Migration Of Mesenchymal Cells Research Articles

Platelet-Rich Plasma Lysate-Incorporating Gelatin Hydrogel as a Scaffold for Bone Reconstruction.

In implant dentistry, large vertical and horizontal alveolar ridge deficiencies in mandibular and maxillary bone are challenges that clinicians continue to face. One of the limitations of porous blocks for reconstruction of bone in large defects in the oral cavity, and in the musculoskeletal system, is that fibrin clot does not adequately fill the interior pores and does not persist long enough to accommodate cell migration into the center of the block. The objective of our work was to develop a gelatin-based gel incorporating platelet-rich plasma (PRP) lysate, to mimic the role that a blood clot would normally play to attract and accommodate the migration of host osteoprogenitor and endothelial cells into the scaffold, thereby facilitating bone reconstruction. A conjugate of gelatin (Gtn) and hydroxyphenyl propionic acid (HPA), an amino-acid-like molecule, was commended for this application because of its ability to undergo enzyme-mediated covalent cross-linking to form a hydrogel in vivo, after being injected as a liquid. The initiation and propagation of cross-linking were under the control of horseradish peroxidase and hydrogen peroxide, respectively. The objectives of this in vitro study were directed toward evaluating: (1) the migration of rat mesenchymal stem cells (MSCs) into Gtn–HPA gel under the influence of rat PRP lysate or recombinant platelet-derived growth factor (PDGF)-BB incorporated into the gel; (2) the differentiation of MSCs, incorporated into the gel, into osteogenic cells under the influence of PRP lysate and PDGF-BB; and (3) the release kinetics of PDGF-BB from gels incorporating two formulations of PRP lysate and recombinant PDGF-BB. Results: The number of MSCs migrating into the hydrogel was significantly (3-fold) higher in the hydrogel group incorporating PRP lysate compared to the PDGF-BB and the blank gel control groups. For the differentiation/osteogenesis assay, the osteocalcin-positive cell area percentage was significantly higher in both the gel/PRP and gel/PDGF-BB groups, compared to the two control groups: cells in the blank gels grown in cell expansion medium and in osteogenic medium. Results of the ELISA release assay indicated that Gtn–HPA acted as an effective delivery vehicle for the sustained release of PDGF-BB from two different PRP lysate batches, with about 60% of the original PDGF-BB amount in the two groups remaining in the gel at 28 days. Conclusions: Gtn–HPA accommodates MSC migration. PRP-lysate-incorporating hydrogels chemoattract increased MSC migration into the Gtn–HPA compared to the blank gel. PRP-lysate- and the PDGF-BB-incorporating gels stimulate osteogenic differentiation of the MSCs. The release of the growth factors from Gtn–HPA containing PRP lysate can extend over the period of time (weeks) necessary for bone reconstruction. The findings demonstrate that Gtn–HPA can serve as both a scaffold for cell migration and a delivery vehicle that allows sustained and controlled release of the incorporated therapeutic agent over extended periods of time. These findings commend Gtn–HPA incorporating PRP lysate for infusion into porous calcium phosphate blocks for vertical and horizontal ridge reconstruction, and for other musculoskeletal applications.

The effect of Klotho protein complexed with nanomaterials on bone mesenchymal stem cell performance in the treatment of diabetic ischaemic ulcer.

