scholarly journals Fibroblasts close a void in free space by a purse-string mechanism

2020 ◽  
Author(s):  
Avelino Dos Santos Da Costa ◽  
Ramesh Subbiah ◽  
Seung Ja Oh ◽  
Hyun Tae Jeong ◽  
Jung-Im Na ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Tissue Repair ◽  
Wound Closure ◽  
Structural Features ◽  
Void Space ◽  
Free Standing ◽  
Purse String ◽  
Wound Site ◽  
Gap Closure ◽  
Closure Mechanism

AbstractHow stromal cells fill voids in wounded tissue remains one of the most fundamental questions in regenerative medicine. Fibroblasts are known to fill voids by depositing extracellular matrix (ECM) proteins while migrating towards the wound site; however, their ability to adopt an epithelial-like purse-string behaviour remains unexplored. Here, we fabricated an artificial wound with a deep void space to investigate fibroblasts’ behaviour during gap closure. We found that fibroblasts can form a free-standing bridge on deep microvoids and consequently close the void through the purse-string contraction, which was previously believed to be exclusively an epithelial wound closure mechanism. The results also revealed that the fibroblast gap closure in our fabricated 3D artificial wound depends on myosin II-mediated contractility and intercellular adherent junctions. Our study reveals that stromal cells can gain the structural features of epithelial cells, namely, intercellular contractile rings, to fulfil their functions under the specific microenvironmental conditions of tissue repair. Furthermore, fibroblasts can close artificial wounds with gap widths up to 300 μm, approximately twice as large as the critical epithelial gap closure size on non-adherent substrates. Fibroblasts exhibited a zip-up gap closure mechanism with a geometrical size effect. These findings reveal a new mechanism for gap closure by stromal cells during wound healing and pave a way to groundbreaking therapeutic strategies for tissue repair.

scholarly journals Actin-ring segment switching drives nonadhesive gap closure

2020 ◽  
Vol 117 (52) ◽  
pp. 33263-33271
Author(s):  
Qiong Wei ◽  
Xuechen Shi ◽  
Tiankai Zhao ◽  
Pingqiang Cai ◽  
Tianwu Chen ◽  
...  
Keyword(s):  
Large Scale ◽  
Traction Force ◽  
Collective Cell Migration ◽  
Actin Ring ◽  
Purse String ◽  
Actin Cable ◽  
Gap Closure ◽  
Actin Fiber ◽  
Ring Segment ◽  
Cable Segment

Gap closure to eliminate physical discontinuities and restore tissue integrity is a fundamental process in normal development and repair of damaged tissues and organs. Here, we demonstrate a nonadhesive gap closure model in which collective cell migration, large-scale actin-network fusion, and purse-string contraction orchestrate to restore the gap. Proliferative pressure drives migrating cells to attach onto the gap front at which a pluricellular actin ring is already assembled. An actin-ring segment switching process then occurs by fusion of actin fibers from the newly attached cells into the actin cable and defusion from the previously lined cells, thereby narrowing the gap. Such actin-cable segment switching occurs favorably at high curvature edges of the gap, yielding size-dependent gap closure. Cellular force microscopies evidence that a persistent rise in the radial component of inward traction force signifies successful actin-cable segment switching. A kinetic model that integrates cell proliferation, actin fiber fusion, and purse-string contraction is formulated to quantitatively account for the gap-closure dynamics. Our data reveal a previously unexplored mechanism in which cells exploit multifaceted strategies in a highly cooperative manner to close nonadhesive gaps.

Alginate hydrogel enriched with Ambystoma mexicanum epidermal lipoxygenase-loaded pectin nanoparticles for enhanced wound healing

2019 ◽  
Vol 34 (8) ◽  
pp. 1171-1187
Author(s):  
Farnoush Oveissi ◽  
Naser Tavakoli ◽  
Mohsen Minaiyan ◽  
Mohammad Reza Mofid ◽  
Azade Taheri
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Healing Process ◽  
Ambystoma Mexicanum ◽  
Wound Healing Process ◽  
Clinical Use ◽  
Sustained Delivery ◽  
Alginate Hydrogel ◽  
Wound Site ◽  
Minimal Scarring

Epidermal lipoxygenase enzyme extracted from Ambystoma mexicanum (AmbLOXe) is known to accelerate the wound-healing process. AmbLOXe as a protein suffers from inactivation and losing its activity during formulation. Therefore, a delivery system that protects AmbLOXe from inactivation and preserves its activity is needed. We prepared AmbLOXe-loaded pectin nanoparticles (AmbLOXe Pec-NPs) and placed them into an alginate hydrogel. AmbLOXe Pec-NPs incorporation into the alginate hydrogel provides a means for controlled and sustained delivery of AmbLOXe to the wound site. Furthermore, the suitable swelling behavior and mechanical properties of AmbLOXe Pec-NPs alginate hydrogel make it feasible for clinical use. AmbLOXe Pec-NPs alginate hydrogel significantly enhanced the wound-healing process on the rat full-thickness excisional wounds, increased the rate of wound closure, enhanced the re-epithelialization and decreased the incidence of abnormal scarring. AmbLOXe Pec-NPs alginate hydrogel can be proposed as an effective wound hydrogel for improving wound healing with minimal scarring.

scholarly journals A Regulatory miRNA–mRNA Network Is Associated with Tissue Repair Induced by Mesenchymal Stromal Cells in Acute Kidney Injury

