scholarly journals Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Giovanni Giuseppe Giobbe ◽  
Claire Crowley ◽  
Camilla Luni ◽  
Sara Campinoti ◽  
Moustafa Khedr ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Small Intestine ◽  
Cell Growth ◽  
Regenerative Medicine ◽  
Therapeutic Potential ◽  
Organoid Culture ◽  
Transcriptomic Signature ◽  
Compliant Systems ◽  
Opening Up

AbstractOrganoids have extensive therapeutic potential and are increasingly opening up new avenues within regenerative medicine. However, their clinical application is greatly limited by the lack of effective GMP-compliant systems for organoid expansion in culture. Here, we envisage that the use of extracellular matrix (ECM) hydrogels derived from decellularized tissues (DT) can provide an environment capable of directing cell growth. These gels possess the biochemical signature of tissue-specific ECM and have the potential for clinical translation. Gels from decellularized porcine small intestine (SI) mucosa/submucosa enable formation and growth of endoderm-derived human organoids, such as gastric, hepatic, pancreatic, and SI. ECM gels can be used as a tool for direct human organoid derivation, for cell growth with a stable transcriptomic signature, and for in vivo organoid delivery. The development of these ECM-derived hydrogels opens up the potential for human organoids to be used clinically.

scholarly journals A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Soudeh Moghadasi ◽  
Marischa Elveny ◽  
Heshu Sulaiman Rahman ◽  
Wanich Suksatan ◽  
Abduladheem Turki Jalil ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Ethical Issues ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Experimental Models ◽  
Live Cells ◽  
Target Cells ◽  
Intercellular Interaction ◽  
Micro Rnas

AbstractRecently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

scholarly journals Remodeling the Human Adult Stem Cell Niche for Regenerative Medicine Applications

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Silvana Bardelli ◽  
Marco Moccetti
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Translational Medicine ◽  
Process Development ◽  
Therapeutic Potential ◽  
Adult Stem Cell ◽  
Cell Renewal ◽  
Stem Cell Niches

The interactions between stem cells and their surrounding microenvironment are pivotal to determine tissue homeostasis and stem cell renewal or differentiation and regenerationin vivo. Ever since they were postulated in 1978, stem cell niches have been identified and characterized in many germline and adult tissues. Comprehensive studies over the last decades helped to clarify the critical components of stem cell niches that include cellular, extracellular, biochemical, molecular, and physical regulators. This knowledge has direct impact on their inherent regenerative potential. Clinical applications demand readily available cell sources that, under controlled conditions, provide a specific therapeutic function. Thus, translational medicine aims at optimizingin vitroorin vivothe various components and complex architecture of the niche to exploit its therapeutic potential. Accordingly, the objective is to recreate the natural niche microenvironment during cell therapy process development and closely comply with the requests of regulatory authorities. In this paper, we review the most recent advances of translational medicine approaches that target the adult stem cell natural niche microenvironment for regenerative medicine applications.

In vivo Modulation of Human Tumor Cell Growth by Normal Human Extracellular Matrix

Tumor Biology ◽  
1994 ◽  
Vol 15 (6) ◽  
pp. 326-336 ◽  
Author(s):  
Lyndon J. Goodly ◽  
Raj K. Singh ◽  
Ming H. Wang ◽  
Gene P. Siegal
Keyword(s):  
Extracellular Matrix ◽  
Cell Growth ◽  
Tumor Cell ◽  
Human Tumor ◽  
Tumor Cell Growth ◽  
Human Tumor Cell ◽  
Normal Human

scholarly journals Silica-Based Branched Hollow Microfibers as a Biomimetic Extracellular Matrix for Promoting Tumor Cell Growth In Vitro and In Vivo

2013 ◽  
Vol 25 (17) ◽  
pp. 2492-2496 ◽  
Author(s):  
Penghe Qiu ◽  
Xuewei Qu ◽  
Daniel J. Brackett ◽  
Megan R. Lerner ◽  
Dong Li ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cell Growth

scholarly journals Preclinical Validation of Ubiquitin Receptor PSMD4 As Therapeutic Target in Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4403-4403
Author(s):  
Yan Song ◽  
Ting DU ◽  
Arghya Ray ◽  
Dharminder Chauhan ◽  
Kenneth C. Anderson
Keyword(s):  
Multiple Myeloma ◽  
Cell Growth ◽  
Cell Line ◽  
Therapeutic Potential ◽  
Statistical Significance ◽  
Annexin V ◽  
Endoplasmic Reticulum Stress Response ◽  
In Vivo Models