A lack of angiogenesis is the key problem in the healing of diabetic foot ulcers. Stem cells have already been proven to have a high potential for angiogenesis. The most important aspects of stem cell therapy are improving the microenvironment, cell homing and continuous factor stimulation. We investigated the effect of Klotho protein to heal wounds by promoting the proliferation and migration of bone mesenchymal stem cells and endothelial cells in vitro. Based on the above study, we produced a compound material by using poly(lactic-co-glycolic acid) (PLGA), chitosan microspheres and gelatin through electro spining technology. The structure of the compound material, just like a sandwich, is that two pieces of PLGA nanofiber films clamped gelatin film which contained chitosan microspheres. In the in vitro release experiment, we could detect the release of Klotho after seven days in the compound material, but the release time was approximately 40 hours for the chitosan microspheres. After seeded bone mesenchymal stem cells (BMSCs) on the surface of the compound material, we observed morphologies of the chitosan microsphere, the PLGA nanofiber and BMSCs by scanning electron microscopy. The nanofiber mesh biological tissue materials could supply an appropriate microenvironment and cell factors for the survival of BMSCs. Compared with the control group, the biological tissue material seeded with BMSCs significantly promoted angiogenesis in the lower limb of diabetic C57BL/6J mice and accelerated diabetic foot wound healing. The compound biomaterial which could continuously stimulate BMSCs through releasing Klotho protein could accelerate wound healing in the diabetic foot and other ischemic ulcers.

Aptamer/Hydroxyapatite-Functionalized Titanium Substrate Promotes Implant Osseointegration via Recruiting Mesenchymal Stem Cells.

Endowing bone regeneration materials with both stem cell recruitment and osteoinduction properties is a key factor in promoting osseointegration of titanium (Ti) implants. In this study, Apt19s-grafted oxidized hyaluronic acid (OHA) was deposited onto a protein-mediated biomineralization hydroxyapatite (HAp) coating of Ti. HAp was achieved by the treatment of lysozyme and tris(2-carboxyethyl) phosphonate mixture and then soaked in calcium ion (Ca2+) solution to obtain functional Ti substrate (Ti/HAp/OHA-Apt). In vitro studies confirmed that Ti/HAp/OHA-Apt could effectively maintain the sustained release of Apt19s from Ti for 7 days. The released Apt19s significantly enhanced the migration of bone marrow mesenchymal stem cells (MSCs), which was reflected by the experiment of transwell assay, wound healing, and zymogram detection. Compared with pure Ti, Ti/HAp/OHA-Apt was able to adjust the adsorption of functional proteins at the Ti-based interface to expose their active sites, which significantly increased the expression of adhesion-associated proteins (vinculin and tensin) in MSCs to promote their adhesion on Ti-based interface. In vitro cell experiments of alkaline phosphatase activity staining, mineralization detection, and expression of osteogenesis-related genes showed that Ti/HAp/OHA-Apt significantly enhanced the osteogenic differentiation ability of MSCs, which may be highly related to the porous structure of hydroxyapatite on Ti interface. In vivo test of Micro-CT, H&E staining, and histochemical staining further confirmed that Ti/HAp/OHA-Apt was able to promote MSC recruitment at the peri-implant interface to form new bone. This work provides a new approach to develop functional Ti-based materials for bone defect repair.

Live imaging of echinoderm embryos to illuminate evo-devo.

Echinoderm embryos have been model systems for cell and developmental biology for over 150 years, in good part because of their optical clarity. Discoveries that shaped our understanding of fertilization, cell division and cell differentiation were only possible because of the transparency of sea urchin eggs and embryos, which allowed direct observations of intracellular structures. More recently, live imaging of sea urchin embryos, coupled with fluorescence microscopy, has proven pivotal to uncovering mechanisms of epithelial to mesenchymal transition, cell migration and gastrulation. However, live imaging has mainly been performed on sea urchin embryos, while echinoderms include numerous experimentally tractable species that present interesting variation in key aspects of morphogenesis, including differences in embryo compaction and mechanisms of blastula formation. The study of such variation would allow us not only to understand how tissues are formed in echinoderms, but also to identify which changes in cell shape, cell-matrix and cell-cell contact formation are more likely to result in evolution of new embryonic shapes. Here we argue that adapting live imaging techniques to more echinoderm species will be fundamental to exploit such an evolutionary approach to the study of morphogenesis, as it will allow measuring differences in dynamic cellular behaviors - such as changes in cell shape and cell adhesion - between species. We briefly review existing methods for live imaging of echinoderm embryos and describe in detail how we adapted those methods to allow long-term live imaging of several species, namely the sea urchin Lytechinus pictus and the sea stars Patiria miniata and Patiriella regularis. We outline procedures to successfully label, mount and image early embryos for 10–16 h, from cleavage stages to early blastula. We show that data obtained with these methods allows 3D segmentation and tracking of individual cells over time, the first step to analyze how cell shape and cell contact differ among species. The methods presented here can be easily adopted by most cell and developmental biology laboratories and adapted to successfully image early embryos of additional species, therefore broadening our understanding of the evolution of morphogenesis.

