Skip to main content
SpringerLink
Log in

Hematopoietic stem cells: multiparameter regulation

  • Review Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Hematopoietic stem cells (HSCs) are capable to self-renew with multi-potency which generated much excitement in clinical therapy. However, the main obstacle of HSCs in clinical application was insufficient number of HSCs which were derived from either bone marrow, peripheral blood or umbilical cord blood. This review briefly discusses the indispensable utility of growth factors and cytokines, stromal cells, extracellular matrix, bionic scaffold and microenvironment aiming to control the hematopoiesis in all directions and provide a better and comprehensive understanding for in vitro expansion of hematopoietic stem cells.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Boitano AE, Wang J, Romeo R, Bouchez LC, Parker AE, Sutton SE, et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science. 2010;329:1345–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466:829–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jackson KA, Majka SM, Wulf GG, Goodell MA. Stem cells: a minireview. J Cell Biochem. 2002;85:1–6.

    Article  Google Scholar 

  4. Pazianos G, Uqoezwa M, Reya T. The elements of stem cell self-renewal: a genetic perspective. Biotechniques. 2003;35:1240–7.

    CAS  PubMed  Google Scholar 

  5. Anne Wilson EL, Trumpp Andreas. Balancing dormant and self-renewing hematopoietic stem cells. Curr Opin Genet Dev. 2009;19:461–8.

    Article  PubMed  Google Scholar 

  6. Lapidot T, Petit I. Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol. 2002;30:973–81.

    Article  CAS  PubMed  Google Scholar 

  7. Anasetti C, Beatty PG, Storb R, Martin PJ, Mori M, Sanders JE, et al. Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. Hum Immunol. 1990;29:79–91.

    Article  CAS  PubMed  Google Scholar 

  8. Davies S, Shu X, Blazar B, Filipovich A, Kersey J, Krivit W, et al. Unrelated donor bone marrow transplantation: influence of HLA A and B incompatibility on outcome. Blood. 1995;86:1636–42.

    CAS  PubMed  Google Scholar 

  9. Gluckman E. Current status of umbilical cord blood hematopoietic stem cell transplantation. Exp Hematol. 2000;28:1197–205.

    Article  CAS  PubMed  Google Scholar 

  10. Wagner JE, Rosenthal J, Sweetman R, Shu XO, Davies SM, Ramsay N, et al. Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. Blood. 1996;88:795–802.

    CAS  PubMed  Google Scholar 

  11. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C, et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood. 2002;100:1611–8.

    CAS  PubMed  Google Scholar 

  12. Koestenbauer S, Zisch A, Dohr G, Zech NH. Protocols for hematopoietic stem cell expansion from umbilical cord blood. Cell Transplant. 2009;18:1059–68.

    Article  PubMed  Google Scholar 

  13. Lataillade J-J, Clay D, Dupuy C, Rigal S, Jasmin C, Bourin P, et al. Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival. Blood. 2000;95:756–68.

    CAS  PubMed  Google Scholar 

  14. Yeoh JS, van Os R, Weersing E, Ausema A, Dontje B, Vellenga E, et al. Fibroblast growth factor-1 and -2 preserve long-term repopulating ability of hematopoietic stem cells in serum-free cultures. Stem Cells. 2006;24:1564–72.

    Article  CAS  PubMed  Google Scholar 

  15. Sugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12–CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006;25:977–88.

    Article  CAS  PubMed  Google Scholar 

  16. De Angeli S, Baiguera S, Del Pup L, Pavan E, Gajo G, Di Liddo R, et al. Middle-term expansion of hematopoietic cord blood cells with new human stromal cell line feeder-layers and different cytokine cocktails. Int J Mol Med. 2009;24:837–45.

    Article  PubMed  Google Scholar 

  17. Wagner W, Horn P, Bork S, Ho AD. Aging of hematopoietic stem cells is regulated by the stem cell niche. Exp Gerontol. 2008;43:974–80.

    Article  CAS  PubMed  Google Scholar 

  18. Renström J, Kröger M, Peschel C, Oostendorp RA. How the niche regulates hematopoietic stem cells. Chem Biol Interact. 2010;184:7–15.

    Article  PubMed  Google Scholar 

  19. Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014;505:327–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lui WC, Chan YF, Chan LC, Ng RK. Cytokine combinations on the potential for ex vivo expansion of murine hematopoietic stem cells. Cytokine. 2014;68:127–32.

    Article  CAS  PubMed  Google Scholar 

  21. Mayack SR, Wagers AJ. Osteolineage niche cells initiate hematopoietic stem cell mobilization. Blood. 2008;112:519–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bernardo ME, Fibbe WE. Mesenchymal stromal cells and hematopoietic stem cell transplantation. Immunol Lett. 2015;168:215–21.

    Article  CAS  PubMed  Google Scholar 

  23. Fan X, Gay FPH, Ong S-Y, Ang JML, Chu PPY, Bari S, et al. Mesenchymal stromal cell supported umbilical cord blood ex vivo expansion enhances regulatory T cells and reduces graft versus host disease. Cytotherapy. 2013;15:610–9.

