Stem Cells – the future of regenerative medicine and cell therapy

Provide an animal free, clean and flexible 3D environment for your stem cells, allowing you to take complete control.

 

With GrowDex, you can kickstart your stem cell cultures and research with a flexible 3D system, gaining complete control over your 3D stem cell culture environment, while directing cell fate as you wish.

  • Expand and differentiate your stem cells with high yield and full control of the environment for regenerative medicine and cell therapy applications.
    • GrowDex hydrogels are made of only nanocellulose and water. This makes it possible to take full control, what you are adding to the culture system.
  • Flexibility to study cellular organization, cell-to-cell and cell-to-matrix interactions.
    • Tune the stiffness, link molecules (GF, ECM proteins etc.) and study how drug molecules interact with your cells.
    • Small drug molecules (≤1 kDa) and large molecules (e.g. antibodies – 150 kDa) diffuse through GrowDex hydrogels as it contains only a small amount of nanocellulose fibres and mainly water.
    • Make complex organoid or co-culture models by combining multiple cell types in the 3D environment.
  • More physiologically relevant morphology, gene expression and biological response.
    • Characterize your cells by observing cellular morphology during culture or by staining your cells. GrowDex hydrogels have great imaging properties and reagents diffuse through the matrix.
    • Recover your cells with GrowDase™ cellulase enzyme without affecting them to study gene- or protein expression.
 

Animal free*

Clean and well-defined hydrogels consisting of only nanofibrillar cellulose and purified water. No animal DNA interfering with readouts.

Tunability

Tune the microenvironment to suit your cells. The optimal stiffness is achieved by dilution with cell culture medium, and the culturing matrix can be customized easily by simply adding components such as growth factors or proteins directly to the gel.

Microscope and high throughput compatible

GrowDex hydrogels do not have auto-fluorescence so imaging with any microscope or high content imaging system is simple.The ambient handling of the hydrogels makes them ideal for high throughput assays.

One-step cell recovery

Cells and organoids can be recovered from GrowDex with a gentle one-step enzymatic process with our GrowDase without affecting the cells.

 

What can stem cells do?

Stem cells have become the highlight of biomedical research, regenerative medicine, disease modelling and even the food industry. Great progress has been made over the last 60 years, from the first bone marrow transplantation between twins in 1959 [1], through to recent engineered stem cells using CRISPR for clinical trials as a ‘Trojan Horse’, delivering oncolytic virus to target cancers [2].  

Stem cells are being used in disease models [3] and to develop novel drug treatments for diseases, such as aberrant musculoskeletal development and resistance to cancer in down syndrome [4]. Even stem cell derived products, such as extracellular vesicles and paracrine factors are being harnessed as therapeutic products, such as protective paracrine factors for cardiomyocytes taken from cardiac mesenchymal stromal cells [5].

An interesting new area for stem cell research has raised from a very daily topic to all of us, food. The tissue engineering and regenerative medicine techniques are now also used to study in vitro culture of meat. The focus of lab generated meat, is to culture stem cells harvested from muscle and fat, expand them and combine with a biomaterial to finally differentiate and mix them to become a desired meat product.

To unleash the full potential of stem cells, there is still a lot of work required to provide them as an 'off the shelf' product.

Why change from 2D to 3D now?

In vitro culture expansion of stem cells is a necessary but costly step in 2D, to get enough cells for the intended therapeutic application.  Extraction of the stem cells from their endogenous niche and 2D in vitro culture expansion can lead to accumulation of chromosomal aberrations while prolonged 2D cultivation has been reported to lead to a loss of multipotency and premature cellular senescence in MSCs [6-8]. 3D cell cultures produce more in vivo-like multicellular structures such as spheroids which cannot be obtained in 2D.

To be or not to be animal free?

Animal derived cells (such as OP9 feeder layer cells) and extra cellular matrix molecules (such as Matrigel and collagen) have been widely used for the culture of stem cells. However, these have been notoriously difficult to use due to lot-to-lot variability [9], complex and unknown protein composition [10] as well as inhibiting the translation of the cell culture system towards clinical application. There is a clear need for a well-defined tuneable scaffold ensuring consistent growth, differentiation and translatability for downstream applications.

Gain complete control over your stem cell culture.

It is important to consider the effect of the extracellular matrix and microenvironment on your cells or cellular derived products. If you are working with ESCs, iPSCs, MSCs or other stem cells, GrowDex® hydrogels can provide you with a 3D microenvironment to best suit your purposes.

GrowDex has been used for many different applications with stem cells, from culture expanding ESCs and iPSCs through to the use as a stem cell niche for the inner ear (see figure 1 below). The nanofibrillar cellulose provides structural support for cells allowing them to migrate through the gel, form spheroids or develop into complex organoids. Since there are no growth factors or other molecules within GrowDex, you have complete control over what is provided to your cells.

