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Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration

Bioactive Materials 2021年第10期6卷 3541-3556页

作者： Yizhong Peng Xiangcheng Qing Hui Lin Donghua Huang Jinye Li Shuo Tian Sheng Liu Xiao Lv Kaige Ma Rui Li Zilong Rao Ying Bai Songfeng Chen Ming Lei Daping Quan Zengwu Shao Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Musculoskeletal Tumor Center Department of OrthopedicsThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina School of Chemistry Sun Yat-sen UniversityGuangzhou510127China School of Materials Science and engineering Sun Yat-sen UniversityGuangzhou510127China Department of Orthopaedic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou City450052China

tissue specificity,a key factor in the decellularized tissue matrix(DTM),has shown bioactive functionalities in tuning cell fate-e.g.,the differentiation of mesenchymal stem ***,cell fate is also determined by the living microenvironment,including material composition and spatial ***,two neighboring tissues within intervertebral discs,the nucleus pulposus(NP)and annulus fibrosus(AF),were carefully processed into DTM hydrogels(abbreviated DNP-G and DAF-G,respectively)to determine the tissue-specific effects on stem cell fate,such as specific components and different culturing methods,as well as in vivo *** differences in their protein compositions were identified by proteomic ***,the fate of human bone marrow mesenchymal stem cells(hBMSCs)also responds to both culturing methods and ***,hBMSCs cultured with DNP-G(3D)differentiated into NP-like cells,while hBMSCs cultured with DAF-G(2D)underwent AF-like differentiation,indicating a close correlation with the native microenvironments of NP and AF cells,***,we found that the integrin-mediated RhoA/LATS/YAP1 signaling pathway was activated in DAF-G(2D)-induced AF-specific ***,the activation of YAP1 determined the tendency of NP-or AF-specific differentiation and played opposite regulatory ***,DNP-G and DAF-G specifically promoted tissue regeneration in NP degeneration and AF defect rat models,*** conclusion,DNP-G and DAF-G can specifically determine the fate of stem cells through the integrin-mediated RhoA/LATS/YAP1 signaling pathway,and this tissue specificity is both compositional and spatial,supporting the utilization of tissue-specific DTM in advanced treatments of intervertebral disc degeneration.

关键词： tissue specificity Decellularized tissue matrix Intervertebral disc Differentiation YAP1

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Role of the CXCR4-SDF1-HMGB1 pathway in the directional migration of cells and regeneration of affected organs

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World Journal of stem cells 2020年第9期12卷 938-951页

作者： Nazmul Haque Ismail M Fareez Liew Fong Fong Chanchal Mandal Noor Hayaty Abu Kasim Kranthi RajaKacharaju Pratiwi Soesilawati Department of Oral Biology and Biomedical Sciences Faculty of DentistryMAHSA UniversitySelangor 42610Malaysia Biotechnology and Genetic engineering Discipline Life ScienceKhulna UniversityKhulna 9208Bangladesh Faculty of Dentistry University Kebangsaan MalaysiaKuala Lumpur 50300Malaysia Faculty of Dental Medicine Universitas AirlanggaSurabaya 411007Indonesia Department of Conservative Dentistry Faculty of Dentistry MAHSA UniversitySelangor 42610Malaysia Department of Oral Biology Faculty of Dental MedicineUniversitas AirlanggaSurabaya 60115Indonesia

In recent years,several studies have reported positive outcomes of cell-based therapies despite insufficient engraftment of transplanted *** findings have created a huge interest in the regenerative potential of paracrine factors released from transplanted stem or progenitor ***,this notion has also led scientists to question the role of proteins in the secretome produced by cells,tissues or organisms under certain conditions or at a particular time of regenerative *** studies have revealed that the secretomes derived from different cell types contain paracrine factors that could help to prevent apoptosis and induce proliferation of cells residing within the tissues of affected *** could also facilitate the migration of immune,progenitor and stem cells within the body to the site of *** these different paracrine factors present within the secretome,researchers have given proper consideration to stromal cell-derived factor-1(SDF1)that plays a vital role in tissue-specific migration of the cells needed for *** researchers recognized that SDF1 could facilitate site-specific migration of cells by regulating SDF1-CXCR4 and/or HMGB1-SDF1-CXCR4 pathways which is vital for tissue *** in this study,we have attempted to describe the role of different types of cells within the body in facilitating regeneration while emphasizing the HMGB1-SDF1-CXCR4 pathway that orchestrates the migration of cells to the site where regeneration is needed.