    Article  CAS  PubMed  Google Scholar 

  24. Schultz JS, Naumov IM, Vecchini F, Boggs SS, Virji MA. Enhancement of cell production in long-term bone marrow culture. Int J Cell Cloning. 1992;10:161–5.

    Article  CAS  PubMed  Google Scholar 

  25. Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, MacArthur BD, Lira SA, Scadden DT, Maayan A, Enikolopov GN, Frenette PS. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466:829–34.

    Article  PubMed  PubMed Central  Google Scholar 

  26. da Silva CL, Gonçalves R, Crapnell KB, Cabral JM, Zanjani ED, Almeida-Porada G. A human stromal-based serum-free culture system supports the ex vivo expansion/maintenance of bone marrow and cord blood hematopoietic stem/progenitor cells. Exp Hematol. 2005;33:828–35.

    Article  PubMed  Google Scholar 

  27. Breems DA, Blokland EA, Siebel KE, Mayen AE, Engels LJ, Ploemacher RE. Stroma-contact prevents loss of hematopoietic stem cell quality during ex vivo expansion of CD34+ mobilized peripheral blood stem cells. Blood. 1998;91:111–7.

    CAS  PubMed  Google Scholar 

  28. Oostendorp RA, Robin C, Steinhoff C, Marz S, Bräuer R, Nuber UA, et al. Long-term maintenance of hematopoietic stem cells does not require contact with embryo-derived stromal cells in cocultures. Stem Cells. 2005;23:842–51.

    Article  CAS  PubMed  Google Scholar 

  29. Szaryńska M, Myśliwski A, Myśliwska J, Kmieć Z, Preis K, Zabul P. Cytokine profiles during delivery affect cord blood hematopoietic stem and progenitors cells. Cell Immunol. 2015;293:137–41.

    Article  PubMed  Google Scholar 

  30. Fox N, Priestley G, Papayannopoulou T, Kaushansky K. Thrombopoietin expands hematopoietic stem cells after transplantation. J Clin Invest. 2002;110:389–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Qian H, Buza-Vidas N, Hyland CD, Jensen CT, Antonchuk J, Mansson R, et al. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell. 2007;1:671–84.

    Article  CAS  PubMed  Google Scholar 

  32. Sitnicka E, Ruscetti F, Priestley G, Wolf N, Bartelmez S. Transforming growth factor beta 1 directly and reversibly inhibits the initial cell divisions of long-term repopulating hematopoietic stem cells. Blood. 1996;88:82–8.

    CAS  PubMed  Google Scholar 

  33. Sensebe L, Deschaseaux M, Li J, Herve P, Charbord P. The broad spectrum of cytokine gene expression by myoid cells from the human marrow microenvironment. Stem Cells. 1997;15:133–43.

    Article  CAS  PubMed  Google Scholar 

  34. Mbalaviele G, Jaiswal N, Meng A, Cheng L, Van Den Bos C, Thiede M. Human mesenchymal stem cells promote human osteoclast differentiation from CD34+ bone marrow hematopoietic progenitors 1. Endocrinology. 1999;140:3736–43.

    CAS  PubMed  Google Scholar 

  35. Shyu W-C, Lin S-Z, Yang H-I, Tzeng Y-S, Pang C-Y, Yen P-S, et al. Functional recovery of stroke rats induced by granulocyte colony-stimulating factor–stimulated stem cells. Circulation. 2004;110:1847–54.

    Article  CAS  PubMed  Google Scholar 

  36. Du Z, Cai H, Ye Z, Tan WS. Optimization of SCF feeding regimen for ex vivo expansion of cord blood hematopoietic stem cells. J Biotechnol. 2012;164:211–9.

    Article  CAS  PubMed  Google Scholar 

  37. Koh SH, Choi HS, Park ES, Kang HJ, Ahn HS, Shin HY. Co-culture of human CD34+ cells with mesenchymal stem cells increases the survival of CD34+ cells against the 5-aza-deoxycytidine-or trichostatin A-induced cell death. Biochem Biophys Res Commun. 2005;329:1039–45.

    Article  CAS  PubMed  Google Scholar 

  38. Guilak F, Cohen DM, Estes BT, Gimble JM, Liedtke W, Chen CS. Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell. 2009;5:17–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Daley WP, Peters SB, Larsen M. Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci. 2008;121:255–64.

    Article  CAS  PubMed  Google Scholar 

  40. Metallo CM, Mohr JC, Detzel CJ, de Pablo JJ, Van Wie BJ, Palecek SP. Engineering the stem cell microenvironment. Biotechnol Prog. 2007;23:18–23.

    Article  CAS  PubMed  Google Scholar 

  41. Watt FM, Fujiwara H. Cell–extracellular matrix interactions in normal and diseased skin. Cold Spring Harb Perspect Biol. 2011;3:a005124.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Denhardt DT, et al. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood. 2005;106:1232–9.

