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Genes & Diseases 2024年第3期11卷 26-29页

作者： Xiangyu Dong Yannian Gou Meichun Guo Jiamin Zhong Aohua Li Ailing Hao Wei Zeng rex C.Haydon Hue H.Luu russell r.reid Tongchuan He Yan Xu Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistryCollege of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Institute of Sports Medicine Beijing Key Laboratory of Sports InjuriesPeking University Third HospitalBejing 100191China

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport *** for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

关键词： transport methods simplified

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow russell r.reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow russell r.reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LrP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

Molecular basis of cranial suture biology and disease:Osteoblastic and osteoclastic perspectives

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Genes & Diseases 2014年第1期1卷 120-125页

作者： Maureen Beederman Evan M.Farina russell r.reid Section of Plastic&reconstructive Surgery Department of SurgeryThe University of Chicago Medical Center5841 South Maryland AvenueMC 6035ChicagoIL 60637USA Pritzker School of Medicine and The Laboratory of Craniofacial BiologyUniversity of Chicago MedicineChicagoIL 60637USA

The normal growth and development of the skull is a tightly regulated process that occurs along the osteogenic interfaces of the cranial ***,the borders of the calvarial bones and neighboring tissues above and below,function as a *** coordinated remodeling efforts of bone deposition and resorption,the cranial sutures maintain a state of patency from infancy through early adulthood as the skull continues to grow and accommodate the developing brain’s demands for ***,when this delicate balance is disturbed,a number of pathologic conditions ensue;and if left uncorrected,may result in visual and neurocognitive impairments.A prime example includes craniosynostosis,or premature fusion of one or more cranial and/or facial suture(s).At the present time,the only therapeutic measure for craniosynostosis is surgical correction by cranial vault ***,elegant studies performed over the past decade have identified several genes critical for the maintenance of suture patency and induction of suture *** deeper understandings of the pathogenesis and molecular mechanisms that regulate suture biology may provide necessary insights toward the development of non-surgical therapeutic alternatives for patients with cranial suture *** this review,we discuss the intricate cellular and molecular interplay that exists within the suture among its three major components:dura mater,osteoblastic related molecular pathways and osteoclastic related molecular pathways.

关键词： Cranial sutures Craniosynostosis Dura mater Osteoblasts Osteoclasts

Transgenic PDGF-BB sericin hydrogel potentiates bone regeneration of BMP9-stimulated mesenchymal stem cells through a crosstalk of the Smad-STAT pathways

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regenerative Biomaterials 2023年第1期10卷 181-193页

作者： Hui-Jie Zhang Fu-Shu Li Feng Wang Han Wang Tong-Chuan He russell r.reid Bai-Cheng He Qingyou Xia Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing Chongqing Medical UniversityChongqing 400016China Department of Pharmacology School of PharmacyChongqing Medical UniversityChongqing 400016China Department of Pharmacy Chongqing Emergency Medical CenterChongqing University Central HospitalChongqing 400014China Biological Science research Center Chongqing Key Laboratory of Sericultural ScienceChongqing Engineering and Technology Research Center for Novel Silk MaterialsSouthwest UniversityChongqing 400715China Department of Pharmacy Panzhou People’s HospitalGuizhou 553599China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Silk as a natural biomaterial is considered as a promising bone substitute in tissue *** and fibroin are the main components of silk and display unique features for their programmable mechanical properties,biocompatibility,biodegradability and morphological *** has been reported that sericin recombinant growth factors(GFs)can support cell proliferation and induce stem cell differentiation through cross-talk of signaling pathways during tissue *** transgenic technology allows the productions of bioactive heterologous GFs as fusion proteins with sericin,which are then fabricated into solid matrix or hydrogel ***,using an injectable hydrogel derived from transgenic platelet-derived GF(PDGF)-BB silk sericin,we demonstrated that the PDGF-BB sericin hydrogel effectively augmented osteogenesis induced by bone morphogenetic protein(BMP9)-stimulated mesenchymal stem cells(MSCs)in vivo and in vitro,while inhibiting adipogenic *** gene expression and protein-protein interactions studies demonstrated that BMP9 and PDGF-BB synergistically induced osteogenic differentiation through the cross-talk between Smad and Stat3 pathways in ***,our results provide a novel strategy to encapsulate osteogenic factors and osteoblastic progenitors in transgenic sericin-based hydrogel for robust bone tissue engineering.

