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.

  • Review Article
  • Published:

Beyond chimerism analysis: methods for tracking a new generation of cell-based medicines

Bone Marrow Transplantation volume 55, pages 1229–1239 (2020)Cite this article

Subjects

Abstract

The analysis of chimerism is crucial to determine the status of patients receiving hematopoietic stem cell transplantation. The variety of relevant techniques available today range from those that analyse nucleic acids (i.e. polymerase chain reaction based, next generation sequencing) and cellular phenotype (i.e. flow cytometry) to sophisticated imaging (particularly multimodal imaging using labelling agents). However, current developments of advanced therapies bring chimerism studies into a new dimension in which methods for detection of donor cells in the patient need to adapt to a wider range of cell- and gene-based medicines, routes of administration, target organs and pathologies. Herein we describe and analyze the toolkit of suitable labelling and detection methodologies with actual examples along with a discussion on challenges ahead and potential solutions. Remarkably, existing methods commonly used in chimerism analysis are suitable for use with new cell- and gene-based medicines. Indeed, new developments may facilitate the evolution and combination of such methodologies to the use of non-invasive and highly informative approaches.

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

Fig. 1: Methodologies for tracking cell-based medicines.

Similar content being viewed by others

References

  1. Clemente I, Goncalo A, Faria C, Dias M, Barbosa I, Mendes C. Relevance of chimerism analysis after allogeneic stem cell transplantation. Transplant Proc. 2017;49:890–2.

    CAS  PubMed  Google Scholar 

  2. Khan F, Agarwal A, Agrawal S. Significance of chimerism in hematopoietic stem cell transplantation: new variations on an old theme. Bone Marrow Transplant. 2004;34:1–12.

    CAS  PubMed  Google Scholar 

  3. Boráň T, Menezes-Ferreira M, Reischl I, Celis P, Ferry N, Gänsbacher B, et al. Clinical development and commercialization of advanced therapy medicinal products in the European Union: how are the product pipeline and regulatory framework evolving? Hum Gene Ther Clin Dev. 2017;28:126–35.

    PubMed  Google Scholar 

  4. Salmikangas P, Schuessler-Lenz M, Ruiz S, Celis P, Reischl I, Menezes-Ferreira M, et al. Marketing regulatory oversight of advanced therapy medicinal products (ATMPs) in Europe: the EMA/CAT perspective. Adv Exp Med Biol. 2015;871:103–30.

    PubMed  Google Scholar 

  5. Fischbach MA, Bluestone JA, Lim WA. Cell-based therapeutics: the next pillar of medicine. Sci Transl Med. 2013;5:179ps7.

    PubMed  PubMed Central  Google Scholar 

  6. Cuende N, Rasko JEJ, Koh MBC, Dominici M, Ikonomou L. Cell, tissue and gene products with marketing authorization in 2018 worldwide. Cytotherapy. 2018;20:1401–13.

    PubMed  Google Scholar 

  7. Naji A, Eitoku M, Favier B, Deschaseaux F, Rouas-Freiss N, Suganuma N. Biological functions of mesenchymal stem cells and clinical implications. Cell Mol Life Sci. 2019;76:3323–48.

    CAS  PubMed  Google Scholar 

  8. June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379:64–73.

    CAS  Google Scholar 

  9. Vives J, Mirabel C. Multipotent mesenchymal stromal cells from bone marrow for current and potential clinical applications. In: Reis RL, editor. Encyclopedia of tissue engineering and regenerative medicine. Oxford: Academic Press; 2019. p. 503–12.

  10. Vives J, Carmona G, Vives J, Carmona G. Guide to cell therapy GxP. 1st ed. London: Academic Press (Elsevier); 2015.

  11. Sharma R. Stem cells and tissue engineering in medical practice. Curr Drug Targets. 2018;388–98.

  12. CAT, Schneider CK, Salmikangas P, Jilma B, Flamion B, Todorova LR, et al. Challenges with advanced therapy medicinal products and how to meet them. Nat Rev Drug Discov. 2010;9:195–201.

    Google Scholar 

  13. Li SC, Tachiki LM, Luo J, Dethlefs BA, Chen Z, Loudon WG. A biological global positioning system: considerations for tracking stem cell behaviors in the whole body. Stem Cell Rev. 2010;6:317–33.

    PubMed Central  Google Scholar 

  14. Reyes B, Coca MI, Codinach M, Lopez-Lucas MD, Del Mazo-Barbara A, Caminal M, et al. Assessment of biodistribution using mesenchymal stromal cells: Algorithm for study design and challenges in detection methodologies. Cytotherapy. 2017;19:1060–9.

    PubMed  Google Scholar 

  15. van Dijk BA, Drenthe-Schonk AM, Bloo A, Kunst VA, Janssen JT, de Witte TJ. Erythrocyte repopulation after allogeneic bone marrow transplantation. Analysis using erythrocyte antigens. Transplantation. 1987;44:650–4.

