Lung organoids are human stem cell-derived mini lungs in a laboratory dish.
Since the COVID-19 pandemic reached the United States in early 2020, scientists have struggled to find laboratory models of SARS-CoV-2 infection, the respiratory virus that causes COVID-19. Animal models fell short; attempts to grow adult human lungs have historically failed because not all of the cell types survived.
Undaunted, stem cell scientists, cell biologists, infectious disease experts and cardiothoracic surgeons at University of California San Diego School of Medicine teamed up to see if they could overcome multiple hurdles.
Writing in a paper publishing August 31, 2021 in eLife, the team describes the first adult human lung-in-a-dish models, also known as lung organoids that represent all cell types. They also report that SARS-CoV-2 infection of the lung organoids replicates real-world patient lung infections, and reveals the specialized roles various cell types play in infected lungs.
This human disease model will now allow us to test drug efficacy and toxicity, and reject ineffective compounds early in the process, at Phase 0, before human clinical trials begin, said Pradipta Ghosh, MD, professor, director of the Institute for Network Medicine and executive director of the HUMANOID Center of Research Excellence (CoRE) at UC San Diego School of Medicine. Ghosh co-led the study with Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine and founding co-director and chief scientific officer of HUMANOID CoRE.
Stem cell scientists at the HUMANOID CoRE, led by Das, reproducibly developed three lung organoid lines from adult stem cells derived from human lungs that had been surgically removed due to lung cancer. With a special cocktail of growth factors, they were able to maintain cells that make up both the upper and lower airways of human lungs, including specialized alveolar cells known as AT2.
By infecting the lung organoids with SARS-CoV-2, the team discovered that the upper airway cells are critical for the virus to establish infection, while the lower airway cells are important for the immune response. Both cell types contribute to the overzealous immune response, sometimes called a cytokine storm that has been observed in severe cases of COVID-19.
A computational team led by Debashis Sahoo, PhD, assistant professor of pediatrics at UC San Diego School of Medicine and of computer science and engineering at Jacobs School of Engineering, validated the new lung organoids by comparing their gene expression patterns which genes are on or off to patterns reported in the lungs of patients who succumbed to the disease, and to those that they previously uncovered from databases of viral pandemic patient data.
Whether infected or not with SARS-CoV-2, the lung organoids behaved similar to real-world lungs. In head-to-head comparisons using the same yardstick (gene expression patterns), the researchers showed that their adult lung organoids replicated COVID-19 better than any other current lab model. Other models, for example fetal lung-derived organoids and models that rely only on upper airway cells, allowed robust viral infection, but failed to mount an immune response.
Our lung organoids are now ready to use to explore the uncharted territory of COVID-19, including post-COVID complications, such as lung fibrosis, Das said. We have already begun to test drugs for their ability to control viral infection from entry to replication to spread the runaway immune response that is so often fatal, and lung fibrosis.
Since their findings in human organoids are more likely to be relevant to human disease than findings in animal models or cell lines, the team hopes that successful drug candidates can be rapidly progressed to clinical trials.
Because our HUMANOID CoRE lung organoids are scalable, personalized, propagatable and cost-effective, they are quite unlike any other existing model, said Ghosh. This is a significant advance that can enable the modeling of lung diseases and pandemics beyond COVID-19. In fact, other academic and industry partners are already beginning to use these organoids in disease modeling and drug discovery. This is when I feel that translational research is immediately transformative.
Co-authors include: Courtney Tindle, MacKenzie Fuller, Ayden Fonseca, Sahar Taheri, Stella-Rita Ibeawuchi, Gajanan Dattatray Katkar, Amanraj Claire, Vanessa Castillo, Moises Hernandez, Hana Russo, Jason Duran, Ann Tipps, Grace Lin, Patricia A. Thistlethwaite, Thomas F. Rogers, UC San Diego; Nathan Beutler, Scripps Research; Laura E. Crotty Alexander, UC San Diego and VA San Diego Healthcare System; Ranajoy Chattopadhyay, UC San Diego and Cell Applications, Inc.
Funding for this research came, in part, from the National Institutes for Health (grants 1R01DK107585-01A1, 3R01DK107585-05S1, R01-AI141630, CA100768, CA160911, R01-AI 155696, R00-CA151673, R01-GM138385, R01-HL32225, UCOP-R00RG2642, UCOP-R01RG3780), Sanford Stem Cell Clinical Center at UC San Diego Health and VA San Diego Healthcare System.