Background and Rationale Our preclinical studies have focused on Identification and validation of components within the ubiquitin proteasome system which can be targeted with novel therapies to overcome proteasome-inhibitor (PI)-resistance in multiple myeloma (MM). Our siRNA screening studies identified ubiquitin Receptor (UbR) PSMD4/Rpn10 as a mediator of MM cell growth and survival. Rpn10 is localized on the 19S regulatory lid of the proteasome, and plays a key role in chaperoning ubiquitinated substrate proteins for downstream 20S proteasomal degradation. Here, we show that inhibition of Rpn10 triggers potent anti-MM activity using both in in vitro and in vivo models of MM, including against PI-resistant MM cells. Materials and Methods Rpn10 knockout 293 cell line was generated using CRISPR/Cas9. Rpn10-inducible knockdown (KD) MM.1S cell line was generated using shRNA. Drug sensitivity, cell viability, and apoptosis assays were performed using WST/CellTiter-Glo assay, and Annexin V staining, respectively. Cell signaling and caspase activity were determined by western blotting. Proteasome activity was measured as previously described (Chauhan et al., Cancer Cell 2012, 22:345-358). A xenograft human MM model was used to characterize the role of Rpn10 on tumor progression. Statistical significance was assessed with Student's t test. Results 1) Analysis of MM patient gene expression profiling database showed that Rpn10 expression inversely correlates with overall survival (n=175; p= 0.00064). 2)Real-time PCR, immunoblotting, and immunohistochemistry of MM patient bone marrow showed higher Rpn10 levels in patient MM cells and MM cell lines versus normal cells. 3)Transient transfection of MM cells with Rpn10-siRNA decreased their viability; conversely, transfection with Rpn10-WT specifically rescued cells from growth-inhibitory activity of Rpn10-siRNA. Immunoblot analysis confirmed significant knockdown of Rpn10 by Rpn10-siRNA versus scrambled (scr)-siRNA, and restoration of Rpn10 levels in cells transfected with Rpn10-WT versus Rpn10-siRNA. 4)Genetic blockade of Rpn10 decreased viability in bortezomib-resistant MM cells. 5)CRISPR/Cas9-mediated knockout (KO) of Rpn10 decreased cell growth. 5)Both Rpn10-KO and inducible Rpn10-KD cells showed elevated levels of polyubiquitylated proteins. 6)Inhibition of Rpn10 induced apoptosis, cell-cycle arrest, activation of caspases, and endoplasmic reticulum stress response signaling. 7)Reduced tumor growth was noted in mice xenografted with Rpn10-KD MM.1S cells versus mice engrafted with WT-MM.1S cells. Conclusion Our data demonstrate the therapeutic potential of targeting ubiquitin receptor Rpn10/PSMD4, and provide the preclinical basis for development of Rpn10 inhibitors to overcome PI-resistance in MM. Disclosures Chauhan: C4 Therapeutics.: Equity Ownership; Stemline Therapeutics: Consultancy. Anderson:Sanofi-Aventis: Other: Advisory Board; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Other: Scientific Founder; Oncopep: Other: Scientific Founder; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.

Extracellular Matrix Covered Biomaterials for Human Endothelial Cell Growth

1992 ◽  
Vol 15 (12) ◽  
pp. 722-726 ◽  
Author(s):  
P. Desgranges ◽  
M. Tardieu ◽  
D. Loisance ◽  
D. Barritault
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Percoll Gradient ◽  
Human Endothelial Cells ◽  
Endothelial Cell Growth ◽  
Class Ii Antigens

The aim of this study is to optimize conditions for growing endothelial cells on vascular biomaterials. Bovine cornea endothelial cells (BCEC), stimulated by basic Fibroblast Growth Factor (bFGF) secrete an extracellular matrix (ECM) similar to the Descemet membrane produced in vivo by these cells. This ECM, obtained by removing BCEC with an hypotonic shock can be used as a substratum for other endothelial cell growth. Human endothelial cells (HEC) were purified from omentum that was digested with a solution of collagenase-dispase, then filtered through nylon meshes. The cells were further purified by centrifugation onto a Percoll gradient. A comparative study on the attachment and growth of HEC on various coatings (laminin, poly-L-lysine, fibronectin or ECM) indicates that ECM is the most performing substratum. The quality of this endothelium was confirmed by the presence of factor VIII, and MHC class I and the absence of class II antigens.

