Mesenchymal stem cells ameliorate impaired wound healing through enhancing keratinocyte functions in diabetic foot ulcerations on the plantar skin of rats

Katō, Jirō; Kawanishi, Hideki; Himeno, Tatsuhito; Shibata, Tsutomu; Kondo, Masaki; Okawa, Tetsuji; Fujiya, Atsushi; Fukami, Ayako; Uenishi, Eita; Seino, Yusuke; Tsunekawa, Shin; Hamada, Yoji; Naruse, Keiko; Oiso, Yutaka; Nakamura, Jiro

doi:10.1016/j.jdiacomp.2014.05.003

Cited by 64 publications

(41 citation statements)

References 23 publications

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“…Allogeneic BM-MSCs shortened the duration of wound healing in diabetic foot ulcerations on the plantar skin of rats via the improvement of keratinocytes which had been mentioned in vitro [33]. It has been found that BM-MSCs isolated from rats not only promote human keratinocytes (HKCs) to produce cytokine including matrix metalloproteinase-2 (MMP-2), epidermal growth factor (EGF), and insulin-like growth factor 1 (IGF-1) [33], but also enhance the migration and proliferation of rat keratinocytes by upregulating MMP-2 and matrix metalloproteinase-9 (MMP-9) and downregulating tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2), as well as triggering Erk signaling pathway [58] (Figure 1). …”

Section: Bm-mscs and Dfumentioning

confidence: 99%

“…Nowadays, a growing number of diseases can be improved via wide applications of stem cell transplantation, such as congenital cataract [12], diabetic retinopathy and keratopathy [13], myocardial infarction [14], ocular surface burns [15, 16], serious skin burns [17, 18], Parkinson's disease [19], Huntington's disease [20], and especially DFU [21]. Accumulating evidence has pointed out that mesenchymal stem cells (MSCs) may enhance wound healing [22–24] and be served as a cell source for many tissue engineering applications including bone regeneration [25], cartilage regeneration [26–28], myocardial regeneration [29], neurogenesis [30, 31], inflammatory bowel diseases [32], and DFU [33, 34]. MSCs exist in many tissues, for example, bone marrow [35, 36], umbilical cord [37, 38], placenta [39, 40], adipose tissue [36, 41–43], gingiva [44, 45], oral mucosa [46], amniotic fluid [47], and brain [48].…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

Cao

Gang

Wang

2017

Journal of Diabetes Research

127

108

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Mesenchymal stem cells (MSCs), an ideal cell source for regenerative therapy with no ethical issues, play an important role in diabetic foot ulcer (DFU). Growing evidence has demonstrated that MSCs transplantation can accelerate wound closure, ameliorate clinical parameters, and avoid amputation. In this review, we clarify the mechanism of preclinical studies, as well as safety and efficacy of clinical trials in the treatment of DFU. Bone marrow-derived mesenchymal stem cells (BM-MSCs), compared with MSCs derived from other tissues, may be a suitable cell type that can provide easy, effective, and cost-efficient transplantation to treat DFU and protect patients from amputation.

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Section: Bm-mscs and Dfumentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

Cao

Gang

Wang

2017

Journal of Diabetes Research

127

108

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“…In particular, IGF-1 is strongly expressed in the injury area, where it plays an important role in both epidermal and dermal wound-healing [126]. Recently, BM-MSCs were used in a rodent model of diabetic foot ulceration and were demonstrated to improve wound-healing and to increase the expression of local GFs including IGF-1, EGF, and MMP2 [127]. …”

Section: The Role Of Igfs In Mesenchymal Stem Cell Fate Specificatmentioning

confidence: 99%

The Roles of Insulin-Like Growth Factors in Mesenchymal Stem Cell Niche

Youssef

Aboalola

Han

2017

Stem Cells International

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Many tissues contain adult mesenchymal stem cells (MSCs), which may be used in tissue regeneration therapies. However, the MSC availability in most tissues is limited which demands expansion in vitro following isolation. Like many developing cells, the state of MSCs is affected by the surrounding microenvironment, and mimicking this natural microenvironment that supports multipotent or differentiated state in vivo is essential to understand for the successful use of MSC in regenerative therapies. Many researchers are, therefore, optimizing cell culture conditions in vitro by altering growth factors, extracellular matrices, chemicals, oxygen tension, and surrounding pH to enhance stem cells self-renewal or differentiation. Insulin-like growth factors (IGFs) system has been demonstrated to play an important role in stem cell biology to either promote proliferation and self-renewal or enhance differentiation onset and outcome, depending on the cell culture conditions. In this review, we will describe the importance of IGFs, IGF-1 and IGF-2, in development and in the MSC niche and how they affect the pluripotency or differentiation towards multiple lineages of the three germ layers.

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“…At present, the paracrine signaling theory is preferred as a plausible explanation for the therapeutic effects of these cells. 26,27 The paracrine factors secreted by MSCs can accumulate in the conditioned medium (CM), which has been reported to serve multiple positive functions in tissue regeneration. 28,29 Studies have shown that MSC-CM plays an anti-inflammatory role in corneal wound healing following chemical injury.…”

mentioning

confidence: 99%

Mesenchymal Stem Cell–Conditioned Medium Improves the Proliferation and Migration of Keratinocytes in a Diabetes-Like Microenvironment

Zhao

Hao

et al. 2015

The International Journal of Lower Extremity Wounds

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The impairment of wound healing in diabetic patients is an important clinical problem. Proper keratinocyte migration and proliferation are the crucial steps during reepithelialization, and these steps may be impaired in diabetes mellitus (DM) due to hyperglycemia and chronic inflammation in wound site. In this study, we explored the effects of diabetes-like microenvironment with high glucose (HG) and intense inflammation on the migration and proliferation of keratinocytes in vitro. We found that the migration and proliferation of rat keratinocytes were reduced with HG and lipopolysaccharide (LPS) stimulation via Erk signaling pathway in a reactive oxygen species (ROS)-dependent manner. Nevertheless, mesenchymal stem cell-conditioned medium (MSC-CM) counteracts the effects of HG and LPS. Treatment of rat keratinocyte with MSC-CM decreased HG- and/or LPS-induced ROS overproduction. Furthermore, MSC-CM reversed the downregulation of phosphorylation of MEK1/2 and Erk 1/2, which was induced by HG and/or LPS without affecting total levels. Our results may provide a possible mechanism for delayed wound healing in DM and provide a foundation to develop MSC-CM as an alternative therapeutic strategy to ameliorate the poor wound-healing conditions.

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Mesenchymal stem cells ameliorate impaired wound healing through enhancing keratinocyte functions in diabetic foot ulcerations on the plantar skin of rats

Cited by 64 publications

References 23 publications

Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

The Roles of Insulin-Like Growth Factors in Mesenchymal Stem Cell Niche

Mesenchymal Stem Cell–Conditioned Medium Improves the Proliferation and Migration of Keratinocytes in a Diabetes-Like Microenvironment

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