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.

  • Technical Report
  • Published:

Essential requirements for setting up a stem cell processing laboratory

Bone Marrow Transplantation volume 49, pages 1098–1105 (2014)Cite this article

Subjects

Abstract

The Graft Processing subcommittee of the Worldwide Network for Blood and Marrow Transplantation wrote this guideline to assist physicians and laboratory technologists with the setting up of a cell processing laboratory (CPL) to support a hematopoietic stem cell transplant program, thereby facilitating the start-up of a transplant program in a new location and improving patient access to transplantation worldwide. This guideline describes the minimal essential features of designing such a laboratory and provides a list of equipment and supply needs and staffing recommendations. It describes the typical scope of services that a CPL is expected to perform, including product testing services, and discusses the basic principles behind the most frequent procedures. Quality management (QM) principles specific to a CPL are also discussed. References to additional guidance documents that are available worldwide to assist with QM and regulatory compliance are also provided.

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

Similar content being viewed by others

References

  1. Worldwide Network for Blood and Marrow Transplantation (WBMT). www.wbmt.org.

  2. 21 Code of Federal Regulations Part 1271. www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=1271.

  3. Regulation(EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004.

  4. Burger SR . Design and operation of a current good manufacturing practices cell engineering laboratory. Cytotherapy 2000; 2: 11–122.

    Article  Google Scholar 

  5. Schwartz J, Padmanabhan A, Francis R, Lindenberger M . Mobilization and collection of peripheral blood hematopoietic progenitor cells. In: McLeod B, Szczepiorkowski M, Weinstein R, Winters J (eds). Apheresis Principles and Practice, 3rd edn. AABB Press: Bethesda, MD, 2010.

  6. Matsumoto N, Yoshizawa H, Kagamu H, Abe T, Fujita N, Watanabe S et al. Successful liquid storage of peripheral blood stem cells at subzero non-freezing temperature. Bone Marrow Transplant 2002; 30: 777–784.

    Article  CAS  Google Scholar 

  7. Antonenas V, Garvin F, Webb M, Sartor M, Bradstock KF, Gottlieb D et al. PBSC harvests, but not BM, show temperature-related loss of CD34 viability during storage and transport. Cytotherapy 2006; 8: 158–165.

    Article  CAS  Google Scholar 

  8. McCullough J, Haley R, Clay M, Hubel A, Lindgren B, Moroff G . Long-term storage of peripheral blood stem cells frozen and stored with a conventional liquid nitrogen technique compared with cells frozen and stored in a mechanical freezer. Transfusion 2010; 50: 808–819.

    Article  Google Scholar 

  9. Costa R, Khattab M, Gilmore GL, Sahovic EA, Miller SM, Rossetti JM et al. Viability and potency of hematopoietic progenitor cells after prolonged cryopreservation at –80 ° C. Acta Haematol 2011; 126: 99–102.

    Article  Google Scholar 

  10. Makino S, Harada M, Akashi K, Taniguchi S, Shibuya T, Inaba S et al. A simplified method for cryopreservation of peripheral blood stem cells at −80 degrees C without rate-controlled freezing. Bone Marrow Transplant 1991; 8: 239–244.

    CAS  PubMed  Google Scholar 

  11. Watts MJ, Sullivan AM, Ings SJ, Barlow M, Devereux S, Goldstone AH et al. Storage of PBSC at -80oC. Bone Marrow Transplant 1998; 21: 111–112.

    Article  CAS  Google Scholar 

  12. Rowley SD . Hematopoietic stem cell cryopreservation: a review of current techniques. J Hematother 1992; 1: 233–250.

    Article  CAS  Google Scholar 

  13. Rowley SD, Feng Z, Chen L, Holmberg L, Heimfeld S, MacLeod B et al. A randomized phase III clinical trial of autologous blood stem cell transplantation comparing cryopreservation using dimethylsulfoxide versus dimethylsulfoxide with hydroxyethylstarch. Bone Marrow Transplant 2003; 31: 1043–1051.

    Article  CAS  Google Scholar 

  14. Cabezudo E, Dalmases C, Ruz M, Sanchez JA, Torrico C, Sola C et al. Leukapheresis components may be cryopreserved at high cell concentrations without additional loss of HPC function. Transfusion 2000; 40: 1223–1227.

