Skip to main content
SpringerLink
Log in
Book cover

Stem Cell Engineering pp 199–211Cite as

Reponses of Mesenchymal Stem Cells to Varying Oxygen Availability In Vitro and In Vivo

  • Chapter
  • First Online:

  • 1091 Accesses

Abstract

Oxygen is vital for cellular metabolism in higher organisms. Explanted somatic cells are regularly cultured at ambient oxygen conditions, which often appear stressful for primary cells, thereby leading to accelerated aging or premature senescence in vitro. Therefore, sophisticated instrumentation for ex vivo cell manipulation has been introduced and is now increasingly being used for the propagation and subsequent differentiation of various types of stem cells. In this particular context also primary mesenchymal stromal cells (MSC) have been investigated. Their developmental fate greatly depends on oxygen availability.

In this contribution, we describe the current knowledge about MSC properties according to varying oxygen tension in vitro: while reduced oxygen tension supports their proliferation, differentiation potential is reversibly attenuated. This finding is relevant for various in vivo situations such as wound healing or distinct pathologic alterations. Inappropriate oxygenation is actually not impacting on MSC viability, but greatly diminishes their differentiation capabilities, in due course leading to irreversible changes in tissue structure including functional alterations involved.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A. Clarification of the nomenclature for MSC: the international society for cellular therapy position statement. Cytotherapy. 2005; 7:393–395.

    Article  Google Scholar 

  2. Watt FM, Hogan BL. Out of Eden: stem cells and their niches. Science. 2000; 287:1427–1430.

    Article  Google Scholar 

  3. Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991; 9:641–650.

    Article  Google Scholar 

  4. Barry FP, Murphy JM. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol. 2004; 36:568–584.

    Article  Google Scholar 

  5. Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum. 2005; 52:2521–2529.

    Article  Google Scholar 

  6. Muguruma Y, Yahata T, Miyatake H, Sato T, Uno T, Itoh J, Kato S, Ito M, Hotta T, Ando K. Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment. Blood. 2005; 107: 1878–1887.

    Article  Google Scholar 

  7. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997; 276:71–74.

    Article  Google Scholar 

  8. Dorshkind K. Regulation of hemopoiesis by bone marrow stromal cells and their products. Annu Rev Immunol. 1990; 8:111–137.

    Article  Google Scholar 

  9. Fehrer C, Lepperdinger G. Mesenchymal stem cell aging. Exp Gerontol. 2005; 40:926–930.

    Article  Google Scholar 

  10. Sethe S, Scutt A, Stolzing A. Aging of mesenchymal stem cells. Ageing Res Rev. 2006; 5:91–116.

    Article  Google Scholar 

  11. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284:143–147.

    Article  Google Scholar 

  12. Prockop DJ, Sekiya I, Colter DC. Isolation and characterization of rapidly self-renewing stem cells from cultures of human marrow stromal cells. Cytotherapy. 2001; 3:393–396.

    Article  Google Scholar 

  13. Simmons PJ, Torok-Storb B. Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood. 1991; 78:55–62.

    Google Scholar 

  14. Horwitz EM, Keating A. Nonhematopoietic mesenchymal stem cells: what are they? Cytotherapy. 2000; 2:387–388.

    Article  Google Scholar 

  15. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8:315–317.

    Article  Google Scholar 

  16. Ishikawa Y, Ito T. Kinetics of hemopoietic stem cells in a hypoxic culture. Eur J Haematol. 1988; 40:126–129.

    Article  Google Scholar 

  17. Antoniou ES, Sund S, Homsi EN, Challenger LF, Rameshwar P. A theoretical simulation of hematopoietic stem cells during oxygen fluctuations: prediction of bone marrow responses during hemorrhagic shock. Shock. 2004; 22:415–422.

    Article  Google Scholar 

  18. Chow DC, Wenning LA, Miller WM, Papoutsakis ET. Modeling pO(2) distributions in the bone marrow hematopoietic compartment. I. Krogh’s model. Biophys J. 2001; 81:675–684.

