Mechanical activation drives tenogenic differentiation of human mesenchymal stem cells in aligned dense collagen hydrogels

Tendons are force transmitting mechanosensitive tissues predominantly comprised of highly aligned collagen type I fibres. In this study, the recently introduced gel aspiration-ejection method was used to rapidly fabricate aligned dense collagen (ADC) hydrogel scaffolds. ADCs provide a biomimetic environment compared to traditional collagen hydrogels that are mechanically unstable and comprised of randomly oriented fibrils. The ADC scaffolds were shown to be anisotropic with comparable stiffness to immature tendons. Furthermore, the application of static and cyclic uniaxial loading, short-term (48 h) and high-strain (20%), resulted in a 3-fold increase in both the ultimate tensile strength and modulus of ADCs. Similar mechanical activation of human mesenchymal stem cell (MSC) seeded ADCs in serum- and growth factor-free medium induced their tenogenic differentiation. Both static and cyclic loading profiles resulted in a greater than 12-fold increase in scleraxis gene expression and either suppressed or maintained osteogenic and chondrogenic expressions. Following the 48 h mechanoactivation period, the MSC-seeded scaffolds were matured by tethering in basal medium without further external mechanical stimulation for 19 days, altogether making up 21 days of culture. Extensive cell-induced matrix remodeling and deposition of collagens type I and III, tenascin-C and tenomodulin were observed, where initial cyclic loading induced significantly higher tenomodulin protein content. Moreover, the initial short-term mechanical stimulation elongated and polarized seeded MSCs and overall cell alignment was significantly increased in those under static loading. These findings indicate the regenerative potential of the ADC scaffolds for short-term mechanoactivated tenogenic differentiation, which were achieved even in the absence of serum and growth factors that may potentially increase clinical translatability.

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Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short-Term Cyclic Stretching

Stem Cells International ◽

10.1155/2016/7342379 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 31

Author(s):

Janina Burk ◽

Amelie Plenge ◽

Walter Brehm ◽

Sandra Heller ◽

Bastian Pfeiffer ◽

...

Keyword(s):

Mechanical Stimulation ◽

Tendon Healing ◽

Cyclic Strain ◽

Matrix Remodeling ◽

Cell Alignment ◽

Cyclic Stretching ◽

Tenogenic Differentiation ◽

Custom Made ◽

Biomechanical Strength ◽

Made In

Tendon and ligament pathologies are still a therapeutic challenge, due to the difficulty in restoring the complex extracellular matrix architecture and biomechanical strength. While progress is being made in cell-based therapies and tissue engineering approaches, comprehensive understanding of the fate of progenitor cells in tendon healing is still lacking. The aim of this study was to investigate the effect of decellularized tendon matrix and moderate cyclic stretching as natural stimuli which could potentially direct tenogenic fate. Equine adipose-derived mesenchymal stromal cells (MSC) were seeded on decellularized tendon matrix scaffolds. Mechanical stimulation was applied in a custom-made cyclic strain bioreactor. Assessment was performed 4 h, 8 h, and 24 h following mechanical stimulation. Scaffold culture induced cell alignment and changes in expression of tendon-related genes, although cell viability was decreased compared to monolayer culture. Short mechanical stimulation periods enhanced most of the scaffold-induced effects. Collagen 1A2 expression levels were decreased, while collagen 3A1 and decorin levels were increased. Tenascin-C and scleraxis expression showed an initial decrease but had increased 24 h after stimulation. The results obtained suggest that decellularized tendon matrix, supported by cyclic stretching, can induce tenogenic differentiation and the synthesis of tendon components important for matrix remodeling.