关键词： C-X-C motif chemokine 12 Mesenchymal stem cells Monocytes Neutrophils Peripheral blood mononuclear cells Receptor for advanced glycation end products

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engineering stem cell niches in bioreactors

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World Journal of stem cells 2013年第4期5卷 124-135页

作者： Meimei Liu Ning Liu Ru Zang Shang-Tian Yang Yan Li William G Lowrie Department of Chemical and Biomolecular engineering Ohio State University Department of Chemical and Biomedical engineering FAMU-FSU College of Engineering Florida State University

stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the *** differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as "niches",to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix(synthetic and decellularized), paracrine/autocrine signaling and physical forces(i.e., mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general,bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering.

关键词： stem cell engineering Bioreactor Differentiation Microenvironment Microfluidics

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tissue-engineered constructs for peripheral nerve repair:current research concepts and future perspectives

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Plastic and Aesthetic Research 2015年第1期2卷 213-219页

作者： Alba C.de Luca Wassim Raffoul Francesco Giacalone Maddalena Bertolini Pietro G.di Summa EPFL Centre for NeuroprostheticsLaboratory for Soft Bioelectronic Interfaces1015 LausanneSwitzerland Department of Plastic Reconstructive and Hand SurgeryUniversity Hospital of Lausanne(Centre Hospitalier Universitaire Vaudois)1011 LausanneSwitzerland Department of Hand Surgery and Microsurgery CTO-Maria Adelaide Trauma Center10126 TorinoItaly

Traumatic injuries resulting in peripheral nerve lesions lead to important morbidity with devastating social and economic *** the lesioned nerve cannot be sutured directly,a nerve graft is generally required to bridge the *** autologous nerve grafting is still the first choice for reconstruction,it has the severe disadvantage of the sacrifice of a functional *** in tissue engineering and nerve regeneration may have a dramatic impact on clinical and surgical treatment of such nerve *** authors review the latest concepts in tissue engineering for nerve repair,including scaffold engineering of neural guides,biomaterial modification,cell therapy,growth factors delivery,and electrical *** literature is reviewed in detail,pointing out the most interesting present achievements and perspectives for future clinical *** search of the literature was performed using MEDLINE,Embase,and the Cochrane Library to identify research studies on peripheral nerve regeneration through tissue-engineered *** following medical subject headings were used to carry out a systematic search of the literature:“nerve regeneration”,“stem cells”,“biomaterial”,“extracellular matrix”,“functional regeneration”,“growth factors”and“microchannels”.Included literature was published between 1991 and *** reference lists from the retrieved articles were also reviewed for additional *** total,76 articles were included in this study.

关键词： Cell transplantation extracellular matrix growth factors nerve guidance conduit peripheral nerve repair surface modification

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Nanoengineered hydrogels as 3D biomimetic extracellular matrix with injectable and sustained delivery capability for cartilage regeneration

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Bioactive Materials 2023年第1期19卷 487-498页

作者： Penglei Cui Panpan Pan Ling Qin Xinluan Wang Xiaodong Chen Yonghui Deng Xiaoling Zhang Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200092People’s Republic of China Department of Chemistry Fudan UniversityShanghai200433People’s Republic of China Translational Medicine R&D Center Institute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518057People’s Republic of China Department of Spine Surgery Beijing Jishuitan HospitalPeking University Fourth School of Clinical MedicineBeijing100035People’s Republic of China

The regeneration of articular cartilage remains a great challenge due to the difficulty in effectively enhancing spontaneous ***,the combination of implanted stem cells,suitable biomaterials and bioactive molecules has attracted attention for tissue *** this study,a novel injectable nanocomposite was rationally designed as a sustained release platform for enhanced cartilage regeneration through integration of a chitosan-based hydrogel,articular cartilage stem cells(ACSCs)and mesoporous SiO_(2)nanoparticles loaded with anhydroicaritin(AHI).The biocompatible engineered nanocomposite acting as a novel 3D biomimetic extracellular matrix exhibited a remarkable sustained release effect due to the synergistic regulation of the organic hydrogel framework and mesopore channels of inorganic mSiO_(2)nanoparticles(mSiO_(2)NPs).Histological assessment and biomechanical tests showed that the nanocomposites exhibited superior performance in inducing ACSCs proliferation and differentiation in vitro and promoting extracellular matrix(ECM)production and cartilage regeneration in *** a novel multifunctional biocompatible platform was demonstrated to significantly enhance cartilage regeneration based on the sustained release of AHI,an efficient bioactive natural small molecule for ACSCs chondrogenesis,within the hybrid matrix of hydrogel and mSiO_(2)***,the injectable nanocomposite holds great promise for use as a 3D biomimetic extracellular matrix for tissue regeneration in clinical diagnostics.

关键词： Injectable nanocomposite Mesoporous silica 3D biomimetic extracellular matrix Sustained release of anhydroicaritin Cartilage regeneration

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DNA methylation profile is associated with the osteogenic potential of three distinct human odontogenic stem cells

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Signal Transduction and Targeted Therapy 2018年第1期3卷 322-329页

作者： Tingting Ai Jieni Zhang Xuedong Wang Xiaowen Zheng Xueyan Qin Qian Zhang Weiran Li Wei Hu Jiuxiang Lin Feng Chen Department of Orthodontics School of StomatologyPeking UniversityBeijing 100081China Central laboratory School of StomatologyPeking UniversityBeijing 100081China Present address:Department of Orthodontics Guanghua School and Hospital of Stomatology&Institute of Stomatological ResearchSun Yat-sen UniversityGuangzhouChina

Among the various sources of human autologous stem cells,stem cells isolated from dental tissues exhibit excellent properties in tissue engineering and regenerative ***,the distinct potential of these odontogenic cell lines remains *** this study,we analyzed DNA methylation patterns to determine whether specific differences existed among three different odontogenic cell *** the HumanMethylation450 Beadchip,the whole genomes of human dental pulp stem cells(DPSCs),periodontal ligament stem cells(PDLSCs),and dental follicle progenitor cells(DFPCs)were ***,the osteogenic potential of these cells was evaluated both in vitro and in vivo,and the methylation levels of certain genes related to bone formation differed among the three cell lines.P values less than 0.05 were considered to indicate statistical *** three cell types showed highly similar DNA methylation patterns,although specific differences were *** ontology analysis revealed that one of the most significantly different gene categories was related to bone ***,expression of cell surface epitopes and osteogenic-related transcription factors as well as the bone formation capacity were *** results showed that compared with DFPCs and DPSCs,PDLSCs had higher transcription levels of osteogenic-related factors,a higher in vitro osteogenic potential,and an increased new bone formation capacity in *** conclusion,the results of this study suggested that the differential DNA methylation profiles could be related to the osteogenic potential of these human odontogenic cell ***,the increased osteogenic potential of PDLSCs might aid researchers or clinicians in making better choices regarding tissue regeneration and clinical therapies.