MiR-31 improves spinal cord injury in mice by promoting the migration of bone marrow mesenchymal stem cells.

Stem cell transplantation therapy is a potential approach for the repair of spinal cord injuries and other neurodegenerative diseases, but its effectiveness is hampered by the low rate of targeted migration of cells to the area of injury. The aim of this study was to investigate the effects of miR-31 on the migration of bone marrow mesenchymal stem cells (BMSCs) and the regulation of MMP-2 and CXCR4 expression in vitro and in vivo. eGFP-expressing BMSCs were isolated and cultured for subsequent experiments. The experiments were divided into three groups: control group, miR-31agomir group, and miR-31antagomir group. Proliferation was analyzed using CCK-8 and flow cytometry; cell migration in vitro was analyzed using wound-healing and transwell assays. The mouse SCI model was prepared by the impact method, and cells were transplanted (3 groups, 12 per group). Relevant inflammatory factors were detected by ELISA. The BMS score was used to evaluate the functional recovery of the mouse spinal cord and the frozen section was used to analyze the cell migration ability in vivo. The in vitro and in vivo expression levels of MMP-2 and CXCR4 were evaluated by Western blot and immunohistochemical staining. In vitro experiments showed that cells in the miR-31agomir group exhibited enhanced cell proliferation (P<0.05, P<0.001) and migration (P<0.001) and upregulated protein expression levels of CXCR4 (P<0.01) and MMP-2 (P<0.001) compared with cells in the control group. The results of in vivo experiments showed that the expression of pro-inflammatory factors was reduced after cell transplantation treatment. Cells in the miR-31agomir group showed enhanced cell-targeted migration ability (P<0.001), improved the function of damaged tissues (P<0.001), and upregulated CXCR4 and MMP-2 expression compared to the control group (P<0.001). Our experiment demonstrated that miR-31 could promote the migration of BMSCs and miR-31 could repair and improve the function of damaged tissues in SCI.

Physiology-Inspired Multilayer Nanofibrous Membranes Modulating Endogenous Stem Cell Recruitment and Osteo-Differentiation for Staged Bone Regeneration.

Bone regeneration involves a cascade of sophisticated, multiple-staged cellular and molecular events, where early-phase stem cell recruitment mediated by chemokines and late-phase osteo-differentiation induced by pro-osteogenic factors play the crucial roles. Herein, enlightened by a bone physiological and regenerative mechanism, the multilayer nanofibrous membranes (PLLA@SDF-1α@MT01) consisting of PLLA/MT01 micro-sol electrospun nanofibers as intima and PLLA/PEG/SDF-1α electrospun nanofibers as adventitia are fabricated through micro-sol electrospinning and manual multi-layer stacking technologies. In vitro releasing profiles show that PLLA@SDF-1α@MT01 represents the rapid release of stromal cell-derived SDF-1α(SDF-1α) in the outer layers, while with long-term sustained release of MT01 in the inner layer. Owing to interconnected porosity like the natural bone extracellular matrix and improved hydrophilia, PLLA@SDF-1α@MT01 manifests good biocompatibility both in vitro and in vivo. Furthermore, PLLA@SDF-1α@MT01 can promote bone marrow mesenchymal stem cells (BMSCs) migration by amplifying the SDF-1α/CXCR4 axis and stimulating BMSCs osteo-differentiation via activating the MAPK pathway in vitro. PLLA@SDF-1α@MT01, with a programmed dual-delivery system, exhibits the synergetic promotion of bone regeneration and vascularization by emulating key characteristics of the staged bone repair in vivo. Overall, PLLA@SDF-1α@MT01 that mimics the endogenous cascades of bone regeneration can enrich the physiology-mimetic staged regenerative strategy and represent a promising tissue-engineered scaffold for the bone defect.

