Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts

Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

doi:10.1038/srep32993

Cited by 503 publications

(538 citation statements)

References 48 publications

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“…[7] Although the mechanism of the exosomes' role on proliferation and migration of fibroblasts was demonstrated, [8] no study has been conducted to identify the expressional changes of microRNAs, which play major role in various cellular responses, including proliferation.…”

Section: Introductionmentioning

confidence: 99%

“…[5] A study of stem cell transplantation therapy demonstrated that the role of MSCs in cell-tocell communication was exerted through a paracrine mechanism and that exosomes play a major role in this process. [6] Other findings also described that the conditioned media of ASC (ASC-CM) [7] or exosomes [8] were able to promote the migration of dermal fibroblasts during the process of wound healing. [7] Although the mechanism of the exosomes' role on proliferation and migration of fibroblasts was demonstrated, [8] no study has been conducted to identify the expressional changes of microRNAs, which play major role in various cellular responses, including proliferation.…”

Section: Introductionmentioning

confidence: 99%

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Exosomes from human adipose‐derived stem cells promote proliferation and migration of skin fibroblasts

Choi¹,

Seo²,

Woo³

et al. 2017

Experimental Dermatology

105

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This study was undertaken to evaluate whether exosomes from human adipose-derived stem cells (ASC-exo) can stimulate the regeneration of human dermal fibroblasts (HDFs). Immunoblotting and FACS analyses showed that ASC-exo was positive for exosome markers. Fluorescence tracking revealed that the contents of ASCexo were transferred into the HDFs. ASC-exo treatment also stimulated the proliferation and migration of HDFs in a dose-dependent manner. Similarly, the expression levels of genes involved in skin cell proliferation were increased by ASC-exo. Microarray analysis showed an enrichment of microRNAs that have regenerative function. We suggest that the ASC-exo can stimulate skin cell proliferation. | BACKGROUNDIt has been well reported that adipose tissue-derived stem cell (ASC) secretes various soluble factors, that is growth factors, cytokines, exosomes that can rescue damaged cells.[1] Exosome, a 30-to 150-nm-sized extracellular vesicle that is secreted from most cell types, is formed within endosomal compartments and released into the extracellular milieu.[2] It has been demonstrated that exosomes possess similar functional properties of mesenchymal stem cells (MSCs) from which they are derived, [3] and due to such functions, exosomes are regarded now as a communicator between tissues.[4] Functionally, exosomes can reduce the immune recognition, so that the integrity of cell membrane can be maintained. [5] A study of stem cell transplantation therapy demonstrated that the role of MSCs in cell-tocell communication was exerted through a paracrine mechanism and that exosomes play a major role in this process.[6] Other findings also described that the conditioned media of ASC (ASC-CM) [7] or exosomes [8] were able to promote the migration of dermal fibroblasts during the process of wound healing. [7] Although the mechanism of the exosomes' role on proliferation and migration of fibroblasts was demonstrated, [8] no study has been conducted to identify the expressional changes of microRNAs, which play major role in various cellular responses, including proliferation. | QUESTIONS ADDRESSEDWe asked whether ASC-derived exosomes can stimulate the skin dermal fibroblasts' proliferation and migration, and by what mechanism these exosomes play such functions. | EXPERIMENTAL DESIGNSee supplementary information. | RESULTSTransmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) showed that ASC-exo isolated from the supernatants (Fig. S1A). Western blot analysis revealed that ASC-exo expresses exosome markers HSP70, CD63and CD9 (Fig. S1B), while these markers were absent in ASC lysate.Flow cytometry analysis also showed that ASC-exos were positive for CD9, CD63 and CD81 (Fig. S1C). We next asked whether the contents of ASC-exos could be transmitted to HDFs. After co-incubation, for 24 hours, of PKH26-labelled ASC-exos with HDFs, it was found that red fluorescence of PKH26 was localized within the cytoplasm of HDFs (Fig. S1D), showing that ASC-exo can be internalized intoHDFs. Also, quantitati...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exosomes from human adipose‐derived stem cells promote proliferation and migration of skin fibroblasts

Choi¹,

Seo²,

Woo³

et al. 2017

Experimental Dermatology

105

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“…Therefore, more research should focus on ways to prevent and treat skin diseases. Various studies have identified an association between exosomes and skin diseases (23)(24)(25). For instance, melanoma cells secrete exosomes, which are abundant in the tumor microenvironment, to impact on the pathological process (26).…”

Section: Skinmentioning

confidence: 99%

“…In addition, adipose MSC-derived exosomes (ASCs-Exos) are internalized by fibroblasts to influence cell migration, proliferation and collagen synthesis (24). Histological analyses have indicated that the effect of ASCs-Exos on collagen is different between the early and later stages of wound healing, with increased collagen I and III synthesis at early stages and decreased collagen synthesis at later stages (24).…”

Section: Exosomes and Skin Wound Healingmentioning

confidence: 99%

Exosomes as a novel pathway for regulating development and diseases of the skin (Review)

