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Nature Classic: Scientists Successfully Construct Thymus With Stem Cells

source:Qida organism  views:2063  time:2020-12-18

Researchers At Francis Crick Institute And University College London (UCL) Reconstructed The Human Thymus Using Human Stem Cells And Bioengineered Scaffolds. The Thymus Is An Important Organ In The Immune System, Which Marks An Important Step Towards Building An Artificial Thymus For Transplantation. Dr. Sara Campinotti, A Researcher In The Epithelial Stem Cell Biology And Regenerative Medicine Laboratory Of Crick Research Institute, Said: "It Is Proved That It Is Possible To Establish A Normal Thymus From Human Cells, Which Is A Key Step Towards Cultivating Thymus. Thymus Can Be Used For Transplantation One Day."; The First Author Campinoti And His Colleagues Concluded In The Report In Nature Communications ("Reconstruction Of Functional Human Thymus Through Postnatal Interstitial Progenitor Cells And Natural Whole Organ Scaffolds"), "This Is An Important Original Proof That The Long-life Phenomenon Of Human Thymus Is Only Used After Birth, And Cultured Cells Can Be Constructed."  The Thymus Is A Major Lymphoid Organ Located In The Chest, Which Is Crucial For The Maturation And Selection Of T Cells. When The Thymus Function Is Abnormal, Or Organs Are Not Formed During Fetal Development, The Results Include Serious Immune Deficiency, That Is, The Body Cannot Resist Infectious Diseases Or Cancer Cells, Or Spontaneous Immune Disorder, And The Immune System Wrongly Attacks The Patient's Own Healthy Tissues. The Researchers Continued To Say: "Because The Thymus Controls The Development Of Immunity And Immune Tolerance, Its Functional Isolation And Subsequent Reconstruction With The Required Cell Population May Provide A Powerful Tool For Many Medical Conditions, Including Primary Or Acquired Immunodeficiency." In Fact, The Cultured Thymus Sections Are Currently Used For Transplantation Of Patients Without Thymus, But The Clinical Needs Have Not Been Met& Nbsp; However, The Author Points Out That So Far, Attempts To Build A Fully Functional Thymus Have Only Had "limited Success", Possibly Because The Organ Is Too Complex. However, They Also Pointed Out That This May Be Achieved By Using Postnatal Epithelial Stem/progenitor Cells And Mesenchymal Cells, But There Are Still Some "uncertainties", Such As Whether These Cells Can Be Expanded In Sufficient Quantities In Vitro. In Their Latest Proof Of Concept Study, Scientists Described How They Successfully Reconstructed The Thymus With Stem Cells Extracted From Patients With Organs Removed During Surgery. When Bioengineered Thymus Is Transplanted Into Mice, It Can Support The Development Of Mature And Functional Human T Lymphocytes. Therefore, Former Scientists Believe That They Have Successfully Reconstructed The Whole Thymus Organ& Nbsp;& Nbsp; In Order To Create Complete Organs, Researchers First Collected Thymus From Patients Undergoing Open Heart Surgery, And Then Cultured Thymic Epithelial Cells (TEC) And Thymic Interstitial Cells (TIC) From Donated Tissues Into Billions Of Cell Colonies In The Laboratory. The Next Step Is To Obtain The Structural Scaffold Of The Thymus, And They Reproduce With The Cultured Thymocytes. To This End, The Collaborator Dr. Asllan Gjinovci, A Senior Laboratory Research Scientist Of Crick, Developed A New Method To Remove All Cells In The Rat Thymus, Leaving Only The Structural Scaffold. The Researchers Had To Use A New Microvascular Surgery Method To Treat The Thymus, Because The Traditional Method Has No Effect On The Thymus. Gjinovci Commented, "This New Method Is Very Important Because It Enables Us To Obtain Scaffolds From Larger Organs (such As Human Thymus), Which Is Essential To Bring This Beautiful Achievement To Clinical Practice."; Then, When The Researchers Injected Thymic Epithelial Cells And Thymic Stromal Cells From The Colonies They Grew In The Laboratory Into The Organ Scaffold, The Cells Began To Grow On The Scaffold, And Only Five Days Later, The Organ Developed To A Stage Similar To That Of A 9-week Old Fetus. "It Is Possible To Cultivate Organ Size, Three-dimensional Structure Supporting The Survival Of Thymic Stromal Cells And Appropriate Spatial Tissue, Thus Promoting The Differentiation Of Thymocytes," The Authors Commented& Nbsp; When The Research Team Implanted The Laboratory Grown Thymus Into "humanized" Mice, They Found That In More Than 75% Of The Transplants, The Thymus Could Support The Development Of Human Lymphocytes. One Of The Authors, Dr. Roberta Ragazzini, Is A Postdoctoral Research Scientist At Crick Research Institute. He Further Pointed Out: "The Fact That We Can Widely Expand Thymic Stem Cells From Human Donors To Large Colonies Is Really Exciting. This Makes It Possible To Expand This Process To Build 'human Size' Thymus." The Team Believes That This Work Represents An Important Step, It Not Only Can Further Study And Treat Severe Immunodeficiency, But Also Has Wider Significance For Developing New Technologies For Artificial Organ Growth. As The Author Concluded, "The Data Described In This Study And Clinical Data Show That Postpartum Human Thymic Epithelial Cells (TEC) And Interstitial Cells (TIC) Can Be Expanded In Vitro, Which Is Suitable For Reconstruction Of Human Like Functional Thymus... By Overcoming The Obstacle Function, The Thymus Can Only Expand. Postnatal Donor Stromal Cells Are A Tool For Us To Find Immune Diseases With Limited Treatment Methods At Present, Including Providing A Practical Prospect For Patients With Congenital Absence Of Thymus."  Scientists Are Continuing To Improve And Expand The Process Of Rebuilding Thymi. "In Addition To Providing A New Source Of Transplantation For People With Thymic Insufficiency, Our Work Has Other Potential Applications In The Future," Said Dr. Paola Bonfanti, Senior Author And Team Leader Of Crick And Professor Of Infection And Immunity At University College London. "For Example, The Thymus Helps The Immune System Recognize Itself From Non Self, Which Brings Problems To Organ Transplantation, Because It Will Cause The Immune System To Attack The Transplanted Organ. It Is Possible To Overcome This Problem By Transplanting Thymus Regenerative Cells From The Thymus Cells Of Organ Donors. We Believe That This May Prevent The Body From Attacking Transplantation. The Research Behind This Is Still At An Early Stage, But It Is An Exciting Concept That Can Make Patients No Longer Need Immunosuppressants For The Rest Of Their Lives.
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