scholarly journals Extracellular-Vesicle-Based Coatings Enhance Bioactivity of Titanium Implants—SurfEV

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1445
Author(s):  
Taisa Nogueira Pansani ◽  
Thanh Huyen Phan ◽  
Qingyu Lei ◽  
Alexey Kondyurin ◽  
Bill Kalionis ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Titanium Surface ◽  
Wound Closure ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Tissue Growth ◽  
Titanium Implants ◽  
The Body ◽  
High Concentrations ◽  
And Migration

Extracellular vesicles (EVs) are nanoparticles released by cells that contain a multitude of biomolecules, which act synergistically to signal multiple cell types. EVs are ideal candidates for promoting tissue growth and regeneration. The tissue regenerative potential of EVs raises the tantalizing possibility that immobilizing EVs on implant surfaces could potentially generate highly bioactive and cell-instructive surfaces that would enhance implant integration into the body. Such surfaces could address a critical limitation of current implants, which do not promote bone tissue formation or bond bone. Here, we developed bioactive titanium surface coatings (SurfEV) using two types of EVs: secreted by decidual mesenchymal stem cells (DEVs) and isolated from fermented papaya fluid (PEVs). For each EV type, we determined the size, morphology, and molecular composition. High concentrations of DEVs enhanced cell proliferation, wound closure, and migration distance of osteoblasts. In contrast, the cell proliferation and wound closure decreased with increasing concentration of PEVs. DEVs enhanced Ca/P deposition on the titanium surface, which suggests improvement in bone bonding ability of the implant (i.e., osteointegration). EVs also increased production of Ca and P by osteoblasts and promoted the deposition of mineral phase, which suggests EVs play key roles in cell mineralization. We also found that DEVs stimulated the secretion of secondary EVs observed by the presence of protruding structures on the cell membrane. We concluded that, by functionalizing implant surfaces with specialized EVs, we will be able to enhance implant osteointegration by improving hydroxyapatite formation directly at the surface and potentially circumvent aseptic loosening of implants.

scholarly journals Reduced serum methods for contact-based coculture of human dermal fibroblasts and epidermal keratinocytes

BioTechniques ◽  
2020 ◽  
Vol 69 (5) ◽  
pp. 347-355
Author(s):  
Snehal Kadam ◽  
Madhusoodhanan Vandana ◽  
Karishma S Kaushik
Keyword(s):  
Wound Closure ◽  
Fetal Bovine Serum ◽  
Cell Types ◽  
High Serum ◽  
Dermal Fibroblasts ◽  
Epidermal Keratinocytes ◽  
Human Dermal Fibroblasts ◽  
Fetal Bovine ◽  
High Concentrations ◽  
Serum Free Conditions

Direct contact-based coculture of human dermal fibroblasts and epidermal keratinocytes has been a long-standing and challenging issue owing to different serum and growth factor requirements of the two cell types. Existing protocols employ high serum concentrations (up to 10% fetal bovine serum), complex feeder systems and a range of supplemental factors. These approaches are technically demanding and labor intensive, and pose scientific and ethical limitations associated with the high concentrations of animal serum. On the other hand, serum-free conditions often fail to support the proliferation of one or both cell types when they are cultured together. We have developed two reduced serum approaches (1–2% serum) that support the contact-based coculture of human dermal fibroblasts and immortalized keratinocytes and enable the study of cell migration and wound closure.

scholarly journals Gypenoside LXXV Promotes Cutaneous Wound Healing In Vivo by Enhancing Connective Tissue Growth Factor Levels Via the Glucocorticoid Receptor Pathway

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1595 ◽  
Author(s):  
Sungjoo Park ◽  
Eunsu Ko ◽  
Jun Hyoung Lee ◽  
Yoseb Song ◽  
Chang-Hao Cui ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Connective Tissue ◽  
Wound Closure ◽  
Tissue Growth ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
And Migration ◽  
Proliferation And Migration

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.