Liu

Wang

2018

biom rep

Self Cite

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Abstract. Exosomes are one of the most potent intercellular communicators, which are able to communicate with adjacent or distant cells. Exosomes deliver various bioactive molecules, including membrane receptors, proteins, mRNA and microRNA, to target cells and serve roles. Recent studies have demonstrated that exosomes may regulate the functions and diseases of the skin, which is the largest organ of the human body. The abnormal functions of the skin lead to the progression of scleroderma, melanoma, baldness and other diseases. A previous study has demonstrated that epithelial progenitor cells are rich in several subunits of exosomes that may maintain the proliferative capacity of these epithelial progenitor cells, which is essential for the development of the epidermis. Exosomes derived from human adipose mesenchymal stem cells accelerate skin wound healing by optimizing fibroblast properties; this is beneficial for the recovery of postoperative and other wounds. Exosomes derived from adipocytes promote melanoma migration and invasion through fatty acid oxidation; therefore, in the clinic, it may be possible to improve the prognosis of patients with melanoma by reducing their body fat content. Exosomes derived from keratinocytes modulate melanocyte pigmentation, which has been utilized as a novel mechanism for the regulation of pigmentation in conditions including Moynahan syndrome and albinism. Meanwhile, scleroderma patients with vascular abnormalities may experience decreased serum exosome levels; it may therefore be possible to detect the exosome content in sera in order to diagnose and treat scleroderma. In addition, the use of exosomes has been suggested to promote or enhance hair growth, which has been demonstrated to be highly effective. These studies have provided new opportunities and therapeutic strategies for understanding how exosomes regulate intercellular communication in pathological processes of the skin.

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“…Human ASCs were obtained and treated with an exosome precipitation solution [23]. Full-thickness wounds were created on the backs of Balb/c mice and four groups treatment groups administered: 1) no treatment control, 2) saline injected control, 3) exosome in saline subcutaneous injection, and 4) exosome in saline intravenously injected.…”

Section: Adipose-derived Mscsmentioning

confidence: 99%

Mesenchymal Stem Cell Therapies for Skin Repair and Regeneration

2017

JDC

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In the clinic, partial to full-thickness skin defects are generally treated through debridement and patching with autologous skin grafts. Autologous skin grafts are in severely limited supply, especially for ill patients lacking healthy tissue to donate to themselves. Stem cells have come into interest as a novel, viable way to heal skin wounds. Mesenchymal stem cells (MSCs) are of particular interest due to its common mesoderm germ layer origins as skin tissue. Mesenchymal stem cells are primarily derived from bone marrow, adipose tissue and umbilical cord. Bone marrow MSCs have been widely applied to chronic wounds in non-diabetic and diabetic subjects with positive results for wound healing and closure. Adipose-derived stem cells (ASCs) are a more recent application to skin healing. It has been found that ASCs secrete growth factors positive for augmenting wound healing, such as TGF-β. ASCs are also a more attractive cell source for clinical use due their great abundance and ease of procurement from discarded tissues from cosmetic surgery procedures. Most recently, umbilical cord MSCs have been tested for its effects on wound healing, showing that the cells' paracrine effects can accelerate skin wound healing. Overall, mesenchymal stem cells show great promise to progress skin wound treatments, especially for chronic wounds. However, more clinical research is needed prior to patient application. Mesenchymal Stem Cell Therapies for Skin Repair and Regeneration 2/3Copyright: ©2017 Lam in group 1 and 76% of patients in group 2 did not need further wound care. In contrast, 80% of patients in the saline control group required surgical intervention. In a 16 month follow-up with group 2, the wound was completely healed with no signs of contracture.Chronic wounds are a notorious complication for diabetic patients. Bone marrow MSCs have been explored as a treatment option [15][16][17]. In one study, allogeneic MSCs were compared to the MSCs' acellular derivatives in a non-obese diabetic (NOD) mouse model [15]. The cells or acellular derivatives were intradermally injected around the wound site. Mice treated with the acellular derivative displayed significantly higher percentages of wound closure on days 4, 6, and 8 compared to wounds that received cells or control vehicles. Acellular products produced less pronounced inflammatory response, more granulation tissue, and a higher density of collagen fibers. This study suggests that growth factors present in bone marrow MSCs require time for cell release, whereas during the decellularization process these growth factors are released and readily available to stimulate the wound healing process. Adipose-derived MSCsWhile bone marrow MSCs can be difficult to obtain, adiposederived stem cells (ASCs) are much more abundant and are easily isolated from subcutaneous fat tissue and lipoaspirates. In addition, these adipose tissues are generally discarded from plastic surgery clinics, making excellent use of otherwise disposed tissue. ASCs have been widely explored for sk...

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Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts

Cited by 503 publications

References 48 publications

Exosomes from human adipose‐derived stem cells promote proliferation and migration of skin fibroblasts

Exosomes from human adipose‐derived stem cells promote proliferation and migration of skin fibroblasts

Exosomes as a novel pathway for regulating development and diseases of the skin (Review)

Mesenchymal Stem Cell Therapies for Skin Repair and Regeneration

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