Bioactive Vitamin D Attenuates MED28-Mediated Cell Growth and Epithelial–Mesenchymal Transition in Human Colorectal Cancer Cells

Inadequate vitamin D status may increase the risk of developing multiple types of cancer. Epidemiological studies suggest an inverse association between 25-hydroxyvitamin D3 (25(OH)D3) and malignancy, including colorectal cancer. Previous studies have suggested that MED28, a Mediator subunit involved in transcriptional regulation, is associated with the growth of colorectal cancer cells; however, its role in the progression of metastasis such as epithelial–mesenchymal transition (EMT) and cell migration of colorectal cancer is unclear at present. The aim of this study was to investigate a potentially suppressive effect of calcitriol, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), a bioactive form of vitamin D, and the role of MED28 in the progression of EMT in human colorectal cancer cells. Suppression of MED28 increased the expression of E-cadherin and reduced the expression of several mesenchymal and migration biomarkers and Wnt/β-catenin signaling molecules, whereas overexpression of MED28 enhanced the EMT features. Calcitriol suppressed the expression of MED28, and the effect of calcitriol mirrored that of MED28 silencing. Our data indicate that calcitriol attenuated MED28-mediated cell growth and EMT in human colorectal cancer cells, underlining the significance of MED28 in the progression of colorectal cancer and supporting the potential translational application of calcitriol.

Neuritin Promotes Bone Marrow-Derived Mesenchymal Stem Cell Migration to Treat Diabetic Peripheral Neuropathy.

The purpose of this study is to explore the effect and mechanism of neuritin overexpression in the bone marrow on peripheral neuropathy in type 2 diabetic (db/db) mice. We analyzed the impact of bone marrow neuritin overexpression on diabetic peripheral neuropathy and migration of bone marrow mesenchymal stem cells in db/db mice. Antagonists were used to inhibit the stromal cell-derived factor (SDF)-1α/C-X-C chemokine receptor type 4 (CXCR4)-phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in primary cultured bone marrow mesenchymal stem cells. Immunofluorescence, transmission electron microscopy, Oil Red O staining, and transwell migration assays were used. Bone marrow-specific overexpression of neuritin in db/db mice was successfully established. Overexpression of neuritin in the bone marrow ameliorated hyperglycemia, prevented diabetic peripheral neuropathy, protected the ultrastructure of the sciatic nerve and intra-epidermal nerve fiber density, and promoted Schwann cell proliferation and remyelination in the sciatic nerve. Moreover, it ameliorated fat accumulation, adipocyte number, and vascular and nerve densities; decreased glutamate content in serum and bone marrow; restored gradient SDF-1α contents between bone marrow, blood, and sciatic nerve; and promoted impaired diabetic bone marrow mesenchymal stem cell migration. Neuritin improves bone marrow mesenchymal stem cell migration via the SDF-1α/CXCR4-PI3K/Akt signaling pathway in vitro. Overexpression of neuritin in the bone marrow can locally ameliorate neuropathy in the bone marrow. This improves the migration capability of bone marrow mesenchymal stem cells and repairs diabetic peripheral neuropathy, at least partly by activating the PI3K/Akt pathway through the SDF-1α/CXCR4 axis.

Recurrent NOMO1 Gene Deletion Is a Potential Clinical Marker in Early-Onset Colorectal Cancer and Is Involved in the Regulation of Cell Migration.

