Potential Use In Regenerative Medicine Research Articles

Decellularized Extracellular Matrix: The Role of This Complex Biomaterial in Regeneration.

Organ transplantation is understood as a technique where an organ from a donor patient is transferred to a recipient patient. This practice gained strength in the 20th century and ensured advances in areas of knowledge such as immunology and tissue engineering. The main problems that comprise the practice of transplants involve the demand for viable organs and immunological aspects related to organ rejection. In this review, we address advances in tissue engineering for reversing the current challenges of transplants, focusing on the possible use of decellularized tissues in tissue engineering. We address the interaction of acellular tissues with immune cells, especially macrophages and stem cells, due to their potential use in regenerative medicine. Our goal is to exhibit data that demonstrate the use of decellularized tissues as alternative biomaterials that can be applied clinically as partial or complete organ substitutes.

Differentiation of Human Induced Pluripotent Stem Cells (iPSCs)-derived Mesenchymal Progenitors into Chondrocytes.

Induced pluripotent stem cells (iPSCs) generated from human sources are valuable tools for studying skeletal development and diseases, as well as for potential use in regenerative medicine for skeletal tissues such as articular cartilage. To successfully differentiate human iPSCs into functional chondrocytes, it is essential to establish efficient and reproducible strategies that closely mimic the physiological chondrogenic differentiation process. Here, we describe a simple and efficient protocol for differentiation of human iPSCs into chondrocytes via generation of an intermediate population of mesenchymal progenitors. These methodologies include step-by-step procedures for mesenchymal derivation, induction of chondrogenic differentiation, and evaluation of the chondrogenic marker gene expression. In this protocol, we describe the detailed procedure for successful derivation of mesenchymal progenitor population from human iPSCs, which are then differentiated into chondrocytes using high-density culture conditions by stimulating with bone morphogenetic protein-2 (BMP-2) or transforming growth factor beta-3 (TGFβ-3). The differentiated iPSCs exhibit temporal expression of cartilage genes and accumulation of a cartilaginous extracellular matrix in vitro, indicating successful chondrogenic differentiation. These detailed methodologies help effective differentiation of human iPSCs into the chondrogenic lineage to obtain functional chondrocytes, which hold great promise for modeling skeletal development and disease, as well as for potential use in regenerative medicine for cell-based therapy for cartilage regeneration. Key features • Differentiation of human iPSCs into chondrocytes using 3D culture methods. • Uses mesenchymal progenitors as an intermediate for differentiation into chondrocytes.

Engineered adult stem cells: Current clinical trials status of disease treatment.

Regenerative medicine is an interdisciplinary field involving the process of replacing and regenerating cells/tissues or organs by integrating medicine, science, and engineering principles to enhance the intrinsic regenerative capacity of the host. Recently, engineered adult stem cells have gained attention for their potential use in regenerative medicine by reducing inflammation and modulating the immune system. This chapter introduces adult stem cell engineering and chimeric antigen receptor T cells (CAR T) gene therapy and summarises current engineered stem cell- and extracellular vesicles (EVs)-focused clinical trial studies that provide the basis for the proposal of a personalised medicine approach to diseases diagnosis and treatment.

Structural, Spectroscopic, and Biological Characterization of Novel Rubidium(I) and Europium(III) Co-Doped Nano-Hydroxyapatite Materials and Their Potential Use in Regenerative Medicine.

This research investigates hydrothermally synthesized hydroxyapatite nanoparticles doped with rubidium(I) and europium(III) ions. Investigation focused on establishing the influence of co-doped Eu3+ and Rb+ ions on hydroxyapatite lattice. Therefore, structural, and morphological properties were characterized via using X-ray powder diffraction (XRPD), infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), as well as transmission electron microscopy (TEM) techniques. Furthermore, this investigation evaluates the impact of various Rb+ ion doping concentrations on the distinct red emission of co-doped Eu3+ ions. Hence, luminescence properties of the obtained materials were evaluated by measuring emission excitation, emission spectra, and luminescence decays. As established by numerous studies, synthetic hydroxyapatite has excellent application in biomedical field, as it is fully biocompatible. Its biocompatible makes it highly useful in the biomedical field as a bone fracture filler or hydroxyapatite coated dental implant. By the incorporation of Eu3+ ions and Rb+ ions we established the impact these co-doped ions have on the biocompatibility of hydroxyapatite powders. Therefore, biocompatibility toward a ram's red blood cells was evaluated to exclude potential cytotoxic features of the synthesized compounds. Additionally, experimental in vitro bioactive properties of hydroxyapatite nanoparticles doped with Rb+ and Eu3+ ions were established using a mouse osteoblast model. These properties are discussed in detail as they contribute to a novel method in regenerative medicine.

Clinical Approach of Novel Autologous Stem Cell Therapy for Primary Ovarian Insufficiency and Endometrial Regeneration

Bone Marrow-Derived Mesenchymal Stem Cell Fraction (BMSCF) therapy has various applications as potential use in regenerative medicine. Here, we present an original case of Primary ovarian insufficiency associated with poor ovarian reserves and thin endometrium in a woman who achieved a live birth with BMSCF supplemented with PRP (platelet rich plasma). The age between 24 to 42-year-old woman (n=10) came to our centre with primary infertility. Her husband's sperm count and quality was normal

Structural, Spectroscopic and Biological Characterization of Novel Rubidium(I) and Europium (Iii) Co-Doped Nano-Hydroxyapatite Materials and Their Potential Use in Regenerative Medicine

Structural, Spectroscopic and Biological Characterization of Novel Rubidium(I) and Europium (Iii) Co-Doped Nano-Hydroxyapatite Materials and Their Potential Use in Regenerative Medicine

Potential Biomedical Applications of Collagen Filaments derived from the Marine Demosponges Ircinia oros (Schmidt, 1864) and Sarcotragus foetidus (Schmidt, 1862)

Collagen filaments derived from the two marine demosponges Ircinia oros and Sarcotragus foetidus were for the first time isolated, biochemically characterised and tested for their potential use in regenerative medicine. SDS-PAGE of isolated filaments revealed a main collagen subunit band of 130 kDa in both of the samples under study. DSC analysis on 2D membranes produced with collagenous sponge filaments showed higher thermal stability than commercial mammalian-derived collagen membranes. Dynamic mechanical and thermal analysis attested that the membranes obtained from filaments of S. foetidus were more resistant and stable at the rising temperature, compared to the ones derived from filaments of I. oros. Moreover, the former has higher stability in saline and in collagenase solutions and evident antioxidant activity. Conversely, their water binding capacity results were lower than that of membranes obtained from I. oros. Adhesion and proliferation tests using L929 fibroblasts and HaCaT keratinocytes resulted in a remarkable biocompatibility of both developed membrane models, and gene expression analysis showed an evident up-regulation of ECM-related genes. Finally, membranes from I. oros significantly increased type I collagen gene expression and its release in the culture medium. The findings here reported strongly suggest the biotechnological potential of these collagenous structures of poriferan origin as scaffolds for wound healing.

Development of Biodegradable Polymer Blends Based on Chitosan and Polylactide and Study of Their Properties.

Composite materials of various compositions based on chitosan and polylactide were obtained in the form of films or porous bulk samples. Preliminarily, poly-d,l-lactide was synthesized by ring-opening polymerization of lactide in the presence of Ti(OiPr)4. Polylactide obtained at components molar ratio [lactide]:[Ti(OiPr)4] = 3:1 had the best molecular weight characteristics at a high product yield. Film composition with the weight ratio chitosan-polylactide 50:50 wt. % was characterized by high mechanical properties. The value of the tensile strength of the film was 72 MPa with a deformation of 10% and an elastic modulus of 40 GPa, which is higher than the tensile strength of native chitosan by ~three times. The observed effect is a consequence of the fact that the chitosan-polylactide composite has an amorphous structure in contrast to the native chitosan, which is proved by X-ray phase analysis. An increase in the elastic modulus of the composite in the range of 20–60 °C in contrast to polylactide was found by dynamic mechanical analysis. The observed effect is apparently caused by the formation of hydrogen bonds between functional groups of chitosan and polylactide which is possible through an increase in polylactide segments mobility when its glass transition temperature is reached. The composite material is biocompatible and characterized by high cellular adhesion of fibroblasts (line hTERT BJ-5ta). Their growth on the composite surface was 2.4 times more active than on native chitosan. Bulk porous samples of the composition with the weight ratio chitosan-polylactide 50:50 wt. % were synthesized by original method in ammonium bicarbonate presence. Samples were characterized by a porosity of 82.4% and an average pore size of 100 microns. The biodegradability of such material and absence of inflammatory processes were proven in vivo by the blood parameters of experimental animals. Thus, materials with the weight ratio chitosan-polylactide 50:50 wt. % are promising for potential use in regenerative medicine.