关键词： potential ligament conclusion

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The feasible application ofmicrofluidic tissue/organ-on-a-chip as an impersonator of oral tissues and organs:a direction for future research

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Bio-Design and Manufacturing 2023年第4期6卷 478-506页

作者： Nima Farshidfar Sahar Assar Mohammad Amin Amiri Sarina Sahmeddini Shahram Hamedani Moein Zarei Lobat Tayebi Orthodontic Research Center School of DentistryShiraz University of Medical SciencesShirazIran Section for Oral Ecology and Caries Control Department of Dentistry and Oral HealthAarhus UniversityAarhusDenmark Student Research Committee Shiraz University of Medical SciencesShirazIran Oral and Dental Disease Research Center School of DentistryShiraz University of Medical SciencesShirazIran Department of Polymer and Biomaterials Science Faculty of Chemical Technology and EngineeringWest Pomeranian University of TechnologySzczecinAl.Piastow 4571-311 SzczecinPoland Marquette University School of Dentistry MilwaukeeWI 53233USA

Currently,cell culture models play a key role in determining cell behavior under various ***,the accurate simulation of cellular behavior that imitates the body’s conditions remains a ***,to overcome this obstacle,three-dimensional cell culture models have been *** tissues/organs-on-chips(TOOCs)are new devices that have provided the opportunity to culture cells in a medium that is almost similar to the physiological conditions of the *** can be designed in simple or complex models,which are mostly fabricated by soft *** novel structures have been developed to mimic the conditions of various tissues and organs;however,microfluidic models for oral and dental tissues have not yet been widely *** application of TOOCs for oral tissues/organs can provide the opportunity to study cell interactions with biomaterials used in ***,TOOCs can provide the opportunity to study the cellular interactions and developmental stages of oral tissues/organs more *** review of the current advances in the field of TOOC development for oral tissues provides a comprehensive understanding of this burgeoning concept,shows the progress and applications of these novel models in the imitation of oral tissues/organs thus far,and reveals the limitations that TOOCs ***,it suggests further perspectives for future applications.

关键词： Microfluidics tissue-on-a-chip Organ-on-a-chip Tooth-on-a-chip Oral mucosa-on-a-chip Salivary gland-on-a-chip

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A bioactive material with dual integrin-targeting ligands regulates specific endogenous cell adhesion and promotes vascularized bone regeneration in adult and fetal bone defects

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Bioactive Materials 2023年第2期20卷 179-193页

作者： Dake Hao Ruiwu Liu Tomas Gonzalez Fernandez Christopher Pivetti Jordan Elizabeth Jackson Edwin Samuel Kulubya Hong-Jiang Jiang Hai-Yang Ju Wen-Liang Liu Alyssa Panitch Kit S.Lam JKent Leach Diana L.Farmer Aijun Wang Department of Surgery School of MedicineUniversity of California DavisSacramentoCA95817United States Institute for Pediatric Regenerative Medicine Shriners Hospitals for ChildrenSacramentoCA95817United States Department of Biochemistry and Molecular Medicine School of MedicineUniversity of California DavisSacramentoCA95817United States Department of Biomedical engineering University of California DavisDavisCA95616United States Wendeng Orthopaedic Hospital No.1 Fengshan RoadWendeng264400ShandongChina Department of Orthopaedic Surgery School of MedicineUniversity of California DavisSacramentoCA95817United States

Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone ***,current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration,thus leading to adverse tissue formation and decreased regenerative ***,we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone *** biomaterial works by presenting two synthetic ligands,LLP2A and LXW7,explicitly targeting integrinsα4β1 andαvβ3,respectively,expressed on the surfaces of the cells related to bone formation and vascularization,such as mesenchymal stem cells(MSCs),osteoblasts,endothelial progenitor cells(EPCs),and endothelial cells(ECs).In vitro,the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs,osteoblasts,EPCs,and ECs via integrinα4β1 andαvβ3,*** an adult rat calvarial bone defect model,the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials,such as DLX5^(+)cells,osteocalcin^(+)cells,CD34^(+)/CD45-cells and CD31^(+)*** a fetal sheep spinal bone defect model,the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse *** innovative biomaterial offers an off-the-shelf,easy-to-use,and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.

