Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Lost in Transplantation? Unexpected shift from multipotent to late lymphomyeloid hematopoietic stem and progenitor cells in patients 1 year after hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 51, pages 1073–1075 (2016)Cite this article

Subjects

Transplantation of human hematopoietic stem cell (HSC) containing grafts has emerged as a standard therapy to cure several diseases, especially leukemia. In 2014, a record number of 40 829 HSC transplantations (HSCTs) were performed in Europe, out of which 42% were allogeneic.1 Conventionally, the total nucleated cell count (TNC) and the content of CD34+ cells are used as quality control criteria for HSC grafts.2, 3 Some groups consider TNC to be a better predictor of HSCT outcomes than the number of transplanted CD34+ cells.4 This might be related to the heterogeneity of the CD34+ cell fraction. Although human HSCs are included in the CD34+ cell fraction, this population contains a mixture of different hematopoietic stem and progenitor cells (HSPCs). Novel cell surface marker combinations now allow for the dissection of CD34+ populations into different HSPC types either being multipotent or committed to the lymphomyeloid or erythromyeloid lineages.5, 6, 7, 8, 9 Although the analysis of CD34+ subpopulations has massively increased our understanding in early human hematopoiesis, such subpopulation analyses have only been reported for HSCT grafts, but not for the reconstituted bone marrow (BM) following HSCT.5, 7, 10, 11, 12

Now, Dmytrus et al.13 have comprehensively analyzed HSPC subpopulations in grafts before and in the BM of patients 1 year after HSCT. Interestingly, in comparison with the original grafts, the authors observed a significant decrease in more primitive and an increase in more mature HSPC frequencies after HSCT. Here we summarize and discuss these findings in a broader context.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Passweg JR, Baldomero H, Bader P, Bonini C, Cesaro S, Dreger P et al. Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually. Bone Marrow Transplant (e-pub ahead of print 22 February 2016; doi:10.1038/bmt.2016.20).

    Article  CAS  Google Scholar 

  2. Sutherland DR, Nayyar R, Acton E, Giftakis A, Dean S, Mosiman VL . Comparison of two single-platform ISHAGE-based CD34 enumeration protocols on BD FACSCalibur and FACSCanto flow cytometers. Cytotherapy 2009; 11: 595–605.

    Article  CAS  Google Scholar 

  3. Sutherland DR, Anderson L, Keeney M, Nayar R, Chin-Yee I . The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering. J Hematother 1996; 5: 213–226.

    Article  CAS  Google Scholar 

  4. Martin PS, Li S, Nikiforow S, Alyea EP 3rd, Antin JH, Armand P et al. Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34+ cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation. Haematologica 2016; 101: 499–505.

    Article  CAS  Google Scholar 

  5. Radtke S, Gorgens A, Kordelas L, Schmidt M, Kimmig KR, Koninger A et al. CD133 allows elaborated discrimination and quantification of haematopoietic progenitor subsets in human haematopoietic stem cell transplants. Br J Haematol 2015; 169: 868–878.

    Article  CAS  Google Scholar 

  6. Gorgens A, Radtke S, Mollmann M, Cross M, Durig J, Horn PA et al. Revision of the human hematopoietic tree: granulocyte subtypes derive from distinct hematopoietic lineages. Cell Rep 2013; 3: 1539–1552.

    Article  Google Scholar 

  7. D'Arena G, Musto P, Cascavilla N, Di Giorgio G, Zendoli F, Carotenuto M . Human umbilical cord blood: immunophenotypic heterogeneity of CD34+ hematopoietic progenitor cells. Haematologica 1996; 81: 404–409.

    CAS  PubMed  Google Scholar 

  8. Doulatov S, Notta F, Eppert K, Nguyen LT, Ohashi PS, Dick JE . Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development. Nat Immunol 2010; 11: 585–593.

    Article  CAS  Google Scholar 

  9. Kohn LA, Hao QL, Sasidharan R, Parekh C, Ge S, Zhu Y et al. Lymphoid priming in human bone marrow begins before expression of CD10 with upregulation of L-selectin. Nat Immunol 2012; 13: 963–971.

    Article  CAS  Google Scholar 

  10. Gonzalez-Requejo A, Madero L, Diaz MA, Villa M, Garcia-Escribano C, Balas A et al. Progenitor cell subsets and engraftment kinetics in children undergoing autologous peripheral blood stem cell transplantation. Br J Haematol 1998; 101: 104–110.

    Article  CAS  Google Scholar 

  11. Bender JG, Unverzagt K, Walker DE, Lee W, Smith S, Williams S et al. Phenotypic analysis and characterization of CD34+ cells from normal human bone marrow, cord blood, peripheral blood, and mobilized peripheral blood from patients undergoing autologous stem cell transplantation. Clin Immunol Immunopathol 1994; 70: 10–18.

    Article  CAS  Google Scholar 

  12. Pastore D, Mestice A, Perrone T, Gaudio F, Delia M, Albano F et al. Subsets of CD34+ and early engraftment kinetics in allogeneic peripheral SCT for AML. Bone Marrow Transplant 2008; 41: 977–981.

    Article  CAS  Google Scholar 

  13. Dmytrus J, Matthes-Martin S, Pichler H, Worel N, Geyeregger R, Frank N et al. Multi-color immune-phenotyping of CD34 subsets reveals unexpected differences between various stem cell sources. Bone Marrow Transplant (e-pub ahead of print 4 April 2016; doi:10.1038/bmt.2016.88).

    Article  CAS  Google Scholar 

  14. Gorgens A, Radtke S, Horn PA, Giebel B . New relationships of human hematopoietic lineages facilitate detection of multipotent hematopoietic stem and progenitor cells. Cell Cycle 2013; 12: 3478–3482.

    Article  Google Scholar 

  15. Görgens A, Ludwig AK, Möllmann M, Krawczyk A, Dürig J, Hanenberg H et al. Multipotent hematopoietic progenitors divide asymmetrically to create progenitors of the lympho-myeloid and erythro-myeloid lineages. Stem Cell Reports 2014; 3: 1058–1072.

    Article  Google Scholar 

  16. Murke F, Castro S, Giebel B, Görgens A . Concise review: asymmetric cell divisions in stem cell biology. Symmetry 2015; 7: 2025–2037.

    Article  CAS  Google Scholar 

  17. Radtke S, Görgens A, Liu B, Horn PA, Giebel B . Human mesenchymal and murine stromal cells support human lympho-myeloid progenitor expansion but not maintenance of multipotent haematopoietic stem and progenitors cells. Cell Cycle 2016; 15: 540–545.

    Article  CAS  Google Scholar 

  18. Jaime-Pérez JC, Villarreal-Villarreal CD, Méndez-Ramírez N, Vázquez-Garza E, Salazar-Riojas R, Gómez-Almaguer D . Assessment of immune reconstitution status in recipients of a successful hematopoietic stem cell transplant from peripheral blood after reduced intensity conditioning. Blood Cells Mol Dis 2016; 58: 52–56.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    A Görgens, F Murke & B Giebel

  2. Department for Bone Marrow Transplantation, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    L Kordelas

Authors
  1. A Görgens
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F Murke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Kordelas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B Giebel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to A Görgens or B Giebel.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Görgens, A., Murke, F., Kordelas, L. et al. Lost in Transplantation? Unexpected shift from multipotent to late lymphomyeloid hematopoietic stem and progenitor cells in patients 1 year after hematopoietic stem cell transplantation. Bone Marrow Transplant 51, 1073–1075 (2016). https://doi.org/10.1038/bmt.2016.146

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2016.146

Search

Advanced search

Quick links