Exciting Treatment Possibilities with Stem Cells; What is the Best Cell Culture Method?

By on February 21, 2012

Brandy Sargent, Editor, The Cell Culture Dish

Researchers at Memorial Hermann-Texas Medical Center are working towards using umbilical cord blood stem cell transplants to limit or reverse hearing loss in infants. They have been able to confirm that stem cells inserted into the ears of mice helped rebuild their inner ear structure and they are betting that the same can be done with human infants. Another study conducted by the University of Texas, Health Science Center at Houston (UT Health) and published in the journal Neurosurgery examined the use of stem cells to treat traumatic brain injury (TBI) in pediatric patients. TBI is one of the leading causes of death in children and those that survive often have serious disabilities. There are currently no treatments available to repair a child’s damaged brain. In Phase I of the study, designed to look at safety, 10 children between the ages of 5-14 years received stem cells obtained from the patient’s bone marrow. After six months of monitoring, the treatment was deemed safe and all children showed improvement, 7 children had only a mild disability or none at all. In addition to these two applications stem cells are also being tested to treat several other childhood diseases including: cerebral palsy, juvenile diabetes and childhood leukemia.

One of the problems with stem cell applications is obtaining a sufficient quantity of stem cells for therapeutic application. One approach is to expand the stem cells using cell culture techniques. Stem cell expansion prior to application may play an even larger role given that it has been recently determined that the majority of privately banked cord blood samples have an inadequate number of stem cells for direct therapeutic application. Please see the Stem Cell Assay Blog titled “Analysis of the Quality of Autologous Cord Blood Stored in Private Banks.”

Stem cells have so much potential, and with so many new treatments on the horizon the question is often raised – what is the method to culture and expand these cells for therapeutic use. Frequently stem cells are cultured using serum, knock out serum replacement or other animal origin ingredients such as bovine albumin, bovine transferrin or human blood derived albumin or transferrin. Although it is better to use albumin and transferrin or knock out serum replacement products, these still carry the risk of adventitious infectious agents from animal origin and they also have the variability of performance typically seen with these types of ingredients. When these cells are being used for therapeutic use it is desirable to remove all animal and all human blood derived products. This is both a safety and a regulatory advantage because it greatly reduces the risk of viral or prion contamination.

A recent study by Paul Price, Ph.D. (ThermoFisher Scientific) and Steve Pettit, Ph.D. (InVitria) and others suggests that it is not only possible to grow these cells in a serum-free and animal free culture media, but that they can thrive in this environment without the need for blood components or knock out serum replacement. The study was conducted using CD34+ hematopoietic stem cells isolated from human umbilical cord blood. The expansion of these cells was evaluated in an animal-free and xeno-free Hematopoietic Stem Cell Expansion (HPE-) Medium (D-Finitive Cell Technologies, now part of ThermoFisher), which contained recombinant human albumin and recombinant human transferrin. The study shows that the recombinant versions of these proteins improved the expansion and growth of stem cells compared to the animal-derived versions. About the study, Dr. Price said “When evaluating various protein supplements for the expansion of both human mononuclear and hematopoietic stem cells, I found that a combination of InVitria’s Cellastim and Optiferrin significantly outperformed the best non-recombinant proteins. It’s clear to me that these recombinant components can enable the development of superior animal-free expansion media for stem cell applications.”

Please click here to view the study titled “Recombinant Transferrin and Albumin Improves Mononuclear and Hematopoietic Stem Cell Expansion.”

The media companies who have developed animal-free or xeno-free stem cell media and media supplements. Some product examples include

The development of new media solutions that are not only serum free, but also animal component free will lead to scalable and commercially viable clinical manufacturing of stem cell therapies.

Have you tried these media solutions? We would be interested in in hearing from you about your results. Please contact the Editor.

8 Comments

  1. Jim H

    21 February, 2012 at 2:10 PM

    But are HSC anchorage dependent? Hollow Fiber Bioreactors have been around for years. Why aren’t people using them instead of plastic dishes? http://www.fibercellsystems.com/ My placental cell lines grow for at least 3 months in this system. I am looking for HSC progenitors in these populations, since the placenta is the source of hematopoeisis for the developing fetus.

    • The Dish

      22 February, 2012 at 10:09 AM

      I know that there are bioreactors that are in use to enable cell expansion. Some bioreactors are proprietary and are crucial to the success of manufacturing certain stem cell therapies.

      Two companies that I know use 3D bioreactors for cell expansion are Pluristem and Advanced BioHealing.
      Pluristem uses proprietary 3D bioreactors for their stem cells. An illustration is on their website. http://pluristem.com/index.php?option=com_content&view=article&id=7&Itemid=41

      Advanced BioHealing uses roller bottles, then bioreactors in the fibroblast expansion for their Dermagraft product. There is a video on their website that describes the process. http://www.abh.com/product/product-videos/#manufacturing

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  3. Michael An

    25 February, 2012 at 7:27 PM

    Hi Brandy,
    Nice article. We at StemRD have also developed serum-free/xeno-free media for stem cells (human MSC and iPSC/ESC). Your readers might be interested in these products at weblinks:
    MesenGro: http://www.stemrd.com/index.php?/Media/MesenGro-%C2%AE/flypage.tpl.html
    PSGro: https://www.stemrd.com/index.php?/Media/PSGro-Medium/flypage.tpl.html

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