- COVID-19: Researchers warn against overhyping early-stage therapies - Medical News Today - October 26th, 2021
- OpRegen Data Update to Be Featured at 2021 American Academy of Ophthalmology Annual Meeting in Presentation by Michael S. Ip, M.D. - Yahoo Finance - October 26th, 2021
- Insights & Outcomes: Place cells, planarians, and 'prewet' proteins - Yale News - October 26th, 2021
- IMAC Holdings The Back Space Announces the Completion of Two Additional Retail Spinal Care Locations - Yahoo Finance - October 26th, 2021
- JEFFERSON PARISH PARTNERS WITH LOUISIANA DEPARTMENT OF HEALTH TO ADMINISTER FREE FLU SHOTS AND COVID-19 VACCINES ON NOVEMBER 6, 2021 - 10-25-YYYY -... - October 26th, 2021
- Male Infertility Could Be Treated With Monkey Cells; New Study Shows How These Animals Could Help Address the Condition - Science Times - October 26th, 2021
- Citius Pharmaceuticals to Host Key Opinion Leader Webcast on the Compelling Need to Salvage Central Venous Catheters in CLABSI Patients - Yahoo... - October 26th, 2021
- New findings may help widen therapeutic interventions for B-cell acute lymphoblastic leukemia - News-Medical.Net - October 25th, 2021
- Getting to Know Kate Roth at Beacon Integrative Medical Center in Rexburg - East Idaho News - October 25th, 2021
- Global Cell Therapy Market Report 2021-2028 - Growing Adoption of Regenerative Medicine & Introduction of Novel Platforms and Technologies -... - October 25th, 2021
- Vertex reports positive results for first patient in Type 1 diabetes trial - BetaBoston - October 23rd, 2021
- Morris receives grant for stem cell research - The Source - Washington University Record - October 23rd, 2021
- Vertex moves ahead with its bid to develop a curative treatment for type 1 diabetes - PMLiVE - October 23rd, 2021
- McLaughlin Research Institute receives $5 million gift to support neurology studies - Great Falls Tribune - October 23rd, 2021
- AML medication and treatment: What to know - Medical News Today - October 23rd, 2021
- U S Stem Cell : USRM to Focus on Animal Health and Lead Pet-Care Innovation - Marketscreener.com - October 19th, 2021
- Opinion: Why Colin Powell's death should not be framed as the death of a vaccinated person - Poynter - October 19th, 2021
- Quris combines AI with patient on a chip to speed drug development and reduce animal testing - TechCrunch - October 19th, 2021
- Dr. Helen Heslop elected to the National Academy of Medicine - Baylor College of Medicine News - October 19th, 2021
- Researchers report long-lasting effects of gene therapy in children with deadly immune disorder - News-Medical.Net - October 19th, 2021
- Coronavirus: How does misinformation spread, and how can we stop it? - The Jerusalem Post - October 17th, 2021
- Dr. Kahl on the Potential Utility of Frontline CAR T-Cell Therapy in MCL - OncLive - October 17th, 2021
- FDA Approves Genentech's Tecentriq as Adjuvant Treatment for Certain People With Early Non-Small Cell Lung Cancer - Business Wire - October 17th, 2021
- Global Stem Cell and Primary Cell Culture Medium Market 2021 Trends and Leading Players Analysis 2027 Merck, STEMCELL Technologies, Irvinesci, Cell... - October 15th, 2021
- Dr. Erba on the Evolution of Treatment in MCL - OncLive - October 15th, 2021
- After no stem cell donors stepped up to saved her son, mom continues to help others facing the same challenge - Chicago Tribune - October 15th, 2021
- International ZIM Network: SmartMed - Regenerative Solutions for the Therapies of Tomorrow - Business Wire - October 15th, 2021
- Are 'robot massages' the future of muscle repair? - Medical News Today - October 15th, 2021
- What the FDA Panel's Moderna Booster Shot Vote Means and What's Next - NBC Chicago - October 15th, 2021
- Phase 2 Clinical Trial Data of NurOwn in Progressive MS Will Be Presented at the 37th Congress of the European Committee for Treatment and Research in... - October 15th, 2021
- R3 Stem Cell & Exosome Therapy: Joint & Back Pain, Avoid ... - October 13th, 2021
- Stem Cell PhD Program | Institute for Stem Cell Biology ... - October 13th, 2021
- New stem cell identified by Sanford Burnham Prebys researchers offers hope to people with rare liver disease - Newswise - October 13th, 2021
- Repurposed Drug Reverses Signs of Alzheimers in Mice, Human Cells - The Scientist - October 13th, 2021
- Bone Therapeutics appoints Scientific Advisory Board for iMSC cell and gene therapy platform development - StreetInsider.com - October 13th, 2021
- What the latest COVID research says about breakthrough cases and transmission : Shots - Health News - NPR - October 13th, 2021
- HNF collaborates with Rarebase on a Drug Discovery Platform to develop treatments for Charcot-Marie-Tooth (CMT) - PRNewswire - October 13th, 2021
- Autologous HSCT Continues to Show Sustained Benefit in MCL, But Targeted Therapies May Challenge its Role as Standard Frontline Treatment -... - October 13th, 2021
- Bartolo Coln, Winner Of The Cy Young, Wins Lawsuit In Case Of Stem Cell Treatment To Which He Was Subjected Before His Return To The Major Leagues. -... - October 11th, 2021
- The Impact Of Market Restrictions On The US Stem Cell Biomaterials Market - Med Device Online - October 11th, 2021
