Mesenchymal stem cells-derived MFG-E8 accelerates diabetic cutaneous wound healing

Uchiyama, Akihiko; Motegi, Sei‐ichiro; Sekiguchi, Akiko; Fujiwara, Chisako; Perera, Buddhini; Ogino, Sachiko; Yokoyama, Yoko; Ishikawa, Osamu

doi:10.1016/j.jdermsci.2017.02.285

Cited by 42 publications

(45 citation statements)

References 50 publications

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“…Increasing evidence points to the essential function of MFG‐E8 in diverse physiological functions such as inflammation and apoptosis . Macrophages participate in tissue regeneration by regulating inflammation and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Animals were randomly divided into three groups ( n = 24/group): control group, window defect injury without any treatment; fibrin group, window defect was filled with 10 μl of fibrin sealant alone; and rMFG‐E8, 10 μl of fibrin sealant containing 400 ng rMFG‐E8 (R&D Systems, Minneapolis, MN) was inoculated into the tendon window defect. The dosage of rMFG‐E8 was based on other study of this kind in the literatures . The fibrin sealant (Baxter®, Vienna, Austria) used in many kinds of research act as a useful vehicle of growth factors.…”

Section: Methodsmentioning

confidence: 99%

“…In addition to its role in regulating apoptosis and inflammation, MGF‐E8 also possesses effect in modulating angiogenesis. It is currently an attractive solution for cutaneous wound healing, as it was shown to modulate the inflammatory environment and recover organ dysfunction . In addition, MFG‐E8 can prevent tissue damage by executing a pivotal role in the scavenging of apoptotic cells from affected tissues …”

Section: Introductionmentioning

confidence: 99%

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MFG‐E8 regulates inflammation and apoptosis in tendon healing, and promotes tendon repair: A histological and biochemical evaluation

et al. 2019

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Several studies have identified potential roles for MFG-E8 in promoting tissue repair. However, the effects of MFG-E8 on tendon repair have not yet been investigated.Therefore, we explored the role of MFG-E8 on tendon repair using a rat model of patellar tendon injury. The patellar tendons of Sprague Dawley rats (n = 24/group) received window defects and, after modeling, three groups were randomly assigned: (a) recombinant MFG-E8 (rMFG-E8) group, implantation with MFG-E8 and fibrin glue (400 ng in 10 μl); (b) fibrin group, implantation with fibrin only; and (c) control group, without any treatment. Histopathology, immunohistochemistry, and gene expression analyses were performed at 2 and 4 weeks after healing. Administration of rMFG-E8 in injury sites significantly improved tendon healing histologically at 4 weeks after injury. In addition, numbers of M1 macrophages and M1-stimulator genes, including IFNG, Il-1B, and Il-6, were reduced in the repair sites at 2 weeks by rMFG-E8 administration. In parallel, rMFG-E8 significantly increased the number of M2 macrophages and expression of anti-inflammatory IL-10 and IL-4 at 2 weeks after injury. Treatment with rMFG-E8 markedly decreased tendon cell apoptosis. Moreover, rMFG-E8 significantly enhanced the expression of genes related to tendon matrix formation at 2 weeks after injury, including Col1a1and tenascin-C. We conclude that MFG-E8 could regulate inflammatory responses and apoptotic cell accumulation in tendon repair, and promote the healing process of injured tendon tissue. Thus, exogenous application of MFG-E8 might have therapeutic potential for repair of tendon injuries. K E Y W O R D S apoptosis, healing, inflammation, MFG-E8, tendon

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MFG‐E8 regulates inflammation and apoptosis in tendon healing, and promotes tendon repair: A histological and biochemical evaluation

et al. 2019

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“…Mesenchymal stem cells (MSCs), which are known to contribute to tissue regeneration and repair [1] are normally present in a dormant state in almost all organs [2]. Upon the release of cytokines by a stimulus such as inflammation or tissue injury, MSCs begin to proliferate and migrate to where cytokines are being released [3].…”