Matrix-fibrinogen enhances wound closure by increasing both cell proliferation and migration

Blood ◽  
2003 ◽  
Vol 102 (12) ◽  
pp. 4035-4043 ◽  
Author(s):  
Brian J. Rybarczyk ◽  
Sarah O. Lawrence ◽  
Patricia J. Simpson-Haidaris
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Wound Repair ◽  
Wound Closure ◽  
Mammary Epithelial Cells ◽  
Dermal Fibroblasts ◽  
Mammary Epithelial ◽  
Cell Phenotype ◽  
Matrix Assembly ◽  
And Migration

AbstractFibrinogen (FBG) assembles into matrix fibrils of fibroblasts, lung and mammary epithelial cells, but not endothelial cells. Furthermore, cryptic β15-21 residues are exposed in FBG fibrils with no evidence of thrombin or plasmin proteolysis. Herein, the effects of FBG on migration and proliferation of wounded dermal fibroblasts were investigated. FBG preassembled into matrix prior to scrape-wounding induced 3H-thymidine incorporation 8-fold and shortened the time to wound closure 1.6-fold ± 0.1-fold. FBG added immediately after wounding did not enhance either response. Fibroblast growth factor-2/platelet-derived growth factor (FGF-2/PDGF) stimulated cell proliferation 2.2-fold for FGF-2 and 3.2-fold for PDGF and wound closure 1.5-fold ± 0.1-fold in the absence of matrix-FBG. Surprisingly, exogenous growth factors had negligible effect on wound closure and cell proliferation already enhanced by matrix-FBG. Matrix-FBG-enhanced wound closure required active assembly of an FBG-fibronectin matrix, engagement of αvβ3, and FBG Aα-RGDS572-575 integrin recognition sites; Aα-RGDF95-98 sites were not sufficient for matrix-FBG assembly, enhanced wound closure, or cell proliferation. Although Bβ1-42 was not necessary for matrix assembly, it was required for matrix-FBG-enhanced cell migration. These data indicate that FBG serves as an important matrix constituent in the absence of fibrin formation to enhance wound repair and implicate Bβ1-42 as a physiologic inducer of signal transduction to promote an intermediate state of cell adhesion and a migratory cell phenotype. (Blood. 2003;102:4035-4043)

scholarly journals The CCN family: a new stimulus package

2003 ◽  
Vol 178 (2) ◽  
pp. 169-175 ◽  
Author(s):  
DR Brigstock
Keyword(s):  
Clinical Endocrinology ◽  
Cell Types ◽  
Tissue Growth ◽  
Ccn Proteins ◽  
Ccn Family ◽  
Igf Binding Proteins ◽  
Igf Binding ◽  
Multiple Cell ◽  
Activate Cell ◽  
And Migration

The CCN family comprises cysteine-rich 61 (CYR61/CCN1), connective tIssue growth factor (CTGF/CCN2), nephroblastoma overexpressed (NOV/CCN3), and Wnt-induced secreted proteins-1 (WISP-1/CCN4), -2 (WISP-2/CCN5) and -3 (WISP-3/CCN6). These proteins stimulate mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration of multiple cell types. Many of these activities probably occur through the ability of CCN proteins to bind and activate cell surface integrins. Accumulating evidence supports a role for these factors in endocrine pathways and endocrine-related processes. To illustrate the broad role played by the CCN family in basic and clinical endocrinology, this Article highlights the relationship between CCN proteins and hormone action, skeletal growth, placental angiogenesis, IGF-binding proteins and diabetes-induced fibrosis.

scholarly journals The essentials of developmental apoptosis

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 148 ◽  
Author(s):  
Anne K. Voss ◽  
Andreas Strasser
Keyword(s):  
Cell Proliferation ◽  
Functional Assessment ◽  
Fetal Development ◽  
Normal Tissue ◽  
Tissue Growth ◽  
The Body ◽  
Cell Populations ◽  
Embryonic And Fetal Development ◽  
Proliferation And Apoptosis ◽  
Hands And Feet