    Article  Google Scholar 

  19. Cooper PD, Burt AM, Wilson JN. Critical effect of oxygen tension on rate of growth of animal cells in continuous suspended culture. Nature. 1958; 182:1508–1509.

    Article  Google Scholar 

  20. Packer L, Fuehr K. Low oxygen concentration extends the lifespan of cultured human diploid cells. Nature. 1977; 267:423–425.

    Article  Google Scholar 

  21. Zwartouw HT, Westwood JC. Factors affecting growth and glycolysis in tissue culture. Br J Exp Pathol. 1958; 39:529–539.

    Google Scholar 

  22. Ankeny DP, McTigue DM, Jakeman LB. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol. 2004; 190:17–31.

    Article  Google Scholar 

  23. Cui JH, Park K, Park SR, Min BH. Effects of low-intensity ultrasound on chondrogenic differentiation of mesenchymal stem cells embedded in polyglycolic acid-an in vivo study. Tissue Eng. 2006; 12:75–82.

    Article  Google Scholar 

  24. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425:841–846.

    Article  Google Scholar 

  25. Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, Ross J, Haug J, Johnson T, Feng JQ, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003; 425:836–841.

    Article  Google Scholar 

  26. Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, Abramova N, Vincent P, Pumiglia K, Temple S. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science. 2004; 304:1338–1340.

    Article  Google Scholar 

  27. Cotsarelis G, Sun TT, Lavker RM. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 1990; 61:1329–1337.

    Article  Google Scholar 

  28. Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008; 3:301–313.

    Article  Google Scholar 

  29. da Silva Meirelles L, Caplan AI, Nardi NB. In search of the in vivo identity of mesenchymal stem cells. Stem Cells. 2008; 26:2287–2299.

    Article  Google Scholar 

  30. Jauniaux E, Watson A, Ozturk O, Quick D, Burton G. In-vivo measurement of intrauterine gases and acid-base values early in human pregnancy. Hum Reprod. 1999; 14:2901–2904.

    Article  Google Scholar 

  31. Heppenstall RB, Grislis G, Hunt TK. Tissue gas tensions and oxygen consumption in healing bone defects. Clin Orthop Relat Res. 1975; 106:357–365.

    Article  Google Scholar 

  32. Knighton DR, Silver IA, Hunt TK. Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration. Surgery. 1981; 90:262–270.

    Google Scholar 

  33. Fehrer C, Brunauer R, Laschober G, Unterluggauer H, Reitinger S, Kloss F, Gully C, Gassner R, Lepperdinger G. Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan. Aging Cell. 2007; 6:745–757.

    Article  Google Scholar 

  34. Studer G, Gratz KW, Glanzmann C. Osteoradionecrosis of the mandibula in patients treated with different fractionations. Strahlenther Onkol. 2004; 180:233–240.

    Article  Google Scholar 

  35. Grünert J, Kloss D, Kloss F. Strahlenschäden. In: Krupp S, Rennekampff HO, ed. Plastische Chirurgie. Berlin: Ecomed Verlag; 2004, pp. 1–16.

    Google Scholar 

  36. Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg. 1983b; 41:283–288.

    Article  Google Scholar 

  37. Marx RE. A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg. 1983a; 41:351–357.

    Article  Google Scholar 

  38. Bras J, de Jonge HK, van Merkesteyn JP. Osteoradionecrosis of the mandible: pathogenesis. Am J Otolaryngol. 1990; 11:244–250.

    Article  Google Scholar 

  39. Redpath JL, Gutierrez M. Kinetics of induction of reactive oxygen species during the post-irradiation expression of neoplastic transformation in vitro. Int J Radiat Biol. 2001; 77: 1081–1085.

    Article  Google Scholar 

  40. Koc ON, Peters C, Aubourg P, Raghavan S, Dyhouse S, DeGasperi R, Kolodny EH, Yoseph YB, Gerson SL, Lazarus HM, et al. Bone marrow-derived mesenchymal stem cells remain host-derived despite successful hematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases. Exp Hematol. 1999; 27:1675–1681.