Dynamic mechanical analysis of agarose-based biopolymers with potential use in regenerative medicine

Regenerative medicine is used for tissue healing, replace missing organs and tissues which are affected by aging, disease, or trauma both structurally and functionally. Materials are the key component of regenerative medicine approaches because the material can imitate the native extracellular matrix of those tissues and improve both the physical behavior and the properties of new tissue. However, most of the available materials used for that purpose fail to provide adequate mechanical properties to replicate the behavior of the original tissue. Thus, most of these applications are still far from being enduring. This project aims to determine the multi-scale mechanical properties of some biopolymers with potential use in regenerative medicine. In this very first part, Dynamic Mechanical Analysis (DMA) was performed using shear mode on different type VII agarose-based biopolymers at room temperature during 10 min cycles at 1 Hz frequency. On one hand, samples of fibrine-agarose were tested, and on the other, different compositions of chitosan-agarose, while pure type VII agarose was used as control. Computed values for the storage and loss modulus and the small values for Tan delta ratio (tan δ) show that all materials become elastic, and they have a good capacity to dissipate energy per cycle of deformation. This fact means that all materials are suitable for being used as a scaffold for cell culture, a possible material for bioprinting applications and they could have potential use in regenerative medicine.

Influence of Hypothermic Storage Fluids on Mesenchymal Stem Cell Stability: A Comprehensive Review and Personal Experience.

Mesenchymal stem cells have generated a great deal of interest due to their potential use in regenerative medicine and tissue engineering. Examples illustrating their therapeutic value across various in vivo models are demonstrated in the literature. However, some clinical trials have not proved their therapeutic efficacy, showing that translation into clinical practice is considerably more difficult and discrepancies in clinical protocols can be a source of failure. Among the critical factors which play an important role in MSCs’ therapeutic efficiency are the method of preservation of the stem cell viability and various characteristics during their storage and transportation from the GMP production facility to the patient’s bedside. The cell storage medium should be considered a key factor stabilizing the environment and greatly influencing cell viability and potency and therefore the effectiveness of advanced therapy medicinal product (ATMP) based on MSCs. In this review, we summarize data from 826 publications concerning the effect of the most frequently used cell preservation solutions on MSC potential as cell-based therapeutic medicinal products.

Unravelling Heterogeneity of Amplified Human Amniotic Fluid Stem Cells Sub-Populations.

Human amniotic fluid stem cells (hAFSCs) are broadly multipotent immature progenitor cells with high self-renewal and no tumorigenic properties. These cells, even amplified, present very variable morphology, density, intracellular composition and stemness potential, and this heterogeneity can hinder their characterization and potential use in regenerative medicine. Celector® (Stem Sel ltd.) is a new technology that exploits the Non-Equilibrium Earth Gravity Assisted Field Flow Fractionation principles to characterize and label-free sort stem cells based on their solely physical characteristics without any manipulation. Viable cells are collected and used for further studies or direct applications. In order to understand the intrapopulation heterogeneity, various fractions of hAFSCs were isolated using the Celector® profile and live imaging feature. The gene expression profile of each fraction was analysed using whole-transcriptome sequencing (RNAseq). Gene Set Enrichment Analysis identified significant differential expression in pathways related to Stemness, DNA repair, E2F targets, G2M checkpoint, hypoxia, EM transition, mTORC1 signalling, Unfold Protein Response and p53 signalling. These differences were validated by RT-PCR, immunofluorescence and differentiation assays. Interestingly, the different fractions showed distinct and unique stemness properties. These results suggest the existence of deep intra-population differences that can influence the stemness profile of hAFSCs. This study represents a proof-of-concept of the importance of selecting certain cellular fractions with the highest potential to use in regenerative medicine.

Transcriptome Analysis Reveals High Similarities between Adult Human Cardiac Stem Cells and Neural Crest-Derived Stem Cells.

