Human adipose tissue-derived stem cells inhibit the activity of keloid fibroblasts and fibrosis in a keloid model by paracrine signaling

Liu, Jian-Lan; Ren, Jie; Su, Linlin; Cheng, Shimeng; Zhou, Jing; Ye, Xiaolu; Yabin, Dong; Sun, Silei; Qi, Fazhi; Liu, Zhifei; Pleat, Jonathon; Zhai, Hongjun; Zhu, Nianyong

doi:10.1016/j.burns.2017.08.017

Cited by 50 publications

(62 citation statements)

References 47 publications

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“…The percentage induction of keloid tumors in the murine xenograft model of the present study is consistent with that of other workers [21,[41][42][43][44][45][46]. Our results showed that AKCs administered with hydroxyapatite (HA) produced 100% of keloid tumors in SCID mice and HNA staining confirmed that the tumors were indeed those of human origin.…”

Section: Discussionsupporting

confidence: 92%

Inhibition of growth of Asian keloid cells with human umbilical cord Wharton’s jelly stem cell-conditioned medium

Subramanian

Shen²,

Choolani

et al. 2020

Stem Cell Res Ther

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Background: Keloid formation occurs in Caucasian, African, and Asian populations and is a severe psychosocial burden on patients. There is no permanent treatment for this problem as its pathogenesis is not properly understood. Furthermore, differences in keloid behavior between ethnic groups are not known. It has been hypothesized that keloids behave like benign tumors because of their uncontrolled growth. The present study evaluated the tumoricidal properties of human Wharton's jelly stem cell-conditioned medium (hWJSC-CM) on fresh Asian keloid cells (AKCs). Methods: Human Wharton's jelly stem cells (hWJSCs) and AKCs were isolated based on our previous methods. hWJSCs and human skin fibroblasts (HSF) (controls) were used to collect hWJSC-CM and HSF-conditioned medium (HSF-CM). AKCs were treated with hWJSC-CM and HSF-CM in vitro and in vivo in a human keloid xenograft SCID mouse model. The inhibitory effect of hWJSC-CM on AKCs was tested in vitro using various assays and in vivo for attenuation/abrogation of AKC tumors created in a xenograft mouse model. Results: qRT-PCR analysis showed that the genes FN1, MMP1, and VCAN were significantly upregulated in AKCs and ANXA1, ASPN, IGFBP7, LGALS1, and PTN downregulated. AKCs exposed to hWJSC-CM in vitro showed significant decreases in cell viability and proliferation, increases in Annexin V-FITC+ cell numbers, interruptions of the cell cycle at Sub-G1 and G2/M phases, altered CD marker expression, downregulated anti-apoptotic-related genes, and upregulated pro-apoptotic and autophagy-related genes compared to controls. When AKCs were administered together with hWJSC-CM into immunodeficient mice there were no keloid tumors formed in 7 mice (n = 10) compared to the untreated control mice. When hWJSC-CM was injected directly into keloid tumors created in mice there were significant reductions in keloid tumor volumes and weights in 30 days.Conclusions: hWJSC-CM inhibited the growth of AKCs in vitro and in xenograft mice, and it may be a potential novel treatment for keloids in the human. The specific molecule(s) in hWJSC-CM that induce the anti-keloid effect need to be identified, characterized, and tested separately in larger preclinical and clinical studies.

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Section: Discussionsupporting

confidence: 92%

Inhibition of growth of Asian keloid cells with human umbilical cord Wharton’s jelly stem cell-conditioned medium

Subramanian

Shen²,

Choolani

et al. 2020

Stem Cell Res Ther

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“…These effects were associated with reduced accumulation of CD68 + and CD31+ cells and lower blood vessel densities and collagen deposition. 70 MSC-conditioned medium reduced the viability, α-SMA expression, and collagen secretion of keloid fibroblasts in vitro. Moreover, intralesional injections of the BM-MSC-conditioned medium (100 μL daily for 3 weeks) into a bleomycin-induced dermal fibrosis mouse model significantly decreased skin fibrosis.…”

Section: Stem Cell Therapiesmentioning

confidence: 90%

“…Furthermore, when injected into the keloid implantation athymic mouse model, ASCs‐CM induced the shrinkage of the keloid implant. These effects were associated with reduced accumulation of CD68 + and CD31+ cells and lower blood vessel densities and collagen deposition . MSC‐conditioned medium reduced the viability, α‐SMA expression, and collagen secretion of keloid fibroblasts in vitro.…”

Section: Stem Cell Therapiesmentioning

confidence: 94%

Managing keloid scars: From radiation therapy to actual and potential drug deliveries