    Article  Google Scholar 

  41. Hasse A, Porksen M, Schultze S, Engel A, Feyerabend T. Effect of bFGF on regeneration of distracted mandibles after radiation. Mund Kiefer Gesichtschir. 2000; 4(Suppl 2):S423–S427.

    Article  Google Scholar 

  42. Wurzler KK, DeWeese TL, Sebald W, Reddi AH. Radiation-induced impairment of bone healing can be overcome by recombinant human bone morphogenetic protein-2. J Craniofac Surg. 1998; 9:131–137.

    Article  Google Scholar 

  43. Bertho JM, Mathieu E, Lauby A, Frick J, Demarquay C, Gourmelon P, Gorin NC, Thierry D. Feasibility and limits of bone marrow mononuclear cell expansion following irradiation. Int J Radiat Biol. 2004; 80:73–81.

    Article  Google Scholar 

  44. Chen MF, Lin CT, Chen WC, Yang CT, Chen CC, Liao SK, Liu JM, Lu CH, Lee KD. The sensitivity of human mesenchymal stem cells to ionizing radiation. Int J Radiat Oncol Biol Phys. 2006; 66:244–253.

    Article  Google Scholar 

  45. Schonmeyr BH, Wong AK, Soares M, Fernandez J, Clavin N, Mehrara BJ. Ionizing radiation of mesenchymal stem cells results in diminution of the precursor pool and limits potential for multilineage differentiation. Plast Reconstr Surg. 2008; 122:64–76.

    Article  Google Scholar 

  46. Li J, Kwong DL, Chan GC. The effects of various irradiation doses on the growth and differentiation of marrow-derived human mesenchymal stromal cells. Pediatr Transplant. 2007; 11:379–387.

    Article  Google Scholar 

  47. Dickhut A, Schwerdtfeger R, Kuklick L, Ritter M, Thiede C, Neubauer A, Brendel C. Mesenchymal stem cells obtained after bone marrow transplantation or peripheral blood stem cell transplantation originate from host tissue. Ann Hematol. 2005; 84:722–727.

    Article  Google Scholar 

  48. Francois S, Bensidhoum M, Mouiseddine M, Mazurier C, Allenet B, Semont A, Frick J, Sache A, Bouchet S, Thierry D, et al. Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage. Stem Cells. 2006; 24:1020–1029.

    Article  Google Scholar 

  49. Klopp AH, Spaeth EL, Dembinski JL, Woodward WA, Munshi A, Meyn RE, Cox JD, Andreeff M, Marini FC. Tumor irradiation increases the recruitment of circulating mesenchymal stem cells into the tumor microenvironment. Cancer Res. 2007; 67:11687–11695.

    Article  Google Scholar 

Download references

Acknowledgments

The authors are grateful for sustained collaboration with, as well as guidance and supervision during their clinical research by, Dr. Robert Gaßner. GL’s work is supported by the Austrian Science Fund (FWF), NRN project S9305, and by the Austrian Research Agency (FFG). The authors greatly acknowledge the support by the Jubilee Fund of the Austrian National Bank (OeNB).

Author information

Authors and Affiliations

  1. Department of Cranio-Maxillofacial and Oral Surgery, University Hospital Innsbruck, Innsbruck, Austria

    Frank R. Kloss & Sarvpreet Singh

  2. Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria

    Sarvpreet Singh & Günter Lepperdinger

Authors
  1. Frank R. Kloss
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarvpreet Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Günter Lepperdinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Günter Lepperdinger .

Editor information

Editors and Affiliations

  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

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Kloss, F.R., Singh, S., Lepperdinger, G. (2011). Reponses of Mesenchymal Stem Cells to Varying Oxygen Availability In Vitro and In Vivo. In: Artmann, G., Minger, S., Hescheler, J. (eds) Stem Cell Engineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-11865-4_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-11865-4_9

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-11864-7

  • Online ISBN: 978-3-642-11865-4

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation