Enhanced Healing of Diabetic Wounds by Topical Administration of Adipose Tissue-Derived Stromal Cells Overexpressing Stromal-Derived Factor-1: Biodistribution and Engraftment Analysis by Bioluminescent Imaging

Chronic ulcers represent a major health problem in diabetic patients resulting in pain and discomfort. Conventional therapy does not guarantee adequate wound repair. In diabetes, impaired healing is partly due to poor endothelial progenitor cells mobilisation and homing, with altered levels of the chemokine stromal-derived factor-1 (SDF-1) at the wound site. Adipose tissue-associated stromal cells (AT-SCs) can provide an accessible source of progenitor cells secreting proangiogenic factors and differentiating into endothelial-like cells. We demonstrated that topical administration of AT-SCs genetically modifiedex vivoto overexpress SDF-1, promotes wound healing into diabetic mice. In particular, byin vivobioluminescent imaging analysis, we monitored biodistribution and survival after transplantation of luciferase-expressing cells. In conclusion, this study indicates the therapeutic potential of AT-SCs administration in wound healing, through cell differentiation, enhanced cellular recruitment at the wound site, and paracrine effects associated with local growth-factors production.

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Relevance of Thoracic Adipose Tissue in Wound Healing Disorder of Diabetic Patients

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0035-1544520 ◽

2015 ◽

Vol 63 (S 01) ◽

Author(s):

J. Andres ◽

C. Dittfeld ◽

A. Jannasch ◽

K. Plötze ◽

T. Waldow ◽

...

Keyword(s):

Wound Healing ◽

Adipose Tissue ◽

Diabetic Patients

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Augmentation of Dermal Wound Healing by Adipose Tissue-Derived Stromal Cells (ASC)

Bioengineering ◽

10.3390/bioengineering5040091 ◽

2018 ◽

Vol 5 (4) ◽

pp. 91 ◽

Cited By ~ 5

Author(s):

Joris van Dongen ◽

Martin Harmsen ◽

Berend van der Lei ◽

Hieronymus Stevens

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Adipose Tissue ◽

Stromal Cells ◽

Randomized Clinical Trials ◽

Cell Types ◽

Matrix Remodeling ◽

Skin Wound Healing ◽

Dermal Wound Healing ◽

Dermal Wound

The skin is the largest organ of the human body and is the first line of defense against physical and biological damage. Thus, the skin is equipped to self-repair and regenerates after trauma. Skin regeneration after damage comprises a tightly spatial-temporally regulated process of wound healing that involves virtually all cell types in the skin. Wound healing features five partially overlapping stages: homeostasis, inflammation, proliferation, re-epithelization, and finally resolution or fibrosis. Dysreguled wound healing may resolve in dermal scarring. Adipose tissue is long known for its suppressive influence on dermal scarring. Cultured adipose tissue-derived stromal cells (ASCs) secrete a plethora of regenerative growth factors and immune mediators that influence processes during wound healing e.g., angiogenesis, modulation of inflammation and extracellular matrix remodeling. In clinical practice, ASCs are usually administered as part of fractionated adipose tissue i.e., as part of enzymatically isolated SVF (cellular SVF), mechanically isolated SVF (tissue SVF), or as lipograft. Enzymatic isolation of SVF obtained adipose tissue results in suspension of adipocyte-free cells (cSVF) that lack intact intercellular adhesions or connections to extracellular matrix (ECM). Mechanical isolation of SVF from adipose tissue destructs the parenchyma (adipocytes), which results in a tissue SVF (tSVF) with intact connections between cells, as well as matrix. To date, due to a lack of well-designed prospective randomized clinical trials, neither cSVF, tSVF, whole adipose tissue, or cultured ASCs can be indicated as the preferred preparation procedure prior to therapeutic administration. In this review, we present and discuss current literature regarding the different administration options to apply ASCs (i.e., cultured ASCs, cSVF, tSVF, and lipografting) to augment dermal wound healing, as well as the available indications for clinical efficacy.

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Evaluation of subcutaneous drainage system versus tissue re-approximation alone using Pfannenstiel incision in obese females undergoing caesarean section.

10.21203/rs.3.rs-170188/v1 ◽

2021 ◽

Author(s):

Safaa A. Ibrahim ◽

Mena M. Abdalla ◽

Rofida M. Elshafei

Keyword(s):

Wound Healing ◽

Adipose Tissue ◽

Caesarean Section ◽

Drainage System ◽

Negative Effects ◽

Major Health Problem ◽

Major Health ◽

Pfannenstiel Incision ◽

System Versus ◽

Minor Ailments

Abstract Obesity is a growing problem and a major health problem. In 1919, Dr. Kelly described obesity by saying that "to be a storehouse for useless adipose tissue and to carry this handicap around, openly displayed wherever one goes, is one of most distressing of life's minor ailments." It has complex negative effects on the functions and procedures of various organs, and includes problems relating to wound healing .

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964. Enhanced Healing of Diabetic Wounds by Topical Administration of Genetically Modified Adipose Tissue-Derived Stromal Cells

Molecular Therapy ◽

10.1016/s1525-0016(16)40367-9 ◽

2008 ◽

Vol 16 ◽

pp. S359

Keyword(s):

Adipose Tissue ◽

Stromal Cells ◽

Genetically Modified ◽

Topical Administration ◽

Diabetic Wounds

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Effects of dapagliflozin on human epicardial adipose tissue: modulation of insulin resistance, inflammatory chemokine production, and differentiation ability

Cardiovascular Research ◽

10.1093/cvr/cvx186 ◽

2017 ◽

Vol 114 (2) ◽

pp. 336-346 ◽

Cited By ~ 43

Author(s):

Esther Díaz-Rodríguez ◽

Rosa M Agra ◽

Ángel L Fernández ◽

Belén Adrio ◽

Tomás García-Caballero ◽

...

Keyword(s):

Insulin Resistance ◽

Cardiovascular Disease ◽

Wound Healing ◽

Endothelial Cells ◽

Adipose Tissue ◽

Glucose Uptake ◽

Epicardial Adipose Tissue ◽

Diabetic Patients ◽

Chemokine Production ◽

Inflammatory Chemokines

AbstractAimsIn patients with cardiovascular disease, epicardial adipose tissue (EAT) is characterized by insulin resistance, high pro-inflammatory chemokines, and low differentiation ability. As dapagliflozin reduces body fat and cardiovascular events in diabetic patients, we would like to know its effect on EAT and subcutaneous adipose tissue (SAT).Methods and resultsAdipose samples were obtained from 52 patients undergoing heart surgery. Sodium-glucose cotransporter 2 (SGLT2) expression was determined by real-time polymerase chain reaction (n = 20), western blot, and immunohistochemistry. Fat explants (n = 21) were treated with dapagliflozin and/or insulin and glucose transporters expression measured. Glucose, free fatty acid, and adipokine levels (by array) were measured in the EAT secretomes, which were then tested on human coronary endothelial cells using wound healing assays. Glucose uptake was also measured using the fluorescent glucose analogue (6NBDG) in differentiated stromal vascular cells (SVCs) from the fat pads (n = 11). Finally, dapagliflozin-induced adipocyte differentiation was assessed from the levels of fat droplets (AdipoRed staining) and of perilipin. SGLT2 was expressed in EAT. Dapagliflozin increased glucose uptake (20.95 ± 4.4 mg/dL vs. 12.97 ± 4.1 mg/dL; P < 0.001) and glucose transporter type 4 (2.09 ± 0.3 fold change; P < 0.01) in EAT. Moreover, dapagliflozin reduced the secretion levels of chemokines and benefited wound healing in endothelial cells (0.21 ± 0.05 vs. 0.38 ± 0.08 open wound; P < 0.05). Finally, chronic treatment with dapagliflozin improved the differentiation of SVC, confirmed by AdipoRed staining [539 ± 142 arbitrary units (a.u.) vs. 473 ± 136 a.u.; P < 0.01] and perilipin expression levels (121 ± 10 vs. 84 ± 11 a.u.).ConclusionsDapagliflozin increased glucose uptake, reduced the secretion of pro-inflammatory chemokines (with a beneficial effect on the healing of human coronary artery endothelial cells), and improved the differentiation of EAT cells. These results suggest a new protective pathway for this drug on EAT from patients with cardiovascular disease.

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Cell Therapy Based on Adipose Tissue-Derived Stromal Cells Promotes Physiological and Pathological Wound Healing

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.108.178962 ◽

2009 ◽

Vol 29 (4) ◽

pp. 503-510 ◽

Cited By ~ 191

Author(s):

T.G. Ebrahimian ◽

F. Pouzoulet ◽

C. Squiban ◽

V. Buard ◽

M. André ◽

...

Keyword(s):

Wound Healing ◽

Adipose Tissue ◽

Cell Therapy ◽

Stromal Cells

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Accelerated Wound Healing in Healing-Impaired db/db Mice by Autologous Adipose Tissue-Derived Stromal Cells Combined With Atelocollagen Matrix

Yearbook of Surgery ◽

10.1016/s0090-3671(09)79579-5 ◽

2010 ◽

Vol 2010 ◽

pp. 203-204

Author(s):

J.M. Daly

Keyword(s):

Wound Healing ◽

Adipose Tissue ◽

Stromal Cells

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Functionalized extracellular matrix scaffolds loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing

10.1101/2021.02.02.429318 ◽

2021 ◽

Author(s):

Siqi He ◽

Tanaya Walimbe ◽

Hongyuan Chen ◽

Kewa Gao ◽

Priyadarsini Kumar ◽

...

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Cyclic Peptide ◽

Skin Flap ◽

Integrin Αvβ3 ◽

Limb Amputation ◽

Diabetic Patients ◽

Endothelial Progenitor

AbstractDiabetic ischemic wound treatment remains a critical clinical challenge. Strategies that enhance angiogenesis and improve ischemic pathology may promote the healing of poor wounds, particularly diabetic wounds in highly ischemic condition. We previously identified a cyclic peptide LXW7 that specifically binds to integrin αvβ3 on endothelial progenitor cells (EPCs) and endothelial cells (ECs), activates VEGF receptors, and promotes EC growth and maturation. In this study, we designed and synthesized a pro-angiogenic molecule LXW7-DS-SILY by conjugating LXW7 to a collagen-binding proteoglycan mimetic DS-SILY and further employed this novel bifunctional ligand to functionalize extracellular matrix (ECM) scaffolds, promote neovascularization and accelerate ischemic wound healing. We established a Zucker Diabetic Fatty (ZDF) rat ischemic skin flap model and found the wounds treated by LXW7-DS-SILY-functionalized ECM scaffolds, with or without EPCs, significantly improved wound healing, enhanced neovascularization and modulated collagen fibrillogenesis. These functionalized ECM scaffolds also significantly promoted EPC attachment, growth and survival in the ischemic environment. Altogether, this study provides a promising novel treatment to accelerate diabetic ischemic wound healing, thereby reducing limb amputation and mortality of diabetic patients.

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