles.Key content and findingsALK inhibitors and MYCN inhibitors have been developed to interfere with tumor cell growth and dissemination, thereby improving treatment outcomes. Additionally, systematic testing to identify relevant driver mutations is crucial and can be used for diagnosis and prognostic assessment through the detection of many associated molecular markers. Furthermore, liquid biopsy, a non-invasive tumor detection method, can complement tissue biopsy and play a role in NB by analyzing circulating tumor DNA and circulating tumor cells to provide genetic information and molecular characteristics of the tumor. Recently, trials conducted by many pediatric oncology groups have shown the urgent need for new approaches to cure relapsed and refractory patients.ConclusionsThe purpose of this review is to summarize the latest advances in clinical treatment of NB, to better understand and focus on the development of promising treatment approaches, and to expedite the transition to the precision medicine clinical relevance in NB patients.

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Adipose-Derived Mesenchymal Stromal Cells in Regenerative Medicine: State of Play, Current Clinical Trials, and Future Prospects.

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