Section: Introductionmentioning

confidence: 99%

Novel Application Method for Mesenchymal Stem Cell Therapy Utilizing Its Attractant-Responsive Accumulation Property

et al. 2019

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Stem cell therapy is an emerging treatment modality for various diseases. Because mesenchymal stem cells (MSCs) are known to accumulate at the site of damage, their possible clinical application has been investigated. MSCs are usually administered using intravenous injection, but this route carries a risk of pulmonary embolism. In contrast, topical injection of MSCs reportedly has an inferior therapeutic effect. We developed a remote administration method that uses collagen gel as a scaffold and investigated the effect of this scaffold on the retention of stemness, homing ability, and therapeutic effect using a mouse tooth extraction model. After verifying the retention of stemness of MSCs isolated from the bone marrow of donor mice in the scaffold, we administered MSCs subcutaneously into the back of the recipient mice with scaffold and observed the accumulation and the acceleration of healing of the extraction socket of the maxillary first molar. The MSCs cultured with scaffold retained stemness, the MSCs injected into back skin with scaffold successfully accumulated around the extraction socket, and socket healing was significantly enhanced. In conclusion, administration of MSCs with collagen scaffold at a remote site enhanced the lesion healing without the drawbacks of currently used administration methods.

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“…Mesenchymal stem cells (MSCs), which are known to contribute to tissue regeneration and repair [1], are normally present in a dormant state in almost all organs [2]. Upon the release of cytokines by a stimulus such as inflammation or tissue injury, MSCs begin to proliferate and migrate to the site from where cytokines are being released; i.e.…”

Section: Introductionmentioning

confidence: 99%

Novel application method for mesenchymal stem cell therapy utilizing its attractant–responsive accumulation property

Ueda

Atsuta

Ayukawa

et al. 2019

Preprint

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Objectives: It remains difficult to control the delivery of appropriate amounts of mesenchymal stem cell (MSC)-based cell therapies. To examine the ability of MSCs to accumulate at sites of damage and potential therapeutic benefit of providing continuous migration of MSCs to these sites, we observed the effect of MSCs administered in a collagen gel scaffold on healing of a tooth extraction site. Materials and Methods:MSCs isolated from the bone marrow of green fluorescent protein (GFP)-expressing donor mice were expanded for 3 weeks in three-dimensional (3-D) culture using a collagen gel scaffold, and evaluated to confirm the efficacy of the scaffold. Next, MSCs suspended in collagen gel were subcutaneously administered into the backs of mice. Two days later, extraction of the maxillary first molar was carried out. Numbers of MSCs in scaffolds, migration and accumulation around the extracted tooth cavity, extraction site healing, and presence of MSCs in vital organs were evaluated.Results: MSCs cultured in the collagen gel scaffold maintained stemness for 2 weeks.After subcutaneous administration, numbers of MSCs in scaffolds slightly decreased over time, but cells survived for at least 2 weeks. After tooth extraction, GFP-expressing MSCs were confirmed in the surrounding mucosa of the extracted tooth cavity; in the scaffold group, numbers of MSCs increased over time and fewer were observed in lung tissue. Wound healing was enhanced by injection of MSCs via the tail vein or into the back compared with the untreated control group.Conclusions: Delivery in a collagen gel could maintain the characteristics of MSCs, which migrated to the damaged area and promoted wound healing without side effects occurring with conventional administration methods.

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Mesenchymal stem cells-derived MFG-E8 accelerates diabetic cutaneous wound healing

Abstract: MSCs-derived MFG-E8 might accelerate diabetic wound healing by promoting angiogenesis, the clearance of apoptotic cells, and the infiltration of M2 macrophages, and by suppressing inflammatory cytokines in wound area.

Cited by 42 publications

References 50 publications

MFG‐E8 regulates inflammation and apoptosis in tendon healing, and promotes tendon repair: A histological and biochemical evaluation

MFG‐E8 regulates inflammation and apoptosis in tendon healing, and promotes tendon repair: A histological and biochemical evaluation

Novel Application Method for Mesenchymal Stem Cell Therapy Utilizing Its Attractant-Responsive Accumulation Property

Novel application method for mesenchymal stem cell therapy utilizing its attractant–responsive accumulation property

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