Simple SummaryThe regeneration of nearly all organs of the human body mainly depends on the functionality of adult stem cell populations that reside in their respective niches and can be activated upon injuries or other damages. These stem cell populations greatly differ in their expression profile of molecular markers, which greatly influences their potential use in regenerative medicine. Neural crest-derived stem cells are a prominent subpopulation of adult stem cells and are known for their high regenerative potential. Within this study, we compared two adult human stem cell populations, namely neural crest-derived inferior turbinate stem cells from the nasal cavity and human cardiac stem cells from the heart, using global gene expression profiling. Here, we found differences that correspond to the tissue sources of origin but also similarities in the expression of markers that are associated with the neural crest. Further classifying nasal stem cells and cardiac stem cells in a broader context, we identified clear similarities between both populations and other adherent stem cell populations compared to non-adherent progenitor cells of the blood system. The analyses provided here might help to understand the differences and similarities between different adult human stem cell populations.For the identification of a stem cell population, the comparison of transcriptome data enables the simultaneous analysis of tens of thousands of molecular markers and thus enables the precise distinction of even closely related populations. Here, we utilized global gene expression profiling to compare two adult human stem cell populations, namely neural crest-derived inferior turbinate stem cells (ITSCs) of the nasal cavity and human cardiac stem cells (hCSCs) from the heart auricle. We detected high similarities between the transcriptomes of both stem cell populations, particularly including a range of neural crest-associated genes. However, global gene expression likewise reflected differences between the stem cell populations with regard to their niches of origin. In a broader analysis, we further identified clear similarities between ITSCs, hCSCs and other adherent stem cell populations compared to non-adherent hematopoietic progenitor cells. In summary, our observations reveal high similarities between adult human cardiac stem cells and neural crest-derived stem cells from the nasal cavity, which include a shared relation to the neural crest. The analyses provided here may help to understand underlying molecular regulators determining differences between adult human stem cell populations.

Conjugates of Chitosan and Calcium Alginate with Oligoproline and Oligohydroxyproline Derivatives for Potential Use in Regenerative Medicine

New materials that are as similar as possible in terms of structure and biology to the extracellular matrix (external environment) of cells are of great interest for regenerative medicine. Oligoproline and oligohydroxyproline derivatives (peptides 2–5) are potential mimetics of collagen fragments. Peptides 2–5 have been shown to be similar to the model collagen fragment (H-Gly-Hyp-Pro-Ala-Hyp-Pro-OH, 1) in terms of both their spatial structure and biological activity. In this study, peptides 2–5 were covalently bound to nonwovens based on chitosan and calcium alginate. Incorporation of the peptides was confirmed by Fourier transform -infrared (FT-IR) and zeta potential measurements. Biological studies (cell metabolic activity by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and Live/Dead assay) proved that the obtained peptide-polysaccharide conjugates were not toxic to the endothelial cell line EA.hy 926. In many cases, the conjugates had a highly affirmative influence on cell proliferation. The results of this study show that conjugates of chitosan and calcium alginate with oligoproline and oligohydroxyproline derivatives have potential for use in regenerative medicine.

Development of 3D Hepatic Constructs Within Polysaccharide-Based Scaffolds with Tunable Properties.

Organoids production is a key tool for in vitro studies of physiopathological conditions, drug-induced toxicity assays, and for a potential use in regenerative medicine. Hence, it prompted studies on hepatic organoids and liver regeneration. Numerous attempts to produce hepatic constructs had often limited success due to a lack of viability or functionality. Moreover, most products could not be translated for clinical studies. The aim of this study was to develop functional and viable hepatic constructs using a 3D porous scaffold with an adjustable structure, devoid of any animal component, that could also be used as an in vivo implantable system. We used a combination of pharmaceutical grade pullulan and dextran with different porogen formulations to form crosslinked scaffolds with macroporosity ranging from 30 µm to several hundreds of microns. Polysaccharide scaffolds were easy to prepare and to handle, and allowed confocal observations thanks to their transparency. A simple seeding method allowed a rapid impregnation of the scaffolds with HepG2 cells and a homogeneous cell distribution within the scaffolds. Cells were viable over seven days and form spheroids of various geometries and sizes. Cells in 3D express hepatic markers albumin, HNF4α and CYP3A4, start to polarize and were sensitive to acetaminophen in a concentration-dependant manner. Therefore, this study depicts a proof of concept for organoid production in 3D scaffolds that could be prepared under GMP conditions for reliable drug-induced toxicity studies and for liver tissue engineering.

Importance of Stem Cell Migration and Angiogenesis Study for Regenerative Cell-based Therapy: A Review.