关键词： Integrin-based ligands Endogenous stem cells Bone formation Vascularization Adult and fetal bone defects

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Activity of the Mechanically Isolated Hybrid Stromal Vascular Fraction on Osteoarthritis

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International Journal of Clinical Medicine 2023年第11期14卷 505-524页

作者： Polen Koçak Serli Canikyan Yağiz Denizci Burak Beksaç Yaren Kul Tunç Tiryaki Biomedical engineering Istinye University Istanbul Turkey Genetics and Bioengineering Yeditepe University Istanbul Turkey Faculty of Medicine Medipol University Istanbul Turkey Private Practise Clinic Istanbul Turkey Bioengineering Yildiz Technical University Istanbul Turkey Cadogan Clinic London UK

Background: Regenerative medicine holds promise for treating degenerative and inflammatory conditions like osteoarthritis (OA). However, the complex molecular mechanisms of OA and the limitations of current therapies remain challenges. Adipose-derived stem cells (ADSC) and stromal vascular fraction (SVF) are gaining attention for OA treatment due to their abundance in adipose tissue. The literature delineates two primary techniques for SVF extraction from adipose tissue: enzymatic digestion and mechanical methods. The Lipocube Hybrid SVF presents a straightforward and secure mechanical isolation method for SVF, enhancing its regenerative potential for various applications. Purpose: This study aims to provide valuable insights into the potential of Lipocube Hybrid SVF as a regenerative therapy for OA, contributing to the broader understanding of its applicability in addressing this debilitating condition. Method: To assess the effectiveness and safety of the Lipocube Hybrid SVF, we have designed a comparative study that evaluates cellular activity and viability, phenotypic characterization, and differentiation potential. The in vitro activity of mechanically isolated SVF is compared to the established gold standard enzymatic digestion method. After in vitro studies, Lipocube Hybrid mechanical isolation method was used to isolate SVF and applied in 42 knee and 7 hip joints of 28 patients with Grade II, Grade III, and Grade IV OA. Results: The Lipocube Hybrid group had slightly lower viable cell numbers but higher cell viability. Flow cytometry analysis showed the Lipocube Hybrid group exhibited more favorable markers for regenerative potential and reduced inflammatory response. Additionally, both groups demonstrated successful osteogenic differentiation, with the Lipocube Hybrid group excelling in chondrogenic and adipogenic differentiation. The clinical application of the Lipocube Hybrid SVF in OA patients resulted in significant improvements in WOMAC and VAS scores

关键词： Osteoarthritis Stromal Vascular Fraction Enzymatic Isolation Mechanical Isolation Regenerative Medicine

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Adenosine monophosphate enhances callus regeneration competence for de novo plant organogenesis

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Molecular Plant 2023年第12期16卷 1867-1870页

作者： Hong Gil Lee Seo Young Jang Eun Yee Jie Seung Hee Choi Ok-Sun Park Soon Hyung Bae Hyun-Soon Kim Suk Weon Kim Geum-Sook Hwang Pil Joon Seo Department of Chemistry Seoul National UniversitySeoul 08826Korea Plant Genomics and Breeding Institute Seoul National UniversitySeoul 08826Korea Integrated Metabolomics Research Group Western Seoul CenterKorea Basic Science InstituteSeoul 03759Korea Biological Resource Center Korea Research Institute of Bioscience and BiotechnologyJeongeup56212Korea Plant Systems engineering Research Center Korea Research Institute of Bioscience and BiotechnologyDaejeon 34141Korea College of Pharmacy Chung-Ang UniversitySeoul 06974Korea

Dear Editor,Plant tissue culture involves callus formation and de novo shoot ***,explants from differentiated tissues are used to generate a pluripotent cell mass,called callus,on auxin-rich callus-inducing medium(CIM),followed by shoot regeneration on cytokinin-rich shoot-inducing medium(SiM).Callus results from division of pericycle-like cells(Atta et al.,2009;Sugimoto et al.,2010);its cellular identity resembles that of lateral root primordia(Atta et al.,2009;Sugimoto et al.,2010).Callus acquires cellular pluripotency by forming root stem cell niches on CIM(Sugimoto et al.,2010)。

关键词： Adenosine callus

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