关键词： biomaterials growth factor BMP9 osteogenesis

Fibroblast growth factor(FGF)signaling in development and skeletal diseases

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Genes & Diseases 2014年第2期1卷 199-213页

作者： Chad M.Teven Evan M.Farina Jane rivas russell r.reid The Laboratory of Craniofacial Biology Section of Plastic&Reconstructive SurgeryDepartment of SurgeryThe University of Chicago Medical Center5841 South Maryland AvenueMC 6035ChicagoIL 60637USA The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA

Fibroblast growth factors(FGF)and their receptors serve many functions in both the developing and adult *** contain 18 FGF ligands and four FGF receptors(FGFr).FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation,differentiation,and migration,morphogenesis,and ***-FGFr signaling is also critical to the developing axial and craniofacial *** particular,the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture *** the adult,FGFs and FGFrs are crucial for tissue *** signaling generally follows one of three transduction pathways:rAS/MAP kinase,PI3/AKT,or *** pathway likely regulates specific cellular *** expression of FGF and improper activation of FGFrs are associated with various pathologic conditions,unregulated cell growth,and ***,aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and *** biology and mechanisms of the FGF family have been the subject of significant research over the past 30 ***,work has focused on the therapeutic targeting and potential of FGF ligands and their associated *** majority of FGF-related therapy is aimed at age-related *** understanding of FGF signaling and biology may reveal additional therapeutic roles,both in utero and *** review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development.

关键词： Craniosynostosis FGF signaling Fibroblast growth factor Fibroblast growth factor receptor Genetics Pathogenesis Signal transduction Skeletal development

Syndromic craniosynostosis associated with microdeletion of chromosome 19p13.12-19p13.2

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Genes & Diseases 2015年第4期2卷 347-352页

作者： Sarah M.Lyon Darrel Waggoner Sara Halbach Erik C.Thorland Leila Khorasani russell r.reid Pritzker School of Medicine University of ChicagoUnited States Department of Human Genetics and Pediatrics University of Chicago5841 S.Maryland AveM/C 0077ChicagoIL 60637United States Lab Medicine&Pathology 200 First St SWHilton 970RochesterMN 55905-0001United States Department of Surgery University of Chicago5841 S.Maryland AveM/C 0077ChicagoIL 60637United States

Craniosynostosis,a condition in which the cranial sutures prematurely fuse,can lead to elevated intracranial pressure and craniofacial abnormalities in young *** surgical intervention is the only therapeutic option for patients with this *** has been associated with a variety of different gene mutations and chromosome *** we describe three cases of partial deletion of chromosome *** of the cases present with syndromic craniosynostosis while one has metopic ridging.A review of the genes involved in the rearrangements between the three cases suggests several gene candidates for *** and DAND5,BMP regulators involved in osteoblast differentiation,and MOrG1,a mediator of osteoclast dysregulation may play a role in abnormal cranial vault ***,CACNA1A,a gene that when mutated is associated with epilepsy and CC2D1A,a gene associated with non-syndromic mental retardation may contribute to additional phenotypic features seen in the patients we *** addition,these findings further support the need for genetic testing in cases of syndromic craniosynostosis.

关键词： Chromosome 19 Craniofacial syndrome Craniosynostosis Microarray Microdeletion

Bone morphogenetic protein-9 effectively induces osteogenic differentiation of reversibly immortalized calvarial mesenchymal progenitor cells

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Genes & Diseases 2015年第3期2卷 268-275页

作者： Chad M.Teven Michael T.rossi Deana S.Shenaq Guillermo A.Ameer russell r.reid The Laboratory of Craniofacial Development and Biology Section of Plastic and Reconstructive SurgeryUniversity of Chicago MedicineChicagoILUSA Department of Biomedical Engineering Northwestern UniversityChicagoILUSA Department of Surgery Northwestern UniversityChicagoILUSA

