Spheroid Stem Cell Production Sows Hope for IPF Treatment

In a small pilot study, researchers from North Carolina State University have demonstrated a rapid, simple way to generate large numbers of lung stem cells for use in disease treatment. This method of harvesting and growing a patient’s own lung stem cells shows promise in mice for treating idiopathic pulmonary fibrosis (IPF), and could one day provide human IPF sufferers with an effective, less invasive method of treatment for their disease.

The idea of using the body’s own cells to fight diseases is not new, but current methods of isolating stem cells from bone marrow, fat tissue or cord blood are time consuming, costly and often wasteful. “In current stem cell harvesting, just the process of sorting the stem cells can damage them, wasting not only the cells, but also time and money,” says Ke Cheng, lead researcher on the project. “We wanted to see if we could take healthy stem cells from an organ while they were still in a supportive environment, recreate and enhance that environment outside the body to encourage stem cell reproduction, then reintroduce those cells into a damaged organ to treat disease.” Cheng is an associate professor of regenerative medicine at NC State’s College of Veterinary Medicine and the UNC-Chapel Hill/NC State joint department of biomedical engineering.

Lung stem cells (green and red) residing in a cultured lung spheroid.
Lung stem cells (green and red) residing in a cultured lung spheroid.

Instead of attempting to isolate and sort individual lung stem cells or genetically convert other types of cells into lung stem cells, Cheng used a multicellular spheroid method to harvest and grow them. A spheroid is a three-dimensional cellular structure that has typically been used to culture cancer cells or embryonic stem cells for experimentation and research. The cells of interest – in Cheng’s research, lung stem cells – are at the center of the spheroid, and they are surrounded by layers of supporting cells.

“We’re the first lab to show that the spheroid environment can be used to enrich adult lung stem cells. In the spheroid, we recreate the stem cells’ natural microenvironment, the “niche,” where they can communicate with each other just as they would inside your body,” says Cheng. “There is no use of exogenous or transgenic materials – the stem cells are 100 percent the donor’s own genetic material, a perfect match to the patient and the organ being treated.”

In a small animal trial, Cheng and his graduate students tested the spheroid-produced human lung stem cells on mice with IPF, a fatal disease that thickens and scars healthy lung tissue, creating inflammation and replacing the lining of the lung cells with fibroids. “This was a proof of concept trial. The mice that received the stem cell transplant showed decreases in inflammation and fibrosis – their lungs almost matched those of the control group, who did not have IPF at all,” says Cheng. “And the beauty of the process is that the cell therapy can be delivered intravenously.

“Picture the lung as a garden and the stem cells as seeds. In an IPF environment, with inflammation, the soil is bad, but the seeds are still there,” adds Cheng. “We take the seeds out and give them a protected place to grow. Then when we put them back into the lung, they can grow into mature lung cells to replace the damaged lung tissues in IPF. They can also wake the other seeds up, telling them to help fight the inflammation and ‘improving’ the soil.”

Cheng’s next steps will be to see if potent stem cells can be harvested and grown from biopsied tissues of IPF patients, which would further reduce the number of invasive procedures a patient would need to endure. “We’ve demonstrated that the spheroid is a wonderful method for stem cell production – now we want to try and harvest the original cells during the biopsy,” he says. “Of course, our ultimate goal is to use this method to treat humans with IPF.”

The research appears in STEM CELLS Translational Medicine. The work was supported by the American Heart Association (grant 12BGIA12040477), NC State University’s Chancellor’s Faculty Excellence Program, the NC State Center for Comparative Medicine and Translational Research and the Kenan Foundation Regenerative Medicine Grant. NC State graduate students Eric Henry, Jhon Cores, Taylor Hensley, Shirena Anthony, Tyler Allen, James de Andrade and Adam Vandergriff, as well as Drs. Thomas Caranasos and Jason Lobo from the University of North Carolina at Chapel Hill contributed to the work.


Note to editors:  Abstract follows.

“Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents with Bleomycin-Induced Pulmonary Fibrosis”

Authors: Eric Henry, Jhon Cores, M. Taylor Hensley, Shirena Anthony, Adam Vandergriff, Tyler Allen, James B.M. de Andrade, Ke Cheng, NC State University; Thomas G. Caranasos, L. Jason Lobo, University of North Carolina Chapel Hill
Published: Online in STEM CELLS Translational Medicine

Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have been focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. Here we report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture. Without antigenic sorting, lung spheroids recapitulate stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes.  In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibits apoptosis, fibrosis, and infiltration, but promote angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperforms adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously the spheroid model has only been used to study lung cancer cells. Our data suggest lung spheroids and lung spheroid cells from healthy lung tissues as great sources of regenerative lung cells for therapeutic lung regeneration.

36 responses on “Spheroid Stem Cell Production Sows Hope for IPF Treatment

  1. jitendra selarka says:

    It is very interesting. I like very much. I m suffering from pulmanary fibrosis bronchitis. Now there is no treatment except steirod tab. Pls.intimate further progress.

    1. Danny Faucette says:

      I suffer from IPF and I am very interested in stem cell research and would be willing to participate.

  2. Noel Monjure says:

    Dear Sirs: Very interesting article. I have IPF and approaching 68. We have Celltex here in Texas so I am wondering if I can get a lung tissue biopsy and have this material engineered to MSCs for intravenous therapy? I know human trials are in the future, but I am not waiting.
    Thanks & regards, Noel Monjure

  3. Danny Faucette says:

    I am about and hour from NC State University.

  4. Richard Ledbetter says:

    I have IPF and considering stem cell treatment at the lung institute in Phoenix AR. The article is very encouraging. My brother has the exact same disease.

  5. Lorri Austin says:

    My husband was diagnosed with IPF. Columbia has suggested a lung transplant; doctors at The Lung Institute advised against this. Jim did receive a stem cell treatment early in December but he has not yet noticed an improvement. We are very encouraged by what we are reading though, and would be willing to take part in spheroid stem cell treatment. Please advise.

    1. Sam Dass says:

      Hi Lorri, I am also looking into stem cell for my mum, she will be 75 in Sept and suffering with IPF. How old was your husband when he had stem cell, if you dont mind in sharing please. Kindly share has it made any difference in his quality of life?
      Thanks Sam

  6. Elmer Stobbe says:

    As a recently ipf diagnosed person, I am excited with the research that your team are doing on this dreaded disease. I live in Canada – are any Canadian researcher cooperating with you in these studies, is so, who are they.

  7. Elmer Stobbe says:

    I was recently diagnosed to have ipf. I am excited to hear the progress your team is making using stem cells to regenerate lung tissue. I live in Canada, is your team conducting any rersearch with Canadian scientists’. I would interested to be a participant is such research.

  8. Christa Byars says:

    I have IPF and on a waiting list for lung transplant. I want to learn more about you research. I am 72 years
    old and was diagnosed with IPF two years ago and am
    on oxygen 24/7 now. Considering the Lung Institute for evaluation.

    1. AMIT Sharma says:

      Hi Chris,

      Hv u received any response

  9. AMIT Sharma says:

    My father has been diagnosed with ILD, is this ‘Spheroid stem cell treatment’ is available?, If yes then how can I proceed for it?

    Amit Sharma

  10. tammy martin rivero says:

    I would like to apart of this program. I have an February 22 2916. Thanks. I’m 58 years old.

  11. tammy martin rivero says:

    I’m very interested in the study.

  12. Peggy Rogers says:

    I have recently diagnosed with hypersensitive Pneumonitis at the age 54. I had an accident with fertilizer dust. I had adipose stem cells for the following two years. Last summer, my symptoms started in June. My internist told me that it was pleuracy . I had 2xrays & cat scan done. (Was told cat scan was ok)Returned fo office in October. Internist told me that cat scan wasn’t normal. So I flew out to Arizona for more stem cells in December . The treatment helped to minimize my symptoms . But it only lasted for three months this time i & not like12 months with the first two treatments. I’m planning another stem cell treatment soon. Please keep us up to date on the progress of this lung stem cell proceedure. I live in Atlanta, GA.. I’m a registered nurse too. I will volunteer for this proceedure. Please email me @ pegdarlene @yahoo.com.

