A Systematic Review on Extracellular Vesicles-Enriched Fat Grafting: A Shifting Paradigm

Author(s):  
Mohammad Ghiasloo ◽  
Laura De Wilde ◽  
Kashika Singh ◽  
Patrick Tonnard ◽  
Alexis Verpaele ◽  
...  

Abstract Background Recent evidence confirms that mesenchymal stem cells (MSCs) facilitate angiogenesis mainly through paracrine function. Extracellular vesicles (EVs) are regarded as key components of the cell secretome, possessing functional properties of their source cells. Subsequently, MSC-EVs have emerged as a novel cell-free approach to improve fat graft retention rate. Objectives To provide a systematic review of all studies reporting the use of MSC-EVs to improve graft retention rate. Methods A systematic search was undertaken using the Embase, PubMed and the Cochrane Central Register of Controlled Trials databases. Outcome measures included donor/receptor organism of the fat graft, study model, intervention groups, evaluation intervals, EV research data, in vitro and in vivo results. Results Of the total 1717 articles, 62 full-texts were screened. Seven studies reporting on 294mice were included. Overall, EV treated groups showed higher graft retention rates compared to untreated groups. Notably, retention rate was similar following EV- and MSC-treatment. In addition to reduced inflammation, graft enrichment with EVs resulted in early revascularization and better graft integrity. Interestingly, hypoxic preconditioning of MSCs improved their beneficial paracrine effects and led to a more proangiogenic EV population, as observed by both in vitro and in vivo results. Conclusions MSC-EVs appear to offer an interesting cell-free alternative to improve fat graft survival. While their clinical relevance remains to be determined, it is clear that not the cells, but their secretome is essential for graft survival. Thus, a paradigm shift from cell-assisted lipotransfer towards ‘secretome-assisted lipotransfer’ is well on its way.

2021 ◽  
Vol 1 (1) ◽  
pp. 84-95
Author(s):  
Patience O. Obi ◽  
Jennifer E. Kent ◽  
Maya M. Jeyaraman ◽  
Nicole Askin ◽  
Taiana M. Pierdoná ◽  
...  

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.


2021 ◽  
Author(s):  
Jia-Ming Sun ◽  
Chia-Kang Ho ◽  
Ya Gao ◽  
Chio-Hou Chong ◽  
Dan-Ning Zheng ◽  
...  

Abstract Background: Our previous study proved that Salvia miltiorrhiza could enhance fat graft survival by promoting adipogenesis. However, the effect of salvianolic acid B (Sal-B), the most abundant and bioactive water-soluble compound in Salvia miltiorrhiza, on fat graft survival has not yet been investigated.Objective: This study aims to investigate whether salvianolic acid B could improve fat graft survival and promote preadipocyte differentiation. The underlying mechanism has also been studied.Methods: In vivo, 0.2 ml of Coleman fat was transplanted into nude mice with salvianolic acid B. The grafts were evaluated by HE and IF at 2 and 4 weeks posttransplantation and by micro-CT at 4 weeks posttransplantation. In vitro, the adipogenesis and proliferative activities of salvianolic acid B were analyzed in cultured human adipose-derived stem cells (h-ADSCs) and 3T3-L1 cells to detect the mechanism by which salvianolic acid B affects graft survival.Results: In vivo, the weights and volumes of the fat grafts in the Sal-B-treated groups were significantly higher than those of the fat grafts in the control group. In addition, higher fat integrity and more viable adipocytes were observed in the Sal-B-treated groups. In vitro, salvianolic acid B showed the ability to promote 3T3-L1 and h-ADSC proliferation and adipogenesis.Conclusions: Our in vitro experiments demonstrated that salvianolic acid B can promote the proliferation of adipose stem cells and enhance the differentiation of adipose stem cells. Simultaneously, in vivo experiments showed that salvianolic acid B can improve the survival rate of fat transplantation. Therefore, our research shed light on the potential therapeutic usage of salvianolic acid B in improving the survival rate of fat transplantation.


2021 ◽  
Author(s):  
Antoine AbdelMassih ◽  
Rafeef Hozaien ◽  
Meryam El Shershaby ◽  
Aya Kamel ◽  
Habiba-Allah Ismail ◽  
...  