    PubMed  Google Scholar 

  16. Hendriks EC, de Man AJ, van Berkel YC, Stienstra S, de Witte T. Flow cytometric method for the routine follow-up of red cell populations after bone marrow transplantation. Br J Haematol. 1997;97:141–5.

    CAS  PubMed  Google Scholar 

  17. Schaap N, Schattenberg A, Bar B, Mensink E, de Man A, Geurts van Kessel A, et al. Red blood cell phenotyping is a sensitive technique for monitoring chronic myeloid leukaemia patients after T-cell-depleted bone marrow transplantation and after donor leucocyte infusion. Br J Haematol. 2000;108:116–25.

    CAS  PubMed  Google Scholar 

  18. Piagnerelli M, Zouaoui Boudjeltia K, Brohee D, Vereerstraeten A, Piro P, Vincent JL, et al. Assessment of erythrocyte shape by flow cytometry techniques. J Clin Pathol. 2007;60:549–54.

    CAS  PubMed  Google Scholar 

  19. Diez B, Genovese P, Roman-Rodriguez FJ, Alvarez L, Schiroli G, Ugalde L, et al. Therapeutic gene editing in CD34(+) hematopoietic progenitors from Fanconi anemia patients. EMBO Mol Med. 2017;9:1574–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Butturini A, Gale RP, Verlander PC, Adler-Brecher B, Gillio AP, Auerbach AD. Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study. Blood. 1994;84:1650–5.

    CAS  PubMed  Google Scholar 

  21. Río P, Navarro S, Wang W, Sánchez-Domínguez R, Pujol RM, Segovia JC, et al. Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia. Nat Med. 2019;25:1396–401.

    PubMed  Google Scholar 

  22. Wilkins O, Keeler AM, Flotte TR. CAR T-cell therapy: progress and prospects. Hum Gene Ther Methods. 2017;28:61–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Zheng Z, Chinnasamy N, Morgan RA. Protein L: a novel reagent for the detection of chimeric antigen receptor (CAR) expression by flow cytometry. J Transl Med. 2012;10:29.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhang C, Wang Z, Yang Z, Wang M, Li S, Li Y, et al. Phase I escalating-dose trial of CAR-T therapy targeting CEA. Mol Ther. 2017;25:1248–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Jólkowska J, Pieczonka A, Strabel T, Boruczkowski D, Wachowiak J, Bader P, et al. Hematopoietic chimerism after allogeneic stem cell transplantation: a comparison of quantitative analysis by automated DNA sizing and fluorescent in situ hybridization. BMC Blood Disord. 2005;5:1.

    PubMed  PubMed Central  Google Scholar 

  26. Erlecke J, Hartmann I, Hoffmann M, Kroll T, Starke H, Heller A, et al. Automated detection of residual cells after sex-mismatched stem-cell transplantation - evidence for presence of disease-marker negative residual cells. Mol Cytogenet. 2009;2:12.

    PubMed  PubMed Central  Google Scholar 

  27. Dewald GW, Schad CR, Christensen ER, Law ME, Zinsmeister AR, Stalboerger PG, et al. Fluorescence in situ hybridization with X and Y chromosome probes for cytogenetic studies on bone marrow cells after opposite sex transplantation. Bone Marrow Transplant. 1993;12:149–54.

    CAS  PubMed  Google Scholar 

  28. Hibi S, Tsunamoto K, Todo S, Sawada T, Ueda Y, Taniwaki M, et al. Chimerism analysis on mononuclear cells in the CSF after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1997;20:503–6.

    CAS  PubMed  Google Scholar 

  29. Buño I, Nava P, Simón A, González-Rivera M, Jiménez JL, Balsalobre P, et al. A comparison of fluorescent in situ hybridization and multiplex short tandem repeat polymerase chain reaction for quantifying chimerism after stem cell transplantation. Haematologica. 2005;90:1373–9.

    PubMed  Google Scholar 

  30. Chaterji S, Ahn EH, Kim DH. CRISPR genome engineering for human pluripotent stem cell research. Theranostics. 2017;7:4445–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Chen B, Gilbert LA, Cimini BA, Schnitzbauer J, Zhang W, Li GW, et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell. 2013;155:1479–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Deng W, Shi X, Tjian R, Lionnet T, Singer RH. CASFISH: CRISPR/Cas9-mediated in situ labeling of genomic loci in fixed cells. Proc Natl Acad Sci USA. 2015;112:11870–5.

    CAS  PubMed  Google Scholar 

  33. Poloni A, Leoni P, Buscemi L, Balducci F, Pasquini R, Masia MC, et al. Engraftment capacity of mesenchymal cells following hematopoietic stem cell transplantation in patients receiving reduced-intensity conditioning regimen. Leukemia. 2006;20:329–35.

