Hypoxia adipose stem cell-derived exosomes promote high-quality healing of diabetic wound involves activation of PI3K/Akt pathways

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Abstract

Refractory diabetic wounds can cause persistent inflammation and delayed healing due to hypoxia. Currently, no optimal solution is available. Exosomes of adipose stem cells (ADSCs-exo) may promote skin wound healing, however, molecular mechanisms remains mysterious. We found significantly enhanced survival and proliferation of adipose stem cells after hypoxia induction compared to normoxia. Here, we aimed to investigate if hypoxic adipose stem cells exosomes (HypADSCs-exo) participate in hypoxia adaptability and accelerate diabetic wound healing. Based on high-throughput sequencing, 215 microRNAs (miRNAs) were upregulated and 369 miRNAs downregulated in HypADSCs-exo compared to ADSCs-exo. Up-regulated miR-21-3p, miR-126-5p, miR-31-5p whereas down-regulated gene miR-99b and miR-146-a correlated with wound healing. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), miRNAs might regulate cell metabolism, differentiation and Transforming growth factor-β (TGF-β) function. Consistently, HpyADSCs-exo could promote diabetic wounds healing and inhibit inflammation through PI3K/AKT signaling pathway. Collectively, HpyADSCs-exo can promote diabetic wound healing as an alternative strategy to improve wound healing.

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The online version contains supplementary material available at 10.1186/s12951-021-00942-0.

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Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles.

Marina Colombo, Graça Raposo, Clotilde Théry (2014)

In the 1980s, exosomes were described as vesicles of endosomal origin secreted from reticulocytes. Interest increased around these extracellular vesicles, as they appeared to participate in several cellular processes. Exosomes bear proteins, lipids, and RNAs, mediating intercellular communication between different cell types in the body, and thus affecting normal and pathological conditions. Only recently, scientists acknowledged the difficulty of separating exosomes from other types of extracellular vesicles, which precludes a clear attribution of a particular function to the different types of secreted vesicles. To shed light into this complex but expanding field of science, this review focuses on the definition of exosomes and other secreted extracellular vesicles. Their biogenesis, their secretion, and their subsequent fate are discussed, as their functions rely on these important processes.

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Type 2 diabetes.

Melanie Davies, Sudesna Chatterjee, Kamlesh Khunti (2017)

415 million people live with diabetes worldwide, and an estimated 193 million people have undiagnosed diabetes. Type 2 diabetes accounts for more than 90% of patients with diabetes and leads to microvascular and macrovascular complications that cause profound psychological and physical distress to both patients and carers and put a huge burden on health-care systems. Despite increasing knowledge regarding risk factors for type 2 diabetes and evidence for successful prevention programmes, the incidence and prevalence of the disease continues to rise globally. Early detection through screening programmes and the availability of safe and effective therapies reduces morbidity and mortality by preventing or delaying complications. Increased understanding of specific diabetes phenotypes and genotypes might result in more specific and tailored management of patients with type 2 diabetes, as has been shown in patients with maturity onset diabetes of the young. In this Seminar, we describe recent developments in the diagnosis and management of type 2 diabetes, existing controversies, and future directions of care.

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Concise Review: MSC-Derived Exosomes for Cell-Free Therapy.

Donald Phinney, Mark F. Pittenger (2017)

Mesenchymal stem cell transplantation is undergoing extensive evaluation as a cellular therapy in human clinical trials. Because MSCs are easily isolated and amenable to culture expansion in vitro there is a natural desire to test MSCs in many diverse clinical indications. This is exemplified by the rapidly expanding literature base that includes many in vivo animal models. More recently, MSC-derived extracellular vesicles (EVs), which include exosomes and microvesicles (MV), are being examined for their role in MSC-based cellular therapy. These vesicles are involved in cell-to-cell communication, cell signaling, and altering cell or tissue metabolism at short or long distances in the body. The exosomes and MVs can influence tissue responses to injury, infection, and disease. MSC-derived exosomes have a content that includes cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. To the extent that MSC exosomes can be used for cell-free regenerative medicine, much will depend on the quality, reproducibility, and potency of their production, in the same manner that these parameters dictate the development of cell-based MSC therapies. However, the MSC exosome's contents are not static, but rather a product of the MSC tissue origin, its activities and the immediate intercellular neighbors of the MSCs. As such, the exosome content produced by MSCs appears to be altered when MSCs are cultured with tumor cells or in the in vivo tumor microenvironment. Therefore, careful attention to detail in producing MSC exosomes may provide a new therapeutic paradigm for cell-free MSC-based therapies with decreased risk. Stem Cells 2017;35:851-858.

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Author and article information

Contributors

Zhibo Xiao: xiaozhibodoctor@126.com

Journal

Journal ID (nlm-ta): J Nanobiotechnology

Journal ID (iso-abbrev): J Nanobiotechnology

Title: Journal of Nanobiotechnology

Publisher: BioMed Central (London )

ISSN (Electronic): 1477-3155

Publication date (Electronic): 7 July 2021

Publication date PMC-release: 7 July 2021

Publication date Collection: 2021

Volume: 19

Electronic Location Identifier: 202

Affiliations

GRID grid.412463.6, ISNI 0000 0004 1762 6325, Department of Plastic and Aesthetic Surgery, , The Second Affiliated Hospital of Harbin Medical University, ; Harbin, 150081 People’s Republic of China

Article

Publisher ID: 942

DOI: 10.1186/s12951-021-00942-0

PMC ID: 8261989

PubMed ID: 34233694

SO-VID: 8f0892d2-91a6-470c-99e0-416581d5d285

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 17 May 2021

Date accepted : 23 June 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81471796

Award Recipient : Zhibo Xiao

Funded by: FundRef http://dx.doi.org/10.13039/501100009993, Excellent Youth Foundation of Heilongjiang Province of China;

Award ID: JC2017019

Award Recipient : Zhibo Xiao

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ScienceOpen disciplines: Biotechnology

Keywords: diabetic wound,hypoxia,exosomes,adscs,pi3k/akt

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ScienceOpen disciplines: Biotechnology

Keywords: diabetic wound, hypoxia, exosomes, adscs, pi3k/akt

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Hypoxia adipose stem cell-derived exosomes promote high-quality healing of diabetic wound involves activation of PI3K/Akt pathways

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Most cited references 50

Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles.

Type 2 diabetes.

Concise Review: MSC-Derived Exosomes for Cell-Free Therapy.

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