Huang

Liu

You

et al. 2019

International Wound Journal

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The aetiology of keloids is becoming clearer, but many questions remain, including about the most optimal treatment. Current therapies include surgical excision, radiotherapy, and various pharmaceutical drugs. However, none of these drugs are keloid‐specific. Moreover, all current interventions are associated with high recurrence rates. Here, we review the pharmaceutical interventions that are currently available. All are based on the fact that keloids are an expanding solid mass with intense chronic inflammation at its advancing edges. Consequently, current pharmaceuticals aim to reduce the mass and/or symptoms of keloids, similar to surgery and radiotherapy. They include chemotherapies, immunotherapies, volume‐reducing therapies, and anti‐inflammatory therapies. We also describe new advances in keloid pharmaceuticals. They include drugs that were designed to treat systemic diseases such as hypertension or breast cancer but were found to also treat keloids. Furthermore, recent progress in genetic, epigenetic, and stem cell therapies suggests that they could become useful in the keloid field. This review of pharmaceutical advances will hopefully promote additional research and the development of effective and specific pharmaceuticals for keloids.

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“…(19) Evidence accumulated in recent years suggests that MSCs contribute to the healing of wounds without scars and prevent the formation of fibrous tissue, which makes them potentially effective for the formation of a normotrophic scars that are hardly noticeable, which is highly desirable in the head and neck. (20) However, the search for means to reduce the duration of inflammation revealed that human dermal fibroblasts are the source of adiponectin, which acts as an active anti-inflammatory cytokine and induces the production of anti-inflammatory factors, such as IL-10 and IL-1RA. (21) In addition, fibroblasts, unlike MSCs, are not oncogenic and have low expression of histocompatibility antigens, which allows the use of populations of both auto and xenofibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Prevention of the Formation of Unaesthetic Scars Following the Surgical Cutaneous Wounds Healing of the Jaw and Facial Region Based on Transplantation of Xenogenic Fibroblasts

Morozova¹,

Baranovsky²,

Shapovalova³

et al. 2019

IJBM

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The purpose of this study was to optimize healing and prevent the formation of unaesthetic scars of the maxillofacial region by transplanting xenogenic dermal fibroblasts (XDFs) into a fresh surgical wound. Materials and Methods: A total of 26 patients were selected with formations located on the skin of the face and neck, which could be compared with symmetrical areas of the healthy side. The patients were divided into 2 groups-the main group (Group 1) and the control group (Group 2). In Group 2 (n=12), a neoplasm was dissected, followed by grafting with local tissues, and in the Group 1 (n=14), a culture suspension of XDFs was injected by a tunnel method into the wound edges before stitching. The area of scar formation was determined using the LesionMeter program for the Android operating system. Contact thermography was carried out using thermo indicator films (CelluVision kit, IPS Italy). Results: The analysis of the parameters of the young scar formation on Day 30 after the operation makes it possible to state that the introduction of cell culture of XDFs in the wound edges has a positive effect on the healing rate of surgical wounds, decreases the inflammatory response and contributes to the development of a distinctively positive scar in terms of its quality and functional characteristics. By Day 30, the primary surgical wound area was reduced by 67.69%, and 71.43% of patients had soft and thin aesthetic scars with microcirculation that were not distinguishable from the surrounding skin and the skin of symmetrical areas of the face or neck. In patients of the control group, without fibroblast transplantation, the area decreased by only 50.0% and aesthetic scars were formed only in 41.67% of cases. In 16.67% of patients, the presence of wide, dense, cold (due to weak vascularization) hypotrophic scars was noted. Hyperthermia persists around these scars, indicating a weak inflammatory response Conclusion: The use of a cell culture suspension of XDFs in the treatment of postoperative surgical wounds opens up new real possibilities for reducing the incidence of inflammatory reactions, stimulates healing processes and contributes to the development of more functionally and aesthetically acceptable scars on the face and neck.

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Human adipose tissue-derived stem cells inhibit the activity of keloid fibroblasts and fibrosis in a keloid model by paracrine signaling

Cited by 50 publications

References 47 publications

Inhibition of growth of Asian keloid cells with human umbilical cord Wharton’s jelly stem cell-conditioned medium

Inhibition of growth of Asian keloid cells with human umbilical cord Wharton’s jelly stem cell-conditioned medium

Managing keloid scars: From radiation therapy to actual and potential drug deliveries

Prevention of the Formation of Unaesthetic Scars Following the Surgical Cutaneous Wounds Healing of the Jaw and Facial Region Based on Transplantation of Xenogenic Fibroblasts

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