    Article  CAS  PubMed  Google Scholar 

  43. Matrosova VY, Orlovskaya IA, Serobyan N, Khaldoyanidi SK. Hyaluronic acid facilitates the recovery of hematopoiesis following 5-fluorouracil administration. Stem Cells. 2004;22:544–55.

    Article  CAS  PubMed  Google Scholar 

  44. Rodgers KD, San Antonio JD, Jacenko O. Heparan sulfate proteoglycans: a GAGgle of skeletal–hematopoietic regulators. Dev Dyn. 2008;237:2622–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Legate KR, Wickström SA, Fässler R. Genetic and cell biological analysis of integrin outside-in signaling. Genes Dev. 2009;23:397–418.

    Article  CAS  PubMed  Google Scholar 

  46. Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978;4:7–25.

    CAS  PubMed  Google Scholar 

  47. Bari S, Seah KK, Poon Z, Cheung AM, Fan X, Ong SY, Li S, Koh LP, Hwang WY. Expansion and homing of umbilical cord blood hematopoietic stem and progenitor cells for clinical transplantation. Biol Blood Marrow Transplant. 2015;21:1008–19.

    Article  PubMed  Google Scholar 

  48. Giebe B, Bruns I. Self-renewal versus differentiation in hematopoietic stem and progenitor cells: a focus on asymmetric cell divisions. Curr Stem Cell Res Ther. 2008;3:9–16.

    Article  Google Scholar 

  49. Lambertsen RH, Weiss L. A model of intramedullary hematopoietic microenvironments based on stereologic study of the distribution of endocloned marrow colonies. Blood. 1984;63:287–97.

    CAS  PubMed  Google Scholar 

  50. Schaniel C, Moore KA. Genetic models to study quiescent stem cells and their niches. Ann N Y Acad Sci. 2009;1176:26–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Xie Y, Yin T, Wiegraebe W, He XC, Miller D, Stark D, et al. Detection of functional haematopoietic stem cell niche using real-time imaging. Nature. 2009;457:97–101.

    Article  CAS  PubMed  Google Scholar 

  52. Calvi L, Adams G, Weibrecht K, Weber J, Olson D, Knight M, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–6.

    Article  CAS  PubMed  Google Scholar 

  53. Zhang J, Niu C, Ye L, Huang H, He X, Tong W-G, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836–41.

    Article  CAS  PubMed  Google Scholar 

  54. Kiel MJ, Yilmaz ÖH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109–21.

    Article  CAS  PubMed  Google Scholar 

  55. Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell. 2007;131:324–36.

    Article  CAS  PubMed  Google Scholar 

  56. Yao C-L, Chu I-M, Hsieh T-B, Hwang S-M. A systematic strategy to optimize ex vivo expansion medium for human hematopoietic stem cells derived from umbilical cord blood mononuclear cells. Exp Hematol. 2004;32:720–7.

    Article  CAS  PubMed  Google Scholar 

  57. Kedong S, Xiubo F, Tianqing L, Macedo HM, LiLi J, Meiyun F, et al. Simultaneous expansion and harvest of hematopoietic stem cells and mesenchymal stem cells derived from umbilical cord blood. J Mater Sci Mater Med. 2010;21:3183–93.

    Article  PubMed  Google Scholar 

  58. Song K, Zhao G, Liu T, Zhang L, Ma X, Liu J, et al. Effective expansion of umbilical cord blood hematopoietic stem/progenitor cells by regulation of microencapsulated osteoblasts under hypoxic condition. Biotechnol Lett. 2009;31:923–8.

    Article  CAS  PubMed  Google Scholar 

  59. Feng Q, Chai C, Jiang XS, Leong KW, Mao HQ. Expansion of engrafting human hematopoietic stem/progenitor cells in three-dimensional scaffolds with surface-immobilized fibronectin. J Biomed Mater Res Part A. 2006;78:781–91.

    Article  Google Scholar 

  60. Ma K, Chan CK, Liao S, Hwang WY, Feng Q, Ramakrishna S. Electrospun nanofiber scaffolds for rapid and rich capture of bone marrow-derived hematopoietic stem cells. Biomaterials. 2008;29:2096–103.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The present work was supported by Fok Ying Tung Education Foundation (132027), National Science Foundation of China (31370991/31170945), the Joint Open Foundation of Natural Science Foundation of Liaoning and Shenyang National Laboratory for Materials Science (2015–2017) and the Fundamental Research Funds for the Central Universities (DUT14YQ106/15GY47), SRF for ROCS, SEM.

Author information

Authors and Affiliations

  1. State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, 116024, China

    Kedong Song, Liying Li & Tianqing Liu

  2. Burns Research Group, ANZAC Research Institute, University of Sydney, Concord, NSW, 2139, Australia

    Yiwei Wang

Authors
  1. Kedong Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yiwei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tianqing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kedong Song.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, K., Li, L., Wang, Y. et al. Hematopoietic stem cells: multiparameter regulation. Human Cell 29, 53–57 (2016). https://doi.org/10.1007/s13577-016-0134-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-016-0134-x

Keywords

Search

Navigation