2017 ◽  
Vol 7 ◽  
Author(s):  
Danilo Candido de Almeida ◽  
Ênio Jose Bassi ◽  
Hatylas Azevedo ◽  
Letícia Anderson ◽  
Clarice Silvia Taemi Origassa ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Kidney Injury

scholarly journals Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review

2020 ◽  
Vol 21 (3) ◽  
pp. 799 ◽  
Author(s):  
Joanna Lelek ◽  
Ewa K. Zuba-Surma
Keyword(s):  
Adipose Tissue ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Differentiation Potential

Mesenchymal stem/ stromal cells (MSCs) represent progenitor cells of various origin with multiple differentiation potential, representing the most studied population of stem cells in both in vivo pre-clinical and clinical studies. MSCs may be found in many tissue sources including extensively studied adipose tissue (ADSCs) and umbilical cord Wharton’s jelly (UC-MSCs). Most of sanative effects of MSCs are due to their paracrine activity, which includes also release of extracellular vesicles (EVs). EVs are small, round cellular derivatives carrying lipids, proteins, and nucleic acids including various classes of RNAs. Due to several advantages of EVs when compare to their parental cells, MSC-derived EVs are currently drawing attention of several laboratories as potential new tools in tissue repair. This review focuses on pro-regenerative properties of EVs derived from ADSCs and UC-MSCs. We provide a synthetic summary of research conducted in vitro and in vivo by employing animal models and within initial clinical trials focusing on neurological, cardiovascular, liver, kidney, and skin diseases. The summarized studies provide encouraging evidence about MSC-EVs pro-regenerative capacity in various models of diseases, mediated by several mechanisms. Although, direct molecular mechanisms of MSC-EV action are still under investigation, the current growing data strongly indicates their potential future usefulness for tissue repair.

scholarly journals Mesenchymal stem cells and their mitochondrial transfer: a double-edged sword

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Cheng Li ◽  
Marco K.H. Cheung ◽  
Shuo Han ◽  
Zhao Zhang ◽  
Ling Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Cancer Metastasis ◽  
Cell Injury ◽  
Tissue Degeneration ◽  
Cell Based Therapy ◽  
Mitochondrial Transfer

Abstract Mitochondrial dysfunction has been linked to many diseases including organ degeneration and cancer. Mesenchymal stem cells/stromal cells (MSCs) provide a valuable source for stem cell-based therapy and represent an emerging therapeutic approach for tissue regeneration. Increasing evidence suggests that MSCs can directly donate mitochondria to recover from cell injury and rescue mitochondrial damage-provoked tissue degeneration. Meanwhile, cancer cells and cancer stromal cells also cross-talk through mitochondrial exchange to regulate cancer metastasis. This review summarizes the research on MSCs and their mitochondrial transfer. It provides an overview of the biology, function, niches and signaling that play a role in tissue repair. It also highlights the pathologies of cancer growth and metastasis linked to mitochondrial exchange between cancer cells and surrounding stromal cells. It becomes evident that the function of MSC mitochondrial transfer is a double-edged sword. MSC mitochondrial transfer may be a pharmaceutical target for tissue repair and cancer therapy.

Mesenchymal stromal cells modulate tissue repair responses within the injured vocal fold

2019 ◽  
Vol 130 (1) ◽  
Author(s):  
Srinivasa Rao Nagubothu ◽  
Rachael V. Sugars ◽  
Nikolce Tudzarovski ◽  
Anton Törnqvist Andrén ◽  
Matteo Bottai ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Vocal Fold

scholarly journals Purse-String Versus Linear Conventional Skin Wound Closure of an Ileostomy: A Randomized Clinical Trial

2016 ◽  
Vol 32 (4) ◽  
pp. 144 ◽  
Author(s):  
Mina Alvandipour ◽  
Babak Gharedaghi ◽  
Hamed Khodabakhsh ◽  
Mohammad Yasin Karami
Keyword(s):  
Clinical Trial ◽  
Randomized Clinical Trial ◽  
Wound Closure ◽  
Skin Wound ◽  
Purse String

scholarly journals Enhancing the Migration Ability of Mesenchymal Stromal Cells by Targeting the SDF-1/CXCR4 Axis

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Leah A. Marquez-Curtis ◽  
Anna Janowska-Wieczorek
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Inflammatory Responses ◽  
Surface Expression ◽  
Trophic Factors ◽  
Migration Ability ◽  
Therapeutic Benefits

Mesenchymal stromal cells (MSCs) are currently being investigated in numerous clinical trials of tissue repair and various immunological disorders based on their ability to secrete trophic factors and to modulate inflammatory responses. MSCs have been shown to migrate to sites of injury and inflammation in response to soluble mediators including the chemokine stromal cell-derived factor-(SDF-)1, but during in vitro culture expansion MSCs lose surface expression of key homing receptors particularly of the SDF-1 receptor, CXCR4. Here we review studies on enhancement of SDF-1-directed migration of MSCs with the premise that their improved recruitment could translate to therapeutic benefits. We describe our studies on approaches to increase the CXCR4 expression in in vitro-expanded cord blood-derived MSCs, namely, transfection, using the commercial liposomal reagent IBAfect, chemical treatment with the histone deacetylase inhibitor valproic acid, and exposure to recombinant complement component C1q. These methodologies will be presented in the context of other cell targeting and delivery strategies that exploit pathways involved in MSC migration. Taken together, these findings indicate that MSCs can be manipulated in vitro to enhance their in vivo recruitment and efficacy for tissue repair.

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