Apoptotic cells are commonly observed in a broad range of tissues during mammalian embryonic and fetal development. Specific requirements and functions of programmed cell death were inferred from early observations. These inferences did not hold up to functional proof for a requirement of apoptosis for normal tissue development in all cases. In this review, we summarize how the appraisal of the importance of developmental apoptosis has changed over the years, in particular with detailed functional assessment, such as by using gene-targeted mice lacking essential initiators or mediators of apoptosis. In recent years, the essentials of developmental apoptosis have emerged. We hypothesize that apoptosis is predominantly required to balance cell proliferation. The two interdependent processes—cell proliferation and apoptosis—together more powerfully regulate tissue growth than does each process alone. We proposed that this ensures that tissues and cell populations attain the appropriate size that allows fusion in the body midline and retain the size of cavities once formed. In addition, a limited number of tissues, albeit not all previously proposed, rely on apoptosis for remodeling, chiefly aortic arch remodeling, elimination of supernumerary neurons, removal of vaginal septa, and removal of interdigital webs in the formation of hands and feet.

scholarly journals Model-based data analysis of tissue growth in thin 3D printed scaffolds

2021 ◽  
Author(s):  
Alexander P Browning ◽  
Oliver J Maclaren ◽  
Pascal R Buenzli ◽  
Matthew Lanaro ◽  
Mark C Allenby ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Density ◽  
Reaction Diffusion ◽  
Tissue Growth ◽  
Reaction Diffusion Equation ◽  
Cell Behaviour ◽  
Model Based ◽  
3D Printed ◽  
And Migration ◽  
Proliferation And Migration

AbstractTissue growth in three-dimensional (3D) printed scaffolds enables exploration and control of cell behaviour in biologically realistic geometries. Cell proliferation and migration in these experiments have yet to be explicitly characterised, limiting the ability of experimentalists to determine the effects of various experimental conditions, such as scaffold geometry, on cell behaviour. We consider tissue growth by osteoblastic cells in melt electro-written scaffolds that comprise thin square pores with sizes that we deliberately vary. We collect highly detailed temporal measurements of the average cell density, tissue coverage, and tissue geometry. To quantify tissue growth in terms of the underlying cell proliferation and migration processes, we introduce and calibrate a mechanistic mathematical model based on the Porous-Fisher reaction-diffusion equation. Parameter estimates and uncertainty quantification through profile likelihood analysis reveal consistency in the rate of cell proliferation and steady-state cell density between pore sizes. This analysis also serves as an important model verification tool: while the use of reaction-diffusion models in biology is widespread, the appropriateness of these models to describe tissue growth in 3D scaffolds has yet to be explored. We find that the Porous-Fisher model is able to capture features relating to the cell density and tissue coverage, but is not able to capture geometric features relating to the circularity of the tissue interface. Our analysis identifies two distinct stages of tissue growth, suggests several areas for model refinement, and provides guidance for future experimental work that explores tissue growth in 3D printed scaffolds.Author SummaryAdvances in 3D printing technology have led to cell culture experiments that realistically capture natural biological environments. Despite the necessity of quantifying cell behaviour with parameters that can be compared between experiments, many existing mathematical models of tissue growth in these experiments neglect information relating to population size. We consider tissue growth by cells on 3D printed scaffolds that comprise square pores of various sizes in this work. We apply a relatively simple mathematical model based on the Porous-Fisher reaction-diffusion equation to interpret highly detailed measurements relating to both the cell density and the quantity of tissue deposited. We analyse the efficacy of such a model in capturing cell behaviour seen in the experiments and quantify cell behaviour in terms of parameters that carry a biologically meaningful interpretation. Our analysis identifies important areas for model refinement and provides guidance for future data-collection and experimentation that explores tissue growth in 3D printed scaffolds.