Simple SummaryThe incidence of EOCRC (age < 50 years at diagnosis) with unknown causes is rising worldwide, necessitating the mechanistical analysis of its molecular basis. The NOMO1 gene is deleted in a high number of EOCRC tumors compared to LOCRC. In this work, we aimed to test the NOMO1 gene mutational profile in EOCRC tumors and to characterize the effect of NOMO1 loss in different CRISPR/cas9-edited cell lines, as well as in murine models. Here, we show that the NOMO1 gene can be inactivated not only by deletion but also by pathogenic mutations in EOCRC. Our results indicate that NOMO1 loss could be a passenger mutation in the development of EOCRC, although it contributes significantly to colon cancer cell migration.The incidence of early-onset colorectal cancer (EOCRC; age younger than 50 years) has been progressively increasing over the last decades globally, with causes unexplained. A distinct molecular feature of EOCRC is that compared with cases of late-onset colorectal cancer, in EOCRC cases, there is a higher incidence of Nodal Modulator 1 (NOMO1) somatic deletions. However, the mechanisms of NOMO1 in early-onset colorectal carcinogenesis are currently unknown. In this study, we show that in 30% of EOCRCs with heterozygous deletion of NOMO1, there were pathogenic mutations in this gene, suggesting that NOMO1 can be inactivated by deletion or mutation in EOCRC. To study the role of NOMO1 in EOCRC, CRISPR/cas9 technology was employed to generate NOMO1 knockout HCT-116 (EOCRC) and HS-5 (bone marrow) cell lines. NOMO1 loss in these cell lines did not perturb Nodal pathway signaling nor cell proliferation. Expression microarrays, RNA sequencing, and protein expression analysis by LC–IMS/MS showed that NOMO1 inactivation deregulates other signaling pathways independent of the Nodal pathway, such as epithelial–mesenchymal transition and cell migration. Significantly, NOMO1 loss increased the migration capacity of CRC cells. Additionally, a gut-specific conditional NOMO1 KO mouse model revealed no subsequent tumor development in mice. Overall, these findings suggest that NOMO1 could play a secondary role in early-onset colorectal carcinogenesis because its loss increases the migration capacity of CRC cells. Therefore, further study is warranted to explore other signalling pathways deregulated by NOMO1 loss that may play a significant role in the pathogenesis of the disease.

Characterization of Native and Human Serum Albumin-Bound Lysophosphatidic Acid Species and Their Effect on the Viability of Mesenchymal Stem Cells In Vitro

Scaffolds can provide a healthy environment for cell attachment, differentiation, proliferation, and migration in vitro and in vivo. Lysophosphatidic acid (LPA) is a naturally occurring bioactive phospholipid that is present in the serum mainly bound to albumin. The present study aims to investigate the biocompatibility of LPA. It also aims to determine the effect of different LPA species on the proliferation and migration of human bone marrow-derived mesenchymal stem cells (hBM-dMSCs) for LPA and human serum albumin (HSA) containing bone scaffold development. The HSA-LPA complex formation was assessed using Fourier-transform infrared (FTIR) spectroscopy. The effect of 18:1, 18:2, or 16:0 LPA alone, or in combination with 4% HSA, on cell viability and proliferation was determined by XTT. The cell migration was examined in a wound healing assay. The changes in the FTIR spectra of LPA-HSA compositions, compared with HSA alone, indicate the complex formation between the components. Our study showed that 18:1, 18:2, and 16:0 LPA species had no cytotoxic effects up to 10 µM concentration. The different LPA species increased the proliferation of hBM-dMSCs in a dose-dependent manner when administered in the presence of HSA, without an effect on the migration of this cell type. These findings make the in vivo application of LPA-HSA complex promising for bone regeneration.

Biochemical and mechanical regulation of actin dynamics.