Related Publications:

  • Chang, H.-T., et al. (2020) An engineered three-dimensional stem cell niche in the inner ear by applying a nanofibrillar cellulose hydrogel with a sustained-release neurotrophic factor delivery system. Acta Biomaterialia 108: p. 111-127. https://www.sciencedirect.com/science/article/abs/pii/S1742706120301392?via%3Dihub
  • Kiiskinen J. et al. (2019) Nanofibrillar cellulose wound dressing supports the growth and characteristics of human mesenchymal stem/stromal cells without cell adhesion coatings. Stem Cell Research & Therapy 2019, 10:292. https://doi.org/10.1186/s13287-019-1394-7
  • Harjumäki R. et al. (2019) Quantified forces between HepG2 hepatocarcinoma and WA07 pluripotent stem cells with natural biomaterials correlate with in vitro cell behavior. Scientific Reports 2019; 9, 7354. https://doi.org/10.1038/s41598-019-43669-7
  • Sheard J et al. (2019) Optically Transparent Anionic Nanofibrillar Cellulose Is Cytocompatible with Human Adipose Tissue-Derived Stem Cells and Allows Simple Imaging in 3D. Stem Cells International. In press. https://doi.org/10.1155/2019/3106929
  • Azoidis, J. Metcalfe, J. Reynolds, S. Keeton, S. Hakki, J. Sheard and D. Widera (2017). Three-dimensional cell culture of human mesenchymal stem cells in nanofibrillar cellulose hydrogels. MRS Communications, p. 1-8. https://doi.org/10.1557/mrc.2017.59
  • Yan-Ru Lou, Liisa Kanninen, Bryan Kaehr, Jason L. Townson, Johanna Niklander, Riina Harjumäki, C. Jeffrey Brinker & Marjo Yliperttula (2015). Silica bioreplication preserves three-dimensional spheroid structures of human pluripotent stem cells and HepG2 cells. Nature Scientific Reports 5:13635 https://doi.org/10.1038/srep13635
  • Yan-Ru Lou, Liisa Kanninen, Tytti Kuisma, Johanna Niklander, Luke A. Noon, Deborah Burks, Arto Urtti and Marjo Yliperttula (2014). The Use of Nanofibrillar Cellulose Hydrogel as a Flexible Three-Dimensional Model to Culture Human Pluripotent Stem Cells. Stem Cells and Development, Volume 23, Number 4. https://www.ncbi.nlm.nih.gov/pubmed/24188453

 Related Application Notes:

 

 

Publications referenced here:

  1. Thomas, E.D., et al. (1959). "Supralethal Whole Body Irradiation And Isologous Marrow Transplantation in Man." The Journal of Clinical Investigation 38(10): p. 1709-1716.
  2. von Einem, J.C., et al. (2017). "Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells - TREAT-ME-1 - a phase I, first in human, first in class trial." Oncotarget 8(46): p. 80156-80166.
  3. Galat, Y., et al. (2020). "iPSC-derived progenitor stromal cells provide new insights into aberrant musculoskeletal development and resistance to cancer in down syndrome." Scientific Reports 10(1): p. 13252.
  4. Kimbrel, E.A. and Lanza, R. (2020). "Next-generation stem cells — ushering in a new era of cell-based therapies." Nature Reviews Drug Discovery 19(7): p. 463-479.
  5. Southam, A.D., et al. (2015). "Drug Redeployment to Kill Leukemia and Lymphoma Cells by Disrupting SCD1-Mediated Synthesis of Monounsaturated Fatty Acids." Cancer Research 75(12): p. 2530-2540.
  6. Bara, J.J., et al. (2014). "Concise review: Bone marrow-derived mesenchymal stem cells change phenotype following in vitro culture: implications for basic research and the clinic." Stem Cells 32(7): p. 1713-23.
  7. Ben-David, U., et al. (2011). "Large-Scale Analysis Reveals Acquisition of Lineage-Specific Chromosomal Aberrations in Human Adult Stem Cells." Cell Stem Cell 9(2): p. 97-102.
  8. Turinetto, V., et al. (2016). "Senescence in Human Mesenchymal Stem Cells: Functional Changes and Implications in Stem Cell-Based Therapy." Int J Mol Sci 17(7).
  9. Patel, R. and Alahmad, A.J. (2016). "Growth-factor reduced Matrigel source influences stem cell derived brain microvascular endothelial cell barrier properties." Fluids and Barriers of the CNS 13(1): p. 6.
  10. Hughes, C.S., et al. (2010). "Matrigel: A complex protein mixture required for optimal growth of cell culture." PROTEOMICS 10(9): p. 1886-1890.
  11. Lou, Y.-R., et al. (2014). "The Use of Nanofibrillar Cellulose Hydrogel As a Flexible Three-Dimensional Model to Culture Human Pluripotent Stem Cells." Stem Cells and Development 23(4): p. 380-392.
  12. Chang, H.-T., et al. (2020). "An engineered three-dimensional stem cell niche in the inner ear by applying a nanofibrillar cellulose hydrogel with a sustained-release neurotrophic factor delivery system." Acta Biomaterialia 108: p. 111-127.
  13. Sheard, J. "Adipose derived mesenchymal stem cells: Investigating sphere formation in relation to seeding density and hydrogel concentration." GrowDex Application Note 22.
  14. Sheard, J.J., et al. (2019). "Optically Transparent Anionic Nanofibrillar Cellulose Is Cytocompatible with Human Adipose Tissue-Derived Stem Cells and Allows Simple Imaging in 3D." Stem Cells International 2019: p. 12.

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