Critical-sized craniofacial defect repair represents a significant challenge to reconstructive *** strategies have been employed in an effort to achieve both a functionally and cosmetically acceptable *** morphogenetic proteins(BMPs)provide a robust osteoinductive cue to stimulate bony growth and *** studies have suggested that the BMP-9 isoform is particularly effective in promoting osteogenic differentiation of mesenchymal progenitor *** aim of this study is to characterize the osteogenic capacity of BMP-9 on calvarial mesenchymal progenitor cell *** immortalized murine calvarial progenitor cells(iCALs)were infected with adenoviral vectors encoding BMP-9 or GFP and assessed for early and late stages of osteogenic differentiation in vitro and for osteogenic differentiation via in vivo stem cell implantation *** elevations in alkaline phosphatase(ALP)activity,osteocalcin(OCN)mrNA transcription,osteopontin(OPN)protein expression,and matrix mineralization were detected in BMP-treated cells compared to ***,ALP activity was elevated on days 3,7,9,11,and 13 post-infection and OCN mrNA expression was elevated on days 8,10,and 14 in treated ***,treatment groups demonstrated increased OPN protein expression on day 10 and matrix mineralization on day 14 post-infection relative to control ***-9 also facilitated the formation of new bone in vivo as detailed by gross,microcomputed tomography,and histological ***,we concluded that BMP-9 significantly stimulates osteogenic differentiation in iCALs,and should be considered an effective agent for calvarial tissue regeneration.

关键词： Bone morphogenetic protein(BMP) Bone morphogenetic protein-9(BMP-9) Immortalized calvarial cell(iCAL) Mesenchymal progenitor cell Osteogenic capacity Osteogenic differentiation

Stem cells, growth factors and scaffolds in craniofacial regenerative medicine

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Genes & Diseases 2016年第1期3卷 56-71页

作者： Viktor Tollemar Zach J.Collier Maryam K.Mohammed Michael J.Lee Guillermo A.Ameer russell r.reid The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Department of Orthopedic Surgery and rehabilitation Medicine The University of Chicago Medical CenterChicagoIL 60637USA Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago MedicineChicagoIL 60637USA Department of Surgery Feinberg School of MedicineChicagoIL 60611USA Biomedical Engineering Department Northwestern UniversityEvanstonIL 60208USA

Current reconstructive approaches to large craniofacial skeletal defects are often complicated and ***-sized defects are unable to heal via natural regenerative processes and require surgical intervention,traditionally involving autologous bone(mainly in the form of nonvascularized grafts)or *** bone grafts remain the gold standard of care in spite of the associated risk of donor site *** engineering approaches represent a promising alternative that would serve to facilitate bone regeneration even in large craniofacial skeletal *** strategy has been tested in a myriad of iterations by utilizing a variety of osteoconductive scaffold materials,osteoblastic stem cells,as well as osteoinductive growth factors and small *** of the major challenges facing tissue engineers is creating a scaffold fulfilling the properties necessary for controlled bone *** properties include osteoconduction,osteoinduction,biocompatibility,biodegradability,vascularization,and progenitor cell *** review will provide an overview of how optimization of the aforementioned scaffold parameters facilitates bone regenerative capabilities as well as a discussion of common osteoconductive scaffold materials.

关键词： Bone regeneration Craniofacial defects Osteogenesis regenerative medicine Scaffolds Tissue engineering

3-D bioprinting technologies in tissue engineering and regenerative medicine:Current and future trends

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Genes & Diseases 2017年第4期4卷 185-195页

作者： Elliot S.Bishop Sami Mostafa Mikhail Pakvasa Hue H.Luu Michael J.Lee Jennifer Moriatis Wolf Guillermo A.Ameer Tong-Chuan He russell r.reid Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago MedicineChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Biomedical Engineering Department Northwestern UniversityEvanstonIL 60208USA Department of Surgery Feinberg School of MedicineNorthwestern UniversityChicagoIL 60616USA

Advances in three-dimensional(3D)printing have increased feasibility towards the synthesis of living *** as 3D bioprinting,this technology involves the precise layering of cells,biologic scaffolds,and growth factors with the goal of creating bioidentical tissue for a variety of *** successes have demonstrated distinct advantages over conventional tissue engineering *** surprisingly,there are current challenges to address before 3D bioprinting becomes clinically *** we provide an overview of 3D bioprinting technology and discuss key advances,clinical applications,and current *** 3D bioprinting is a relatively novel tissue engineering strategy,it holds great potential to play a key role in personalized medicine.

关键词： Additive manufacturing Bioprinting CAD/CAM 3D printing Tissue engineering