- Vitro Biopharma Inc. July 31st 2021; 3rd Quarter ended Financial Results of Operations and Shareholder Letter. - Yahoo Finance - October 11th, 2021
- Top US Leukemia Experts from Academia, Industry and Public Sector Coming Together at Acute Myeloid Leukemia Conference on October 22 - OncLive - October 11th, 2021
- Precision medicine data dive shows water pill may be viable to test as Alzheimer's treatment - National Institutes of Health - October 11th, 2021
- Treating Early Relapse in Follicular Lymphoma - Targeted Oncology - October 11th, 2021
- Humans and Chimpanzees Use a Part of Their DNA in Different Ways - Technology Networks - October 11th, 2021
- A stem cell treatment for MS offers some patients hope. But is it hope that will last? - WHYY - October 9th, 2021
- CAR T Offer New Treatment Option for Non-Hodgkin Lymphoma - Targeted Oncology - October 9th, 2021
- FDA Advisory Committee Recommends Maribavir to Treat Cytomegalovirus CMV Infection and Disease - Contagionlive.com - October 9th, 2021
- What surgeons are saying about regenerative medicine in 2021 - Becker's Orthopedic & Spine - October 9th, 2021
- Study illuminates how BRD4 protein directs the spatial organization of DNA within cell nucleus - News-Medical.net - October 9th, 2021
- Cellular Therapy Strategies Offer the Prospect of Deep Remissions for Multiple Myeloma - OncLive - October 9th, 2021
- Anti-CD47 Therapy and Other New Approaches to the Treatment of Myelodysplastic - Targeted Oncology - October 9th, 2021
- ViaCyte to Present at Alliance for Regenerative Medicine Cell & Gene Meeting on the Mesa - PRNewswire - October 7th, 2021
- Seattle Stem Cell Therapy Clinic - Seattle Sports Medicine ... - October 7th, 2021
- StemExpress Partners with the Alliance for Regenerative Medicine to Provide COVID-19 Testing for the Cell and Gene Meeting on the Mesa - PRNewswire - October 7th, 2021
- New Stem Cell Approach Through Using Wavelength Laser Might have Discovered Why Humans Lose Hair - Tech Times - October 5th, 2021
- Faster healing of wounds can decrease pain and suffering and save lives - WMTV - NBC15 - October 5th, 2021
- Losing Your Hair? You Might Blame the Great Stem Cell Escape. - The New York Times - October 5th, 2021
- Northwesterns SPORE has made advances in understanding the genetic basis of glioblastoma - News-Medical.Net - October 5th, 2021
- NextCure Announces New Appointments to its Board of Directors - GlobeNewswire - October 5th, 2021
- Therapy and Prevention Strategies for Myocardial Infarction | IJN - Dove Medical Press - October 3rd, 2021
- Lack of awareness about blood stem cell donation is one of the leading causes for low number of donors in In.. - ETHealthworld.com - October 3rd, 2021
- Advanced technique offers new insights about the dynamics of gliomas - News-Medical.net - October 3rd, 2021
- "Stem cell-based therapeutics poised to become mainstream option - BSA bureau - October 2nd, 2021
- The stem cell revolution isnt what you think it is - New Scientist News - October 2nd, 2021
- Stem cell agency gives out $2 million a minute - Capitol Weekly - October 2nd, 2021
- Researching the Safety and Effectiveness of Stem Cells to Treat 'Long Covid' - Entrepreneur - October 2nd, 2021
- United States Regenerative Medicine Markets to 2026: Focus on Cell Therapies, Gene Therapies, Progenitor & Stem Cell Therapies, Tissue Engineered... - October 2nd, 2021
- U.S. FDA Approves Kite's Tecartus as the First and Only Car T for Adults With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia - Business... - October 2nd, 2021
- Omeros Provides Regulatory Update on Biologics License Application for Narsoplimab in the Treatment of HSCT-TMA - Business Wire - October 2nd, 2021
- Stem Cell Umbilical Cord Blood Market in North America 2021 Sees Growth Due to Rising Spending Capacity and Suitable Payment Plans - PRNewswire - October 2nd, 2021
- BrainStorm to Present Phase 2 Progressive MS Study Results in Oral Presentation at 37th Congress of ECTRIMS - BioSpace - October 2nd, 2021
- Macomics Announces New Hires that Expands its Macrophage-based Drug Discovery R&D Team - BioSpace - October 2nd, 2021
- Stanford neuroscientist's 'assembloids' pave the way for innovative brain research - Scope - October 2nd, 2021
- At the crossroads of reproductive and regenerative medicine: new opportunities for preserving and restoring fertility - ESHRE - September 25th, 2021
- Doctors Debate: Do CAR T Cells and Transplantation Both Have a Place in Aggressive B-Cell Lymphoma Treatment? - Targeted Oncology - September 25th, 2021
- Global Stem Cell Alopecia Treatment Market 2021 Development Status,Industry Insights and Forecast Research Report 2027 Stillwater Current -... - September 25th, 2021
- AML vs. ALL: Differences in symptoms, diagnosis, and survival - Medical News Today - September 25th, 2021
- New gene therapies may soon treat dozens of rare diseases - American Society for Biochemistry and Molecular Biology - September 25th, 2021
- BioRestorative Therapies Receives Notice of Allowance for Patent Application in Israel for its Metabolic Program - GlobeNewswire - September 25th, 2021