Myeloid cell dysfunction and the pathogenesis of the diabetic chronic wound

Wicks, Kate; Torbica, Tanja; Mace, Kimberly A.

doi:10.1016/j.smim.2014.04.006

Cited by 79 publications

(73 citation statements)

References 132 publications

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“…Especially in diabetic patients have chronic nonhealing wounds been linked to disturbed angiogenesis and lymphangiogenesis [ 55 ] . Roughly 15-25 % of diabetics will develop a diabetic foot ulcer, which represents one of the most common complications, and accounts for more than 80 % of all lower leg amputations [ 56 ] .…”

Section: Angiogenesis and Vasculogenesis In Chronic Woundsmentioning

confidence: 99%

“…Eine Beeinträchtigung der Angiogenese und eine geringere Mobilisierung endothelialer Progenitorzellen aus dem Knochenmark sind weitere Faktoren, die zu Wundheilungsstörungen bei älteren Menschen beitragen[ 4 ] . Insbesondere bei Diabetespatienten wurden chronische, nicht heilende Wunden mit gestörter Angiogenese und Lymphangiogenese in Verbindung gebracht[ 55 ] . Etwa 15-25 % der Diabetiker entwickeln ein diabetisches Fußulkus, das eine der häufi gsten Komplikationen ist und für mehr als 80 % aller Unterschenkelamputationen verantwortlich ist[ 56 ] .…”

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Pathogenesis of wound healing disorders in the elderly

Makrantonaki

Wlaschek

Scharffetter‐Kochanek

2017

J Deutsche Derma Gesell

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Summary The elderly constitute the age group most susceptible to wound healing disorders and chronic wounds, the most prevalent being venous leg ulcers, pressure ulcers, and diabetic foot ulcers. However, other age‐associated diseases should also be taken into consideration in the diagnostic workup of chronic wounds, and not be underestimated. A better understanding of the pathomechanisms involved in the wound healing process is of key importance in combatting the difficulties associated with the treatment of chronic wounds. In recent decades, considerable progress has been made in the development of pioneering therapeutic strategies for chronic wounds. In this context, the use of growth factors and cytokines, tissue engineering, and cell therapy – including stem cells – have proven very promising. Nevertheless, prior to their introduction into routine clinical practice, large controlled clinical trials are required to assess the safety of these techniques.

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Section: Angiogenesis and Vasculogenesis In Chronic Woundsmentioning

confidence: 99%

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Pathogenesis of wound healing disorders in the elderly

Makrantonaki

Wlaschek

Scharffetter‐Kochanek

2017

J Deutsche Derma Gesell

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“…Diabetic foot ulcers (DFUs) represent a major complication of diabetes. DFUs are linked to cellular alterations that lead to impaired progenitor cell recruitment to the wound site (1)(2)(3)(4)(5), aberrant inflammatory cell infiltration (6,7), diminished extracellular matrix (ECM) production by fibroblasts (8,9), and compromised angiogenesis (10). Although our understanding of the pathophysiology of neuropathy and ischemia leading to DFUs has increased in recent years, existing therapies, such as growth factor treatment and nonintegrating bioactive dressings harboring naive fibroblasts, are not always successful (11).…”

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confidence: 99%

Differentiation of diabetic foot ulcer–derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes

et al. 2018

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Diabetic foot ulcers (DFUs) are a major complication of diabetes, and there is a critical need to develop novel cell- and tissue-based therapies to treat these chronic wounds. Induced pluripotent stem cells (iPSCs) offer a replenishing source of allogeneic and autologous cell types that may be beneficial to improve DFU wound-healing outcomes. However, the biologic potential of iPSC-derived cells to treat DFUs has not, to our knowledge, been investigated. Toward that goal, we have performed detailed characterization of iPSC-derived fibroblasts from both diabetic and nondiabetic patients. Significantly, gene array and functional analyses reveal that iPSC-derived fibroblasts from both patients with and those without diabetes are more similar to each other than were the primary cells from which they were derived. iPSC-derived fibroblasts showed improved migratory properties in 2-dimensional culture. iPSC-derived fibroblasts from DFUs displayed a unique biochemical composition and morphology when grown as 3-dimensional (3D), self-assembled extracellular matrix tissues, which were distinct from tissues fabricated using the parental DFU fibroblasts from which they were reprogrammed. In vivo transplantation of 3D tissues with iPSC-derived fibroblasts showed they persisted in the wound and facilitated diabetic wound closure compared with primary DFU fibroblasts. Taken together, our findings support the potential application of these iPSC-derived fibroblasts and 3D tissues to improve wound healing.-Kashpur, O., Smith, A., Gerami-Naini, B., Maione, A. G., Calabrese, R., Tellechea, A., Theocharidis, G., Liang, L., Pastar, I., Tomic-Canic, M., Mooney, D., Veves, A., Garlick, J. A. Differentiation of diabetic foot ulcer-derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes.

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“…Chronic M1 macrophage activation promotes tissue damage in neurodegenerative disorders, arthritis, and autoimmune diseases (12,15,16). Although necessary for the initial stages of tissue repair, excessive M1 activation inhibits the healing of damaged tissue through excessive matrix degradation and inhibition of tissue regeneration (17,18). Chronic M1 activation has also been shown to promote the development of cancer (19).…”

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confidence: 99%

Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory

Iwanowycz

Wang

Altomare

et al. 2016

Journal of Biological Chemistry

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Macrophages are pleiotropic cells capable of performing a broad spectrum of functions. Macrophage phenotypes are classified along a continuum between the extremes of proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. The seemingly opposing functions of M1 and M2 macrophages must be tightly regulated for an effective and proper response to foreign molecules or damaged tissue. Excessive activation of either M1 or M2 macrophages contributes to the pathology of many diseases. Emodin is a Chinese herb-derived compound and has shown potential to inhibit inflammation in various settings. In this study, we tested the ability of emodin to modulate the macrophage response to both M1 and M2 stimuli. Primary mouse macrophages were stimulated with LPS/IFN␥ or IL4 with or without emodin, and the effects of emodin on gene transcription, cell signaling pathways, and histone modifications were examined by a variety of approaches, including microarray, quantitative real-time PCR, Western blotting, chromatin immunoprecipitation, and functional assays. We found that emodin bidirectionally tunes the induction of LPS/IFN␥-and IL4-responsive genes through inhibiting NFB/IRF5/STAT1 signaling and IRF4/STAT6 signaling, respectively. Thereby, emodin modulates macrophage phagocytosis, migration, and NO production. Furthermore, emodin inhibited the removal of H3K27 trimethylation (H3K27m3) marks and the addition of H3K27 acetylation (H3K27ac) marks on genes required for M1 or M2 polarization of macrophages. In conclusion, our data suggest that emodin is uniquely able to suppress the excessive response of macrophages to both M1 and M2 stimuli and therefore has the potential to restore macrophage homeostasis in various pathologies.

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Myeloid cell dysfunction and the pathogenesis of the diabetic chronic wound

Cited by 79 publications

References 132 publications

Pathogenesis of wound healing disorders in the elderly

Pathogenesis of wound healing disorders in the elderly

Differentiation of diabetic foot ulcer–derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes

Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory

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