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The Potential of Selectively Cultured Adult Stem Cells Re-implanted in Tissues

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Stem Cell Engineering

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Abstract

For stem cell research the focus in the past has been on embryonic stem cells, cells from which humans are initially constructed, but which are limited in availability. A new direction in stem cell research is looking at a different kind of pluripotent cells – adult stem cells, which are responsible for maintenance and repair of tissue. To retrieve and grow stem cells remains an important challenge in medicine, but carries the hope to cure many diseases. Pluripotent adult stem cells have been found in many organs and also in cancer tumors. Adult stem cells can both self-renew and differentiate to replace compromised tissue in the organ where they reside. If single adult tumor stem cells can re-grow into a new tumor, just as adult stem cells can rebuild a physiological organ, the potential of adult stem cells would be significant in new cancer therapy and organ engineering approaches.

This chapter introduces the methods behind isolation of adult stem cells, in vitro culturing, characterization, genetic manipulation for imaging purposes, and the promising results of re-implantation into healthy tissues. Adult stem cells derived from human early-stage prostate tumors are used in a newly developed, novel research model. Since the environmental niche is an important factor for stem cell growth ex vivo, stem cell isolation is achieved via culturing in a characterized environment that mimics the stem cell niche for these types of adult stem cells. The human prostate tumor stem cell niche is described and prostate tumor stem cells (PrTuSCs) are used to show the so-called stem cell center (SCC) growth in cell culture. It is also demonstrated how PrTuSCs are epigenetically altered with eGFP for tracking and imaging purposes. Cultured PrTuSCs are characterized as adult stem cells by stem cell marker analysis and expression of stem cell-associated transcription factors. To further demonstrate the pluripotent potential of PrTuSC, the effects of re-implantation into healthy tissues in vivo are presented in the orthotopic xenografting and tissue recombination methods. When implanted into immune-suppressed SCID mice, results show that cultured PrTuSC not only can re-grow a cancerous prostate tumor, but, depending on the implantation site and its microenvironment, also have the ability to generate normal benign human prostate glandular structures in vivo. The dorsal mouse-skinfold window chamber method is introduced as an experimental model that allows direct observation of implanted stem cells and their behavioral characteristics, e.g., promotion of healthy or tumor-associated angiogenesis, which is critical in tissue renewal and cancer metastasis.

Clinical applications in the near future might include short-term SCC-colony counts as an in vitro surrogate method that shows capability of predicting the probability of tumor re-occurrence and progression. Finally, it is discussed that methodologies similar to this may be used to derive human tumor stem cells from biopsies or from surgical specimens of other human epithelial tumor sources, e.g., breast, colorectal, liver, and others. Using adult stem cell models will provide many future applications in medicine covering new strategies in cancer diagnosis and treatment as well as promising regenerative tissue and organ reconstruction approaches.

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Authors and Affiliations

  1. Department of Bioengineering and School of Medicine, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA

    Isgard S. Hueck

  2. Department of Mechanical and Aerospace Engineering, Division of Biology and Material Science, and School of Medicine, Cancer Center, University of California San Diego, La Jolla, CA, USA

    Martin Haas

  3. Department of Mechanical and Aerospace Engineering, Division of Biology and Material Science, University of California San Diego, La Jolla, CA, USA

    Rita Finones

  4. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA

    Jane Frimodig & David A. Gough

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  1. Isgard S. Hueck
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  2. Martin Haas
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  3. Rita Finones
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  4. Jane Frimodig
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  5. David A. Gough
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  1. FH Aachen, Standort Jülich, Ginsterweg 1, Jülich, 52428, Germany

    Gerhard M. Artmann

  2. Wolfson Centre for Age-Related Diseases, GKT School of Biomedical Sciences, King's College London, London, SE11UL, United Kingdom

    Stephen Minger

  3. Inst. Neurophysiologie, Universitätsklinikum Köln, Robert-Koch-Str. 39, Köln, 50931, Germany

    Jürgen Hescheler

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Hueck, I.S., Haas, M., Finones, R., Frimodig, J., Gough, D.A. (2011). The Potential of Selectively Cultured Adult Stem Cells Re-implanted in Tissues. In: Artmann, G., Minger, S., Hescheler, J. (eds) Stem Cell Engineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-11865-4_4

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