Polymerization of actin filaments against membranes produces force for numerous cellular processes, such as migration, morphogenesis, endocytosis, phagocytosis and organelle dynamics. Consequently, aberrant actin cytoskeleton dynamics are linked to various diseases, including cancer, as well as immunological and neurological disorders. Understanding how actin filaments generate forces in cells, how force production is regulated by the interplay between actin-binding proteins and how the actin-regulatory machinery responds to mechanical load are at the heart of many cellular, developmental and pathological processes. During the past few years, our understanding of the mechanisms controlling actin filament assembly and disassembly has evolved substantially. It has also become evident that the activities of key actin-binding proteins are not regulated solely by biochemical signalling pathways, as mechanical regulation is critical for these proteins. Indeed, the architecture and dynamics of the actin cytoskeleton are directly tuned by mechanical load. Here we discuss the general mechanisms by which key actin regulators, often in synergy with each other, control actin filament assembly, disassembly, and monomer recycling. By using an updated view of actin dynamics as a framework, we discuss how the mechanics and geometry of actin networks control actin-binding proteins, and how this translates into force production in endocytosis and mesenchymal cell migration.

Non-tumorigenic epithelial breast cells and ionizing radiation cooperate in the enhancement of mesenchymal traits in tumorigenic breast cancer cells

AimsRadioresistance and recurrences are crucial hindrances in cancer radiotherapy. Fractionated irradiation can elicit a mesenchymal phenotype in irradiated surviving cells and a deep connection exists between epithelial mesenchymal transition, radioresistance, and metastasis. The aim of this study was to analyze the effect of the secretoma of irradiated non-tumorigenic mammary epithelial cells on surviving irradiated breast tumor cells regarding the gain of mesenchymal traits and migratory ability. Main methodsMDA-MB-231 and MCF-7 breast cancer cells, irradiated or not, were incubated with conditioned media from MCF-10A non-tumorigenic epithelial breast cells, irradiated or not. After five days, we evaluated the expression and localization of epithelial and mesenchymal markers (by western blot and indirect immunofluorescence), cell migration (using transwells) and metalloproteinases activity (by zymography). We also assessed TGF-β1 content in conditioned media by immunoblot, and the effect of A83-01 (a selective inhibitor of TGF-β receptor I) and PP2 (a Src-family tyrosine kinase inhibitor) on nuclear Slug and cell migration. Key findingsConditioned media from MCF-10A cells caused phenotypic changes in breast tumor cells with attainment or enhancement of mesenchymal traits mediated at least in part by the activation of the TGF-β type I receptor and a signaling pathway involving Src activation/phosphorylation. The effects were more pronounced mostly in irradiated tumor cells treated with conditioned media from irradiated MCF-10A. SignificanceOur results suggest that non-tumorigenic epithelial mammary cells included in the irradiation field could affect the response to irradiation of post-surgery residual cancer cells enhancing EMT progression and thus modifying radiotherapy efficacy.

Effect of Conditioned Media of Limbal Epithelial Cells and Corneal Stromal Cells on Functional Activity of Limb Mesenchymal Stem Cells

We studied the effect of conditioned media from limbal epithelial stem cells, fibroblasts, and corneal keratocytes on the functional activity of human limbal mesenchymal stem cells. It was shown that the conditioned media from limbal epithelial stem cells reduced proliferative activity and inhibited migration of limbal mesenchymal stem cells. In the conditioned media of limbal epithelial stem cells, increased concentrations of VEGF and TNFα and reduced concentration of BDNF, vimentin, and fibronectin were found. The conditioned medium from corneal stromal cells did not affect functional activity of mesenchymal stem cells in the limbus. These data contribute to the understanding of the interaction of cells in the limbal niche and with corneal cells essential for the maintenance of the cellular homeostasis in the cornea.

TGF-β1-induced bone marrow mesenchymal stem cells (BMSCs) migration via histone demethylase KDM6B mediated inhibition of methylation marker H3K27me3

Mesenchymal stem cells (MSCs) are widely used in clinical research and therapy. Since the number of MSCs migration is extremely crucial at the lesion site, exploring the mechanisms to enhance the migration of MSCs is necessary. Therefore, this study focused on the epigenetic mechanisms in MSCs migration. TGF-β1 stimulated bone marrow mesenchymal stem cells (BMSCs) to promote cell migration at lesion sites in vitro and in vivo. The mRNA and protein levels of several migration-related genes (N cadherin, CXCR4, FN1) were enhanced. The trimethylation marker H3K27me3 recruitment on the promoter of these genes were studied to dissect the epigenetic mechanisms. TGF-β1 elevated the levels of KDM6B leading to removal of repression marker H3K27me3 in the promoter region of N cadherins and FN1. Congruently, knockdown of demethylase KDM6B substantially affected the TGF-β1 induced BMSCs migration. This promoted the down-regulation of various migration-related genes. Collectively, epigenetic regulation played an important role in BMSCs migration, and H3K27me3 was at least partially involved in the migration of BMSCs induced by TGF-β1.