    Article  CAS  Google Scholar 

  15. Sanchez-Salinas A, Cabanas-Perianes V, Blanquer M, Majado MJ, Insausti CL, Monserrat J et al. An automatic wash method for dimethylsulfoxide removal in autologous hematopoietic stem cell transplantation decreases the adverse effects related to infusion. Transfusion 2012; 52: 2382–2386.

    Article  Google Scholar 

  16. Areman E, Deeg HJ, Sacher RA (eds). Bone Marrow and Stem Cell Processing: A Manual of Current Techniques. FA Davis Co: Philadelphia, PA, USA, 1992.

  17. Leemhuis T, Sacher R . Hematopoietic progenitor cells: biology and processing. In: Simon T, Snyder E, Solheim B, Stowell C, Strauss R, Petrides M (eds). Rossi’s Principles of Transfusion Medicine, 4th edn. Wiley Blackwell: West Sussex, UK, 2009.

    Google Scholar 

  18. Davis-Sproul J, Haley NR, McMannis J . Collecting and processing marrow products for transplantation. In: Roback JD, Grossman BJ, Harris T, Hilyer CD (eds). Technical Manual. AABB Press: Bethesda, MD, 2011.

  19. International Society for Cellular Therapy [homepage on the Internet]: Vancouver, BC, USA. [updated 2011] Available from: http://www.celltherapysociety.org.

  20. American Association of Blood Banks [homepage on the Internet]: Bethesda, MD, USA. [updated 2013] Available from: http://www.AABB.org.

  21. Rowley SD, Anderson GL . Effect of DMSO exposure without cryopreservation on hematopoietic progenitor cells. Bone Marrow Transplant 1993; 11: 389–393.

    CAS  PubMed  Google Scholar 

  22. Rubinstein P, Dobrila L, Rosenfield RE, Adamson JW, Migliaccio G, Migliaccio AR et al. Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. Proc Natl Acad Sci USA 1995; 92: 10119–10122.

    Article  CAS  Google Scholar 

  23. Windrum P, Morris TC, Drake MB, Niederwieser D, Ruutu T, on behalf of the EBMT Chronic Leukaemia Working Party Complications Subcommittee. Variation in dimethyl sulfoxide use in stem cell transplantation: a survey of EBMT centres. Bone Marrow Transplant 2005; 36: 601–603.

    Article  CAS  Google Scholar 

  24. AABB, America’s Blood Centers, American Association of Tissue Banks, American Red Cross, American Society for Apheresis, American Society for Blood and Marrow Transplantation, College of American Pathologists, Foundation for the Accreditation of Cellular Therapy, ICCBBA, International Society for Cellular Therapy, Joint Accreditation Committee, National Marrow Donor Program, and Netcord Circular of information for the use of cellular therapy products. AABB: Bethesda, MD, USA, 2009.

  25. Wuest DL, Reich LM . Removal of ABO-incompatible red cells from lymphocytapheresis and granulocytapheresis components before transfusion. Transfusion 1997; 37: 144–149.

    Article  CAS  Google Scholar 

  26. Larghero J, Rea D, Esperou H, Biscay N, Maure M-N, Lacassagne M-N et al. ABO-mismatched marrow processing for transplantation: results of 114 procedures and analysis of immediate adverse events and hematopoietic recovery. Transfusion 2006; 46: 398–402.

    Article  CAS  Google Scholar 

  27. Rowley SD . Hematopoietic stem cell transplantation between red cell incompatible donor-recipient pairs. Bone Marrow Transplant 2001; 28: 315–321.

    Article  CAS  Google Scholar 

  28. International Council for Commonality in Blood Banking Automation, Inc. [homepage on the Internet]: San Bernadino, CA, USA. [updated 2012] Available from http://www.iccbba.org.

  29. Kozuka T, Ikeda K, Teshima T, Kojima K, Matsuo K, Bessho A et al. Predictive value of circulating immature cell counts in peripheral blood for timing of peripheral blood progenitor cell collection after G-CSF plus chemotherapy-induced mobilization. Transfusion 2002; 42: 1514–1522.