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Potential

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ashley G. Zhao ◽  
Kiran Shah ◽  
Brett Cromer ◽  
Huseyin Sumer
Keyword(s):  
Tissue Engineering ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Multipotent Cells ◽  
Membrane Bound

Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles, which act as shuttles, delivering a range of biomolecules to diverse target cells. They play an important role in maintenance of biophysiological homeostasis and cellular, physiological, and pathological processes. EVs have significant diagnostic and therapeutic potentials and have been studied both in vitro and in vivo in many fields. Mesenchymal stem cells (MSCs) are multipotent cells with many therapeutic applications and have also gained much attention as prolific producers of EVs. MSC-derived EVs are being explored as a therapeutic alternative to MSCs since they may have similar therapeutic effects but are cell-free. They have applications in regenerative medicine and tissue engineering and, most importantly, confer several advantages over cells such as lower immunogenicity, capacity to cross biological barriers, and less safety concerns. In this review, we introduce the biogenesis of EVs, including exosomes and microvesicles. We then turn more specifically to investigations of MSC-derived EVs. We highlight the great therapeutic potential of MSC-derived EVs and applications in regenerative medicine and tissue engineering.

Therapeutic potential of microRNA in tendon injuries

2020 ◽  
Vol 133 (1) ◽  
pp. 79-94 ◽  
Author(s):  
Lorenzo Giordano ◽  
Giovanna Della Porta ◽  
Giuseppe M Peretti ◽  
Nicola Maffulli
Keyword(s):  
Extracellular Matrix ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Tendon Healing ◽  
Tendon Injuries ◽  
In Vivo Studies ◽  
Proliferation And Differentiation ◽  
Effective Delivery ◽  
Clinical Potential

Abstract Introduction The regulatory role of microRNA (miRNA) in several conditions has been studied, but their function in tendon healing remains elusive. This review summarizes how miRNAs are related to the pathogenesis of tendon injuries and highlights their clinical potential, focusing on the issues related to their delivery for clinical purposes. Sources of data We searched multiple databases to perform a systematic review on miRNA in relation to tendon injuries. We included in the present work a total of 15 articles. Areas of agreement The mechanism of repair of tendon injuries is probably mediated by resident tenocytes. These maintain a fine equilibrium between anabolic and catabolic events of the extracellular matrix. Specific miRNAs regulate cytokine expression and orchestrate proliferation and differentiation of stromal cell lines involved in the composition of the extracellular matrix. Areas of controversy The lack of effective delivery systems poses serious obstacles to the clinical translation of these basic science findings. Growing point In vivo studies should be planned to better explore the relationship between miRNA and tendon injuries and evaluate the most suitable delivery system for these molecules. Areas timely for developing research Investigations ex vivo suggest therapeutic opportunities of miRNA for the management of tendon injuries. Given the poor pharmacokinetic properties of miRNAs, these must be delivered by an adequate adjuvant transport system.

scholarly journals Integration of Epigallocatechin Gallate in Gelatin Sponges Attenuates Matrix Metalloproteinase-Dependent Degradation and Increases Bone Formation

2019 ◽  
Vol 20 (23) ◽  
pp. 6042 ◽  
Author(s):  
Anqi Huang ◽  
Yoshitomo Honda ◽  
Peiqi Li ◽  
Tomonari Tanaka ◽  
Shunsuke Baba
Keyword(s):  
Computed Tomography ◽  
Extracellular Matrix ◽  
Regenerative Medicine ◽  
Bone Formation ◽  
Matrix Metalloproteinase ◽  
Epigallocatechin Gallate ◽  
Bone Defects ◽  
Micro Computed Tomography ◽  
Immunohistological Staining

Matrix metalloproteinase (MMP)-2 and MMP-9 are well-known gelatinases that disrupt the extracellular matrix, including gelatin. However, the advantages of modulating MMP expression in gelatin-based materials for applications in bone regenerative medicine have not been fully clarified. In this study, we examined the effects of epigallocatechin gallate (EGCG), a major polyphenol catechin isolated from green tea, on MMP expression in gelatin sponges and its association with bone formation. Four gelatin sponges with or without EGCG were prepared and implanted into bone defects for up to 4 weeks. Histological and immunohistological staining were performed. Micro-computed tomography was used to estimate the bone-forming capacity of each sponge. Our results showed that EGCG integration attenuated MMP-2 (70.6%) and -9 expression (69.1%) in the 1 week group, increased residual gelatin (118.7%), and augmented bone formation (101.8%) in the 4 weeks group in critical-sized bone defects of rat calvaria compared with vacuum-heated gelatin sponges without EGCG. Moreover, vacuum-heated gelatin sponges with EGCG showed superior bone formation compared with other sponges. The results indicated that integration of EGCG in gelatin-based materials modulated the production and activity of MMP-2 and -9 in vivo, thereby enhancing bone-forming capacity.

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