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Effect of short-term antenatal dexamethasone administration on type I collagen synthesis and degradation in preterm infants at birth

Acta Paediatrica ◽

10.1080/08035250118565 ◽

2001 ◽

Vol 90 (8) ◽

pp. 921-925

Author(s):

T Saarela, J Risteli, A Kauppila, Mai

Keyword(s):

Preterm Infants ◽

Collagen Synthesis ◽

Type I Collagen ◽

Type I ◽

Short Term ◽

Synthesis And Degradation

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Short term mechanical stimulation using whole body vibration identifies differences in bone response between prepubertal boys with and without prior fracture

Bone Abstracts ◽

10.1530/boneabs.7.p25 ◽

2019 ◽

Author(s):

Rachel Harrison ◽

Kate Ward ◽

Alan Rigby ◽

Fatma Gossiel ◽

Nick Bishop

Keyword(s):

Mechanical Stimulation ◽

Whole Body Vibration ◽

Whole Body ◽

Short Term ◽

Body Vibration ◽

Bone Response ◽

Prior Fracture ◽

Prepubertal Boys

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Effects of long-term optimization and short-term deterioration of glycemic control on glucose counterregulation in type I diabetes mellitus

Diabetes ◽

10.2337/diabetes.33.4.394 ◽

1984 ◽

Vol 33 (4) ◽

pp. 394-400 ◽

Cited By ~ 8

Author(s):

G. Bolli ◽

P. De Feo ◽

S. De Cosmo ◽

G. Perriello ◽

G. Angeletti ◽

...

Keyword(s):

Diabetes Mellitus ◽

Glycemic Control ◽

Type I Diabetes ◽

Type I Diabetes Mellitus ◽

Type I ◽

Short Term

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Sustained normoglycemia in newly diagnosed type I diabetic subjects. Short-term effects and one-year follow-up

Diabetes ◽

10.2337/diabetes.33.10.995 ◽

1984 ◽

Vol 33 (10) ◽

pp. 995-1001 ◽

Cited By ~ 12

Author(s):

K. Perlman ◽

R. M. Ehrlich ◽

R. M. Filler ◽

A. M. Albisser

Keyword(s):

Type I ◽

Newly Diagnosed ◽

Short Term ◽

One Year ◽

Short Term Effects

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Non pharmacological high-intensity ultrasound treatment of human dermal fibroblasts to accelerate wound healing

Scientific Reports ◽

10.1038/s41598-021-81878-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jeong Yu Lee ◽

Dae-Jin Min ◽

Wanil Kim ◽

Bum-Ho Bin ◽

Kyuhan Kim ◽

...

Keyword(s):

Wound Healing ◽

High Intensity ◽

Mapk Pathway ◽

Dermal Fibroblasts ◽

Ultrasound Treatment ◽

Type I ◽

Human Dermal Fibroblasts ◽

Short Term ◽

High Intensity Ultrasound ◽

Extracellular Matrix Components

AbstractInspired by the effectiveness of low-intensity ultrasound on tissue regeneration, we investigated the potential effect of short-term high-intensity ultrasound treatment for acceleration of wound healing in an in vitro wound model and dermal equivalent, both comprising human dermal fibroblasts. Short-term ultrasound of various amplitudes significantly increased the proliferation and migration of fibroblasts and subsequently increased the production of the extracellular matrix components fibronectin and collagen type I, both of which are important for wound healing and are secreted by fibroblasts. In addition, ultrasound treatment increased the contraction of a fibroblast-embedded three-dimensional collagen matrix, and the effect was synergistically increased in the presence of TGF-β. RNA-sequencing and bioinformatics analyses revealed changes in gene expression and p38 and ERK1/2 MAPK pathway activation in the ultrasound-stimulated fibroblasts. Our findings suggest that ultrasound as a mechanical stimulus can activate human dermal fibroblasts. Therefore, the activation of fibroblasts using ultrasound may improve the healing of various types of wounds and increase skin regeneration.

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The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽

10.3390/cells10051046 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1046

Author(s):

Jorge Martinez ◽

Patricio C. Smith

Keyword(s):

Extracellular Matrix ◽

Type I Collagen ◽

Cell Metabolism ◽

Breast Tumors ◽

Extracellular Matrix Remodeling ◽

Type I ◽

Matrix Remodeling ◽

Desmoplastic Reaction ◽

The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

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Browning of White Adipocytes in Fat Grafts Associated with Higher Level of Necrosis and Type 2 Macrophages Recruitment

Aesthetic Surgery Journal ◽

10.1093/asj/sjab144 ◽

2021 ◽

Author(s):

Tong Liu ◽

Su Fu ◽

Qian Wang ◽

Hao Cheng ◽

Dali Mu ◽

...

Keyword(s):

Fold Increase ◽

Chow Diet ◽

Sham Operation ◽

Type I ◽

Electronic Microscopy ◽

Fat Transfer ◽

Fat Grafts ◽

Female Nude ◽

Normal Chow

Abstract Background Induced browning adipocytes were assumed less viable and more prone to necrosis for their hypermetabolic property. Our previous study showed that browning of adipocytes was more evident in fat grafts with necrosis in humans. Objectives We aimed to estimate whether fat-transfer-induced browning biogenesis was associated with necrosis and its potential inflammation mechanisms in murine models. Methods Human subcutaneous adipose from thigh or abdomen of 5 patients via liposuction were injected in 100µl or 500µl (n=20 per group) into the dorsal flank of 6-8-week female nude mice fed with normal chow diet, and harvested after 2, 4, 8 and 12 weeks. Control groups did not receive any grafting procedures (sham operation), where lipoaspirates were analyzed immediately after harvest. Histology and electronic microscopy, immunological analyses of browning markers, necrosis marker, and type I/II macrophages markers in mice were performed. Results Histology and electronic microscopy showed browning adipocytes in in fat grafts with higher level of necrosis (0.435±0.017pg/ml for cleaved caspase-3, **p<0.01), IL-6(749.0±134.1pg/ml,***p<0.001) and infiltration of type 2 macrophage profiles in mice(2-fold increase, *p<0.05). Conclusions Browning of adipocytes induced by fat transfer in mice is in parallel with post-grafting necrotic levels, associated with elevated IL-6 and activated M2 macrophages profiles which promote browning development.

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Adrenergic control of vascular resistance varies in muscles composed of different fiber types: influence of the vascular endothelium

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00205.2011 ◽

2011 ◽

Vol 301 (3) ◽

pp. R783-R790 ◽

Cited By ~ 26

Author(s):

Bradley J. Behnke ◽

Robert B. Armstrong ◽

Michael D. Delp

Keyword(s):

Blood Flow ◽

Vascular Resistance ◽

Vascular Endothelium ◽

Fold Increase ◽

Male Rats ◽

Type I ◽

Fiber Types ◽

Fast Twitch Muscle ◽

Dose Responses ◽

Fast Twitch

The influence of the sympathetic nervous system (SNS) upon vascular resistance is more profound in muscles comprised predominately of low-oxidative type IIB vs. high-oxidative type I fiber types. However, within muscles containing high-oxidative type IIA and IIX fibers, the role of the SNS on vasomotor tone is not well established. The purpose of this study was to examine the influence of sympathetic neural vasoconstrictor tone in muscles composed of different fiber types. In adult male rats, blood flow to the red and white portions of the gastrocnemius (GastRed and GastWhite, respectively) and the soleus muscle was measured pre- and postdenervation. Resistance arterioles from these muscles were removed, and dose responses to α1-phenylephrine or α2-clonidine adrenoreceptor agonists were determined with and without the vascular endothelium. Denervation resulted in a 2.7-fold increase in blood flow to the soleus and GastRed and an 8.7-fold increase in flow to the GastWhite. In isolated arterioles, α2-mediated vasoconstriction was greatest in GastWhite (∼50%) and less in GastRed (∼31%) and soleus (∼17%); differences among arterioles were abolished with the removal of the endothelium. There was greater sensitivity to α1-mediated vasoconstriction in the GastWhite and GastRed vs. the soleus, which was independent of whether the endothelium was present. These data indicate that 1) control of vascular resistance by the SNS in high-oxidative, fast-twitch muscle is intermediate to that of low-oxidative, fast-twitch and high-oxidative, slow-twitch muscles; and 2) the ability of the SNS to control blood flow to low-oxidative type IIB muscle appears to be mediated through postsynaptic α1- and α2-adrenoreceptors on the vascular smooth muscle.

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