    Article  Google Scholar 

  30. Teshima T, Sunami K, Bessho A, Shinagawa K, Omoto E, Ueoka H et al. Circulating immature cell counts on the harvest day predict the yields of CD34+ cells collected after G-CSF plus chemotherapy-induced mobilization of peripheral blood stem cells. Blood 1997; 89: 4660–4661.

    CAS  PubMed  Google Scholar 

  31. Bandarenko M, Sims LC, Brecher ME . Circulating CD34+ cell counts are predictive of CD34+ peripheral blood progenitor cell yields, (letter). Transfusion 1997; 37: 1218–1220.

    Article  CAS  Google Scholar 

  32. 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 

  33. Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR . Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry 1998; 34: 61–70.

    Article  CAS  Google Scholar 

  34. Keeney M, Brown W, Gratama J, Papa S, Lanza F, Sutherland R . European Working Group on Clinical Cell Analysis. Single platform enumeration of viable CD34+ cells. J Biol Regul Homeost Agents 2003; 17: 247–253.

    CAS  PubMed  Google Scholar 

  35. Keeney M, Brown W, Gratama J, Papa S, Lanza F, Sutherland R . Compensation and autostandardizaton protocol for CD34 analysis. J Biol Regul 2003; 17: 261–266.

    CAS  Google Scholar 

  36. Standards for Cellular Therapy Product Services, 5th edn. American Association of Blood Banks: Bethesda, MD, USA, 2011.

  37. FACT-JACIE International Standards for Cellular Therapy Product Collection, Processing and Administration. Foundation for the Accreditation of Cellular Therapy, and the Joint Accreditation Committee, 5th edn. ISCT, EBMT: Omaha, NE, USA, 2012.

  38. Center for International Blood and Marrow Transplant Research [homepage on the Internet]. Milwaukee, WI, USA. [updated 2011] Available from: http://www.cibmtr.org.

  39. Foundation for the Accreditation of Cellular Therapy [homepage on the Internet]: Omaha, NE, USA. [updated 2012] Available from: http://www.FACTwebsite.org.

  40. Joint Accreditation Committee ISCT (Europe)-EBMT [homepage on the Internet]. Barcelona, Spain. [updated 2013] Available from: http://www.jacie.org.

  41. International Netcord Foundation [homepage on the Internet]. Arlington Heights, IL, USA. [updated 2013] Available from: http://www.netcord.org.

Download references

Author information

Authors and Affiliations

  1. Hoxworth Blood Center, University of Cincinnati Academic Health Center, Cincinnati, OH, USA

    T Leemhuis

  2. Human Cellular Therapy Laboratory Mayo Clinic, Rochester, MN, USA

    D Padley

  3. Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    C Keever-Taylor

  4. Division of Hematology and Medical Oncology, University of Leipzig, Johannisallee 32A, Leipzig, Germany

    D Niederwieser

  5. Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    T Teshima

  6. Section of Hematology & BMT unit, Hospital of Cremona, Cremona, Italy

    F Lanza

  7. Institut Paoli-Calmettes & Inserm CBT-510, Marseilles, France

    C Chabannon

  8. Division of Blood and Marrow Transplantation and Cellular Therapies Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, Pittsburgh, PA, USA

    P Szabolcs

  9. Department of internal Medicine and BMT program, American University of Beirut Medical Center, Beirut, Lebanon

    A Bazarbachi

  10. Stem Cell Transplant Programme, St George’s Hospital and Medical School, London, UK

    M B C Koh

  11. Blood Services Group, Health Sciences Authority, Outram Road, Singapore

    M B C Koh

Authors
  1. T Leemhuis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Padley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Keever-Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D Niederwieser
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Teshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F Lanza
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Chabannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P Szabolcs
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Bazarbachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M B C Koh
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the Graft Processing Subcommittee of the Worldwide Network for Blood and Bone Marrow Transplantation (WBMT)

Corresponding author

Correspondence to M B C Koh.

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

Leemhuis, T., Padley, D., Keever-Taylor, C. et al. Essential requirements for setting up a stem cell processing laboratory. Bone Marrow Transplant 49, 1098–1105 (2014). https://doi.org/10.1038/bmt.2014.104

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2014.104

Search

Advanced search

Quick links