Subchondral bone-inspired hydrogel scaffold for cartilage regeneration

Promoting the in situ regeneration of cartilage without additional cells or cytokines remains challenging. Here, inspired by the unique microstructures of subchondral bone, a cell and cytokine free hydrogel scaffold for cartilage regeneration was developed via a strategy of directional lyophilization and postcrosslinking. This strategy achieved intersecting microchannels in an orderly arrangement and an aligned ladder-like texture in a semi-interpenetrating hydrogel network. The resulting hydrogel had similar mechanical properties to the native cartilage extracellular matrix. Incorporating chitosan into the rigid network also endowed the hydrogel with excellent hemostatic properties. By delicately tuning the components and postcrosslinking conditions, the hydrogel was further endowed with suitable swelling and degradation properties for cartilage regeneration. In vitro tests showed that the highly biocompatible hydrogel scaffold could facilitate the migration and chondrogenic differentiation of bone marrow mesenchymal stem cells. In vivo results further verified that the hydrogel could promote the in situ regeneration of cartilage in a rat model of osteochondral defects. In summary, the subchondral bone-like hydrogel revealed promising prospects in cartilage regeneration and a variety of bioremediation applications.

Physical and Chemical Properties, Biosafety Evaluation, and Effects of Nano Natural Deer Bone Meal on Bone Marrow Mesenchymal Stem Cells.

At present, bone-based products are abundant, and the main sources are bovine bone and pig bone, but there are few studies on the development of deer bone as a bone repair material. Deer bone has important osteogenic effects in the theory of traditional Chinese medicine. It is rich in protein, ossein, and a variety of trace elements, with the effect of strengthening tendons and bones. Nanomaterials and their application in the repair of bone defects have become a research hotspot in bone tissue engineering. In this study, nano-deer bone meal (nBM), nano-calcined deer bone meal, and nano-demineralized bone matrix were successfully prepared. It was found that the Ca/P ratio in deer bone was significantly higher than that in cow bone and human bone tissue, and deer bone contained beneficial trace elements, such as potassium, iron, selenium, and zinc, which were not found in cow bone. The three kinds of deer bone powders prepared in this study had good biocompatibility and met the implantation standards of medical biomaterials. Cell function studies showed that compared with other bone powders, due to the presence of organic active ingredients and inorganic calcium and phosphate salts, nBM had excellent performance in the proliferation, adhesion, migration, and differentiation of bone marrow mesenchymal stem cells. These findings indicate that nBM can be used as a potential osteoinductive active nanomaterial to enhance bone tissue engineering scaffolds with certain application prospects.

Functionalized silk promotes cell migration into calcium phosphate cements by providing macropores and cell adhesion motifs

Calcium phosphate cements (CPCs) are attractive synthetic bone grafts as they possess osteoconductive and osteoinductive properties. Their biomimetic synthesis grants them an intrinsic nano- and microporosity that resembles natural bone and is paramount for biological processes such as protein adhesion, which can later enhance cell adhesion. However, a main limitation of CPCs is the lack of macroporosity, which is crucial to allow cell colonization throughout the scaffold. Moreover, CPCs lack specific motifs to guide cell interactions through their membrane proteins. In this study, we explore a strategy targeting simultaneously both macroporosity and cell binding motifs within CPCs by the use of recombinant silk. A silk protein functionalized with the cell binding motif RGD serves as foaming template of CPCs to achieve biomimetic hydroxyapatite (HA) scaffolds with multiscale porosity. The synergies of RGD-motifs in the silk macroporous template and the biomimetic features of HA are explored for their potential to enhance mesenchymal stem cell adhesion, proliferation, migration and differentiation. Macroporous Silk-HA scaffolds improve initial cell adhesion compared to a macroporous HA in the absence of silk, and importantly, the presence of silk greatly enhances cell migration into the scaffold. Additionally, cell proliferation and osteogenic differentiation are achieved in the scaffolds.