  13. Peggy Rogers says:

    I wonder how long for the testing for potent stem cells from IPF patient? Will it be animal or human? If anyone wants to gather a list of names & addresses for volunteer list, I’m game! Send it to my email address in previous comment. I’ll type up a letter & send it to Dr. Cheng.

  14. Bruce LaCoe says:

    I have just been diagnosed with IPF and I am very interested in stem cell research and would be willing to participate in any research studies. I am 65 with no other major ailments.

  15. jack roddey says:

    My husband has an appt in Franklin Tenn Mar 21, 2016 for STEM CELL THERAPY at the LUNG INSTITUTE…..does what you are offering differed from the Lung Institute…..

    Please reply!!!

    Thank you very much!!!

    He has IPF )……(asbestos)

  16. Virginia Corker says:

    My 73 yr old husband diagnosed with IPF Oct 1, 2015. Started Ofev Jan 1. 2016. Would be interested in participating in any Human clinical trial. We live in Mobile, AL.

  17. tammy martin rivero says:

    I want to live,so if can help with research to help others ,i be there for you. Thanks

  18. Monica says:

    Hi, my mother is 51 and was diagnosed with ILD around five years ago. She’s on oxygen all day and would be very happy to take part in trials. Do let us know!

  19. Ron says:

    I would get treatment in Pittsburgh at the Lung Institute but unfortunately,it’s the cost that is stopping me.I would be willing to take part in the research.I will be 79 yrs of age on the 29th of June 2016. God Bless you all.

  20. shelby roddey says:

    I just read an e-mail on this site that I didn’t sent…….I did sent one to the Lung Institute….is that where it was picked up……….from the Lung Institute?????
    Also is this just a research study or can someone go to Chapel Hill and get treatment for SPHERAID LUNG CELLS????..I did have STEM CELL THERAPY in Franklin Tenn on Mar 21, 2016…..so far can not see any change……any help here??????
    Thank you!!

    1. shelby roddey says:

      PS…the treatment was for my husband Jack Roddey……e-mail address in in my name////

  21. Gwenn brainard says:

    My husband has been diagnosed with IPF please let me know if there is a trial with stem cells soon that he could be considered for. Thank you so. Very much

  22. Sarah Jordan says:

    Is there any information on how the study has progressed in the past 2 years and when/if it might be considered for use on humans? Please post an update.

  23. sophia says:

    Sophia William
    I am the daughter of a 58 year old with IPF- It has been the most difficult thing to deal with for myself my dad and my family. As day by day goes by watching my dad suffer hurts more than words can explain….I was so determined to stop this horrible disease…After some years of research online i finally got a solution ,i saw so many positive post online about Good health herbs home,i purchased their herbal remedies for IPF ,my dad used the herbal remedy for 6 weeks and he was totally cured of IPF,my dad is now back to normal life all thanks to good health herbs home.

    1. Mike says:

      I have IPF getting progressively worse. I would be really most interested in knowing the names of the herbs that were successful for your dad, so that I may try them ASAP. Congratulations on finding a solution.
      With thanks

    2. Alam says:

      Please share details of effective herbs. Really valuable information.
      Thanking in advance

  24. Lucy Tanner says:

    I have COPD I am very interested . in this Please let me know every thing you can about it and if there is clinical trials I will participate Thank You

  25. Jason Wilkinson says:

    Hello, when will the phase ONE Clinical Trials start ? I had a talk with Dr Lobo a while ago and he’d mentioned something about Summer.

  26. cecilia anello says:

    Hi I am Cecilia I suffer from pulmonary fibrosis. I am taking the med ofev but its very toxic and very expensive. If it wasn’t for health wellness program I would not be part of this, my salary would not take it. I stem cell program sounds wonderful. good luck on your success and I am very interested to be part of you clinical trails..

  27. cecilia anello says:

    hello, I am Cecilia and I have pulmonary fibrosis. I would like to hear more about your clinical trials on stem cell, and perhaps to participate in the clinical trials. thank you for your time

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