scholarly journals Seven Novel Genes Related to Cell Proliferation and Migration of VHL-Mutated Pheochromocytoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai Gao ◽  
Longfei Liu ◽  
Zhuolin Li ◽  
Yingxian Pang ◽  
Jiaqi Shi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Collagen Type ◽  
Tissue Growth ◽  
Cell Counting ◽  
Type I ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Pheochromocytoma, as a neuroendocrine tumor with the highest genetic correlation in all types of tumors, has attracted extensive attention. Von Hipper Lindau (VHL) has the highest mutation frequency among the genes associated with pheochromocytoma. However, the effect of VHL on the proteome of pheochromocytoma remains to be explored. In this study, the VHL knockdown (VHL-KD) PC12 cell model was established by RNA interference (shRNA). We compared the proteomics of VHL-KD and VHL-WT PC12 cell lines. The results showed that the expression of 434 proteins (VHL shRNA/WT > 1.3) changed significantly in VHL-KD-PC12 cells. Among the 434 kinds of proteins, 83 were involved in cell proliferation, cell cycle and cell migration, and so on. More importantly, among these proteins, we found seven novel key genes, including Connective Tissue Growth Factor (CTGF), Syndecan Binding Protein (SDCBP), Cysteine Rich Protein 61 (CYR61/CCN1), Collagen Type III Alpha 1 Chain (COL3A1), Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type V Alpha 2 Chain (COL5A2), and Serpin Family E Member 1 (SERPINE1), were overexpressed and simultaneously regulated cell proliferation and migration in VHL-KD PC12 cells. Furthermore, the abnormal accumulation of HIF2α caused by VHL-KD significantly increased the expression of these seven genes during hypoxia. Moreover, cell-counting, scratch, and transwell assays demonstrated that VHL-KD could promote cell proliferation and migration, and changed cell morphology. These findings indicated that inhibition of VHL expression could promote the development of pheochromocytoma by activating the expression of cell proliferation and migration associated genes.

scholarly journals c-Jun Overexpression Accelerates Wound Healing in Diabetic Rats by Human Umbilical Cord-Derived Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Chun Yue ◽  
Zi Guo ◽  
Yufang Luo ◽  
Jingjing Yuan ◽  
Xinxing Wan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Growth Factor ◽  
Wound Closure ◽  
Human Umbilical Cord ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
And Migration ◽  
Proliferation And Migration

Objective. Mesenchymal stem cells (MSCs) are considered a promising therapy for wound healing. Here, we explored the role of c-Jun in diabetic wound healing using human umbilical cord-derived MSCs (hUC-MSCs). Methods. Freshly isolated hUC-MSCs were subjected to extensive in vitro subcultivation. The cell proliferative and migratory capacities were assessed by the Cell Counting Kit-8 and scratch assays, respectively. c-Jun expression was evaluated by RT-PCR and western blot analysis. The function of c-Jun was investigated with lentivirus transduction-based gene silencing and overexpression. Diabetes mellitus was induced in SD rats on a high-glucose/fat diet by streptozocin administration. Wounds were created on the dorsal skin. The effects of c-Jun silencing and overexpression on wound closure by hUC-MSCs were examined. Reepithelialization and angiogenesis were assessed by histological and immunohistochemical analysis, respectively. Platelet-derived growth factor A (PDGFA), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) levels were determined by western blot analysis. Results. hUC-MSCs showed gradually decreased cell proliferation, migration, and c-Jun expression during subcultivation. c-Jun silencing inhibited cell proliferation and migration, while c-Jun overexpression enhanced proliferation but not migration. Compared with untransduced hUC-MSCs, local subcutaneous injection of c-Jun-overexpressing hUC-MSCs accelerated wound closure, enhanced angiogenesis and reepithelialization at the wound bed, and increased PDGFA and HGF levels in wound tissues. Conclusion. c-Jun overexpression promoted hUC-MSC proliferation and migration in vitro and accelerated diabetic wound closure, reepithelization, and angiogenesis by hUC-MSCs in vivo. These beneficial effects of c-Jun overexpression in diabetic wound healing by hUC-MSCs were at least partially mediated by increased PDGFA and HGF levels in wound tissues.

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