Abstract Background: Postexposure prophylaxis has been an overlooked strategy in the context of COVID-19. Inhaled Nitric Oxide offers itself as a potential tool in this context. The aim of this systematic review was to depict previous in vivo and in vitro studies demonstrating an antiviral role for NO Methodology:Embase, Medline and the Cochrane Central Register were used to search for specific keywords such as “Nitric oxide” AND “Antiviral activity” for relevant publications up to 1st of June 2021. The systematic review was performed using PRISMA protocolResults:Twenty-one studies were identified depicting an antiviral role for Nitric Oxide. Those studies involved sixteen viruses. Only four of the depicted studies were clinical trials, while three were performed on a murine model. The remainder of the studies involved in vitro experimentation of the role of NO in halting viral replication of several viruses including SARS-CoV-2Conclusion: While early reports of NO role in the treatment of COVID-19 suggested its use for the treatment of established ARDS, NO seems to have a much earlier and more efficient prophylactic role. It inhibits a protease needed for canonical viral replication of SARS-CoV-2, namely Furin, by decreasing calcium's cytosolic levels. This might add a significant tool for postexposure chemoprophylaxis in the at-risk group, especially medical personnel.


2021 ◽  
Vol 30 ◽  
pp. 096368972110529
Author(s):  
Yi Yi ◽  
Weijie Hu ◽  
Wenchang Lv ◽  
Chongru Zhao ◽  
Mingchen Xiong ◽  
...  

Autologous fat grafting (AFG) is widely regarded as an important method for breast reconstruction after mastectomy among breast cancer (BC) patients. FTY720 has been proved to affect macrophage polarization and improve the sensitivity of postoperative BC treatment. This study aimed to explore FTY720 function and underlying mechanism in fat transplantation. The C57BL/6 J mice that received AFG were randomly divided into two groups treated with saline and FTY720, respectively. The fat graft samples were obtained at week 1, 2, 4, and 12 post-transplantation. Graft volumes, graft structures, M2 macrophages, and STAT3 protein expression were estimated by histological examination, immunofluorescence, flow cytometry, and western blot, respectively. In vitro, mouse preadipocytes were stimulated with FTY720 treated-M2 macrophages conditioned medium (FTY720-M2-CM) to evaluate the adipogenesis effect. The level of adipogenic mRNA expression in preadipocytes was detected by RT-PCR. The in vivo results showed that FTY720 treatment significantly enhanced the fat graft retention, structure integrity, and neovascularization, indicating the potential of FTY720 in improving graft survival. The histology results showed more polarized M2 macrophage presented in the FTY720 group. In the in vitro assay, after FTY720-M2-CM treatment, the 3T3-L1 preadipocytes showed the increased triglyceride content and adipogenic mRNA expression, including FABP4, C/EBP-α, Adipoq, and PPARγ. Furthermore, FTY720 treatment up-regulated the expression level of M2 biomarker CD206, Arg-1, Fizz-1, which could be weakened by the STAT3 inhibitor. Together, this study confirmed the potential efficacy of FTY720 in improving graft survival in the AFG model, possibly mediated by polarizing macrophages to M2 type through activating the STAT3 pathway.


Author(s):  
Hui-Yi Hsiao ◽  
Chao-Yi Lai ◽  
Jia-Wei Liu ◽  
Yuan-Yuan Yu ◽  
Frank Chun-Shin Chang ◽  
...  

Abstract Background Recently, there has been increasing research interest in identifying the effect of liposuction procedures on fat graft survival. Whether different harvest techniques affect the quality of fat grafts is unclear. In this study, fat grafts harvested using traditional suction-assisted liposuction (TSAL) and vibration amplification of sound energy at resonance (VASER) approaches were examined to assess the quality and survival of the grafts. Furthermore, the proliferation and differentiation potentials of adipose stem cells (ASCs) isolated from both liposuction approaches were investigated. Objectives Investigation of the effect of different liposuction approaches on the survival and regeneration potential of grafted fat tissue. Methods Fat grafts were collected from patients who underwent liposuction procedures with two different liposuction approaches. Some lipoaspirates were implanted into the subcutaneous layer of nu mice for 4 and 12 weeks. The other portion of the lipoaspirate was obtained for ASC isolation and subjected to proliferation and differentiation assays. Results Our results indicated that although in vivo fat grafting presented similar adipose tissue survival for the two different liposuction approaches, more angiogenesis and less fibrosis was observed in the group with VASER based on histological evaluation. Furthermore, VASER-derived ASCs presented better quality in terms of cell differentiation capacity. Conclusions In summary, our in vivo study confirmed better graft angiogenesis with less inflammation, apoptosis, and scar formation in the VASER group. ASCs harvested with VASER exhibited increased differentiation capacity, representing a great source for fat grafting and regenerative medicine.


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