Functions of the bone morphogenetic protein signaling pathway through non-coding RNAs.

Bone morphogenetic proteins (BMPs) are proteins of the transforming growth factor-β (TGF-β) family, which plays an important role in the formation of skeletal and cartilage tissue and their regeneration. BMPs play a key role in the formation of new blood vessels and promote the migration, proliferation, and differentiation of mesenchymal stem cells (MSCs) into chondroblasts and osteoblasts. It is known that malfunction of BMPs signaling can cause a disease state. Epigenetic regulation of expression plays a key role in the control of many cellular processes. Important participants in this regulation are non-coding RNAs (ncRNAs), which are RNA molecules that are not translated into proteins. The best known of these are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). In addition, the results of many studies make it possible to establish an unambiguous functional relationship between these ncRNAs. Being involved in the regulation of a large number of target genes responsible for the life of the cell, miRNAs, lncRNAs, and circRNAs are essential for the normal development and functioning of the body, and the violation of their functions accompanies the development of many pathophysiological processes including oncogenesis. In the present review, we discuss different insights into the regulation of BMPs signaling pathway by miRNAs, lncRNAs and circRNAs governed.

CDK1 Promotes Epithelial-Mesenchymal Transition and Migration of Head and Neck Squamous Carcinoma Cells by Repressing ∆Np63α-Mediated Transcriptional Regulation.

∆Np63α is a key transcription factor overexpressed in types of squamous cell carcinomas (SCCs), which represses epithelial–mesenchymal transition (EMT) and cell migration. In this study, we found that CDK1 phosphorylates ∆Np63α at the T123 site, impairing its affinity to the target promoters of its downstream genes and its regulation of them in turn. Database analysis revealed that CDK1 is overexpressed in head and neck squamous cell carcinomas (HNSCCs), especially the metastatic HNSCCs, and is negatively correlated with overall survival. We further found that CDK1 promotes the EMT and migration of HNSCC cells by inhibiting ∆Np63α. Altogether, our study identified CDK1 as a novel regulator of ΔNp63α, which can modulate EMT and cell migration in HNSCCs. Our findings will help to elucidate the migration mechanism of HNSCC cells.

Mir-29a Promotes the Migration of Bone Marrow Mesenchymal Stem Cells to Oral Squamous Cell Carcinoma Cells

Oral squamous cell carcinoma (OSCC) is a tumor in the oral cavity and around oral mucosa. Mir-29a level was differentially expressed in OSCC patients. However, whether its exact role and function in OSCC remains to be further elucidated. Our study investigated the effect of Mir-29a on the migration of bone marrow mesenchymal stem cells (BMSCs) to oral squamous cell carcinoma cells (OSCCs). Mir-29a level was measured in OSCCs and BMSCs by real-time quantitative PCR and its relationship with Panc-1 was verified by dual luciferase reporter gene. After up-regulation of Mir-29a or treatment with Panc-1 siRNA, BMSCs migration to OSCCs was assessed by transwell assay and Panc-1 and Mir-29a were measure. Mir-29a level was downregualted in OSCCs and Panc-1 was upregulated in BMSCs. Panc-1 and Mir-29a was negatively correlated and Mir-29a could bind and target Panc-1. Down-regulation of Panc-1 inhibited the migration of BMSCs to OSCCs and elevated Mir-29a level promoted cell migration. After co-transfection of Mir-29a inhibitor and Panc-1 siRNA, the inhibited cell migration function can be restored. In conclusion, Mir-29a promotes the migration of BMSCs to OSCCs through targeting Panc-1.