Stem cells play an essential role in maintaining homeostasis, as well as participating in new tissue regeneration. Over the past 20 years, a great deal of effort has been made to investigate the behaviour of stem cells to enable their potential use in regenerative medicine. However, a variety of biological characteristics are known to exist among the different types of stem cells due to variations in the methodological approach, formulation of cell culture medium, isolation protocol and cellular niches, as well as species variation. In recent years, cell-based therapy has emerged as one of the advanced techniques applied in both medical and clinical settings. Cell therapies aim to treat and repair the injury sites and replace the loss of tissues by stimulating the repair and regeneration process. In order to enable the use of stem cells in regenerative therapies, further characterisation of cell behaviour, in terms of their proliferation and differentiation capacity, mainly during the quiescent and inductive state is regarded as highly necessary. The central focus of regenerative medicine revolves around the use of human cells, including adult stem cells and induced pluripotent stem cells for cell-based therapy. The purpose of this review was to examine the existing body of literature on stem cell research conducted on cellular angiogenesis and migration, to investigate the validity of different strategies and variations of the cell type used. The information gathered within this review may then be shared with fellow researchers to assist in future research work, engaging in stem cell homing for cell-based therapy to enhance wound healing and tissue regeneration process.

Conjugates of Copper Alginate with Arginine-Glycine-Aspartic Acid (RGD) for Potential Use in Regenerative Medicine.

Current restrictions on the use of antibiotics, associated with increases in bacterial resistance, require new solutions, including materials with antibacterial properties. In this study, copper alginate fibers obtained using the classic wet method were used to make nonwovens which were modified with arginine-glycine-aspartic acid (RGD) derivatives. Stable polysaccharide-peptide conjugates formed by coupling with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TosO−), and materials with physically embedded RGD derivatives, were obtained. The materials were found to be characterized by very high antibacterial activity against S. aureus and K. pneumoniae. Cytotoxicity studies confirmed that the materials are not cytotoxic. Copper alginate conjugates with RGD peptides have strong potential for use in regenerative medicine, due to their biocompatibility and innate antibacterial activity.

Stability characteristic of cryopreserved human umbilical cord wharton's jelly–derived mesenchymal stromal cells

Background & Aim Mesenchymal stromal cells (MSCs) are multipotent mesodermal linage derived stem cells that can self–replicate and differentiate into all mesodermal, some of neuroectodermal and hepatic endodermal progenies. Umbilical cord derived Wharton's jelly MSCs (WJ–MSCs) are an attractive source for cell–based therapy regenerative medicine due to the stability in large scale expansion, non–tumor formation and low immunological rejection. Therefore, WJ–MSCs are a superior banking MSCs source for further clinical application. Methods, Results & Conclusion WJ–MSCs were isolated at a 100% successful rate and characterized by flow cytometry for CD34, CD45, CD73, CD90, CD105, CD106 and STRO–1. Growth kinetics characteristics were investigated by population doublings (PD), clinical large–scale expansion and high viability maintenance. MSCs were assessed for differentiation potential to cartilage, adipose and bone. Flow cytometry analysis showed no differences in expression of CD34, CD45, CD73, CD90, CD105, CD106 and STRO–1 among all cryopreserved WJ–MSCs for six years (2013–2018: n=30). All years of cryopreserved WJ–MSCs maintained high proliferative potential with no difference in all passages. Moreover, they were capable to differentiate into cartilage, adipose and bone structures as determined with histochemistry. WJ–MSCs have a high potential for stem cell banking from umbilical cord due to its noninvasive techniques of procurement, high successful isolation rate and low risk microorganism contamination. Furthermore, WJ–MSCs are suitable sources of stem cells for potential use in regenerative medicine in further clinical applications. Mesenchymal stromal cells (MSCs) are multipotent mesodermal linage derived stem cells that can self–replicate and differentiate into all mesodermal, some of neuroectodermal and hepatic endodermal progenies. Umbilical cord derived Wharton's jelly MSCs (WJ–MSCs) are an attractive source for cell–based therapy regenerative medicine due to the stability in large scale expansion, non–tumor formation and low immunological rejection. Therefore, WJ–MSCs are a superior banking MSCs source for further clinical application. WJ–MSCs were isolated at a 100% successful rate and characterized by flow cytometry for CD34, CD45, CD73, CD90, CD105, CD106 and STRO–1. Growth kinetics characteristics were investigated by population doublings (PD), clinical large–scale expansion and high viability maintenance. MSCs were assessed for differentiation potential to cartilage, adipose and bone. Flow cytometry analysis showed no differences in expression of CD34, CD45, CD73, CD90, CD105, CD106 and STRO–1 among all cryopreserved WJ–MSCs for six years (2013–2018: n=30). All years of cryopreserved WJ–MSCs maintained high proliferative potential with no difference in all passages. Moreover, they were capable to differentiate into cartilage, adipose and bone structures as determined with histochemistry. WJ–MSCs have a high potential for stem cell banking from umbilical cord due to its noninvasive techniques of procurement, high successful isolation rate and low risk microorganism contamination. Furthermore, WJ–MSCs are suitable sources of stem cells for potential use in regenerative medicine in further clinical applications.

Semi self-doped electroconductive and biocompatible polyaniline/sulfonated β-cyclodextrin (PANI/SCD) inclusion complex with potential use in regenerative medicine

The aim of this study was to synthesize and characterize a semi self-doped polyaniline/sulfonated β-cyclodextrin (PANI/SCD) inclusion complex with an optimum electroconductivity and a maximized biocompatibility. In this work, β-cyclodextrin (CD) was sulfonated in which sulfonic acid group on the prepared SCD act as the dopant group. PANI/SCD inclusion complex was synthesized using interfacial oxidative polymerization of aniline in presence of SCD and was characterized by elemental analysis, 1H-NMR, FT-IR, XRD, SEM and EIS analyses. The electrical conductivity of the PANI/SCD inclusion complex was found about 2.23 µS⋅cm−1 in dedoped form and was almost equal to each of HCl doped PANI. Cytotoxicity of the PANI, PANI/CD, and PANI/SCD were studied both in HCl doped and dedoped forms using bone marrow-derived rabbit mesenchymal stem cells (rbMSCs) in compliance with ISO standard. Simultaneous effect of different parameters on cell biocompatibility of the synthesized materials investigated using two-way ANOVA and Tukey’s multiple comparison tests. Despite the fact that the PANI/SCD was found to be more cytotoxic than the PANI/CD, but due to its higher electrical conductivity, it can be considered as a material with optimum electroconductivity-biocompatibility balance and a potential use in tissue engineering and/or regenerative medicine as an electroactive scaffold.

On the design and efficacy assessment of self-assembling peptide-based hydrogel-glycosaminoglycan mixtures for potential repair of early stage cartilage degeneration.

Peptide-based hydrogels are of interest for their potential use in regenerative medicine. Combining these hydrogels with materials that may enhance their physical and biological properties, such as glycosaminoglycans, has the potential to extend their range of biomedical applications, for example in the repair of early cartilage degeneration. The aim of this study was to combine three self-assembling peptides (P11 -4, P11 -8, and P11 -12) with chondroitin sulphate at two molar ratios of 1:16 and 1:64 in 130 and 230mM Na+ salt concentrations. The study investigates the effects of mixing self-assembling peptide and glycosaminoglycan on the physical and mechanical properties at 37°C. Peptide alone, chondroitin sulphate alone, and peptide in combination with chondroitin sulphate were analysed using Fourier transform infrared spectroscopy to determine the β-sheet percentage, transmission electron microscopy to determine the fibril morphology, and rheology to determine the elastic and viscous modulus of the materials. All of the variables (peptide, salt concentration, and chondroitin sulphate molar ratio) had an effect on the mechanical properties, β-sheet formation, and fibril morphology of the hydrogels. P11 -4 and P11 -8-chondroitin sulphate mixtures, at both molar ratios, were shown to have a high β-sheet percentage, dense entangled fibrillar networks, as well as high mechanical stiffness in both (130 and 230mM) Na+ salt solutions when compared with the P11 -12/chondroitin sulphate mixtures. These peptide/chondroitin sulphate hydrogels show promise for biomedical applications in glycosaminoglycan depleted tissues.

Human Bone Marrow Mesenchymal Stem Cells Promote Gastric Cancer Growth via Regulating c-Myc.

The clinical application of human bone marrow mesenchymal stem cells (hBM-MSCs) has generated a great deal of interest because of their potential use in regenerative medicine and tissue engineering. However, safety concerns over hBM-MSCs limit their clinical application. In this study, we observed that hBM-MSC-conditioned medium (hBM-MSC-CM) promotes gastric cancer development via upregulation of c-Myc. Our results showed that c-Myc was upregulated in MGC-803 and BGC-823 cells after hBM-MSC-CM treatment. Moreover, we found that the c-Myc inhibitor JQ1 and c-Myc siRNA decreased the expression of c-Myc in hBM-MSC-CM-treated tumor cells in vitro. Additionally, hBM-MSC-CM enhanced the migration and glucose uptake of gastric cancer cells. In vivo studies showed that JQ1 inhibited hBM-MSC-CM-induced gastric cancer growth. These results indicated that hBM-MSC-CM induced gastric cancer growth via upregulation of c-Myc, which may be a potential risk factor and/or a therapeutic target for clinical applications.