    CAS  PubMed  Google Scholar 

  34. Fujisawa M, Hayashi K, Nishio T, Bando T, Okada S, Yamato KT, et al. Isolation of X and Y chromosome-specific DNA markers from a liverwort, Marchantia polymorpha, by representational difference analysis. Genetics. 2001;159:981–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Yamane A, Karasawa M, Maehara T, Tsukamoto N, Nojima Y. X chromosome methylation-based chimerism assay for sex-mismatched hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;28:969–73.

    CAS  PubMed  Google Scholar 

  36. Aloisio M, Licastro D, Caenazzo L, Torboli V, D’Eustacchio A, Severini GM, et al. A technical application of quantitative next generation sequencing for chimerism evaluation. Mol Med Rep. 2016;14:2967–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Kletzel M, Huang W, Olszewski M, Khan S. Validation of chimerism in pediatric recipients of allogeneic hematopoietic stem cell transplantation (HSCT) a comparison between two methods: real-time PCR (qPCR) vs. variable number tandem repeats PCR (VNTR PCR). Chimerism. 2013;4:1–8.

    PubMed  Google Scholar 

  38. Alizadeh M, Bernard M, Danic B, Dauriac C, Birebent B, Lapart C, et al. Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction. Blood. 2002;99:4618–25.

    CAS  PubMed  Google Scholar 

  39. Kuang J, Yan X, Genders AJ, Granata C, Bishop DJ. An overview of technical considerations when using quantitative real-time PCR analysis of gene expression in human exercise research. PLoS ONE. 2018;13:e0196438.

    PubMed  PubMed Central  Google Scholar 

  40. Kim SY, Jeong MH, Park N, Ra E, Park H, Seo SH, et al. Chimerism monitoring after allogeneic hematopoietic stem cell transplantation using quantitative real-time PCR of biallelic insertion/deletion polymorphisms. J Mol Diagn. 2014;16:679–88.

    CAS  PubMed  Google Scholar 

  41. Jimenez-Velasco A, Barrios M, Roman-Gomez J, Navarro G, Buno I, Castillejo JA, et al. Reliable quantification of hematopoietic chimerism after allogeneic transplantation for acute leukemia using amplification by real-time PCR of null alleles and insertion/deletion polymorphisms. Leukemia. 2005;19:336–43.

    CAS  PubMed  Google Scholar 

  42. Thiede C, Bornhauser M, Ehninger G. Strategies and clinical implications of chimerism diagnostics after allogeneic hematopoietic stem cell transplantation. Acta Haematol. 2004;112:16–23.

    PubMed  Google Scholar 

  43. Huggett JF, Cowen S, Foy CA. Considerations for digital PCR as an accurate molecular diagnostic tool. Clin Chem. 2015;61:79–88.

    CAS  PubMed  Google Scholar 

  44. Kliman D, Castellano-Gonzalez G, Withers B, Street J, Tegg E, Mirochnik O, et al. Ultra-sensitive droplet digital PCR for the assessment of microchimerism in cellular therapies. Biol Blood Marrow Transplant. 2018;24:1069–78.

    CAS  PubMed  Google Scholar 

  45. Mika T, Baraniskin A, Ladigan S, Wulf G, Dierks S, Haase D, et al. Digital droplet PCR-based chimerism analysis for monitoring of hematopoietic engraftment after allogeneic stem cell transplantation. Int J Lab Hematol. 2019;41:615–21.

    PubMed  Google Scholar 

  46. Valero-Garcia J, González-Espinosa MDC, Barrios M, Carmona-Antoñanzas G, García-Planells J, Ruiz-Lafora C, et al. Earlier relapse detection after allogeneic haematopoietic stem cell transplantation by chimerism assays: digital PCR versus quantitative real-time PCR of insertion/deletion polymorphisms. PLoS ONE. 2019;14:e0212708.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Lin HT, Okumura T, Yatsuda Y, Ito S, Nakauchi H, Otsu M. Application of droplet digital PCR for estimating vector copy number states in stem cell gene therapy. Hum Gene Ther Methods. 2016;27:197–208.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Jin W, Liang X, Brooks A, Futrega K, Liu X, Doran MR, et al. Modelling of the SDF-1/CXCR4 regulated. PeerJ. 2018;6:e6072.

    PubMed  PubMed Central  Google Scholar 

  49. Gu E, Chen WY, Gu J, Burridge P, Wu JC. Molecular imaging of stem cells: tracking survival, biodistribution, tumorigenicity, and immunogenicity. Theranostics. 2012;2:335–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Mukherjee A, Tipnis S, Sarma HD, Ravindran G, Samuel G, Viswanathan C, et al. Radiolabeling of umbilical cord-derived mesenchymal stem cells for in vivo tracking. Cancer Biother Radiopharm. 2012;27:614–9.

    CAS  PubMed  Google Scholar 

  51. Giarratana MC, Rouard H, Dumont A, Kiger L, Safeukui I, Le Pennec PY, et al. Proof of principle for transfusion of in vitro-generated red blood cells. Blood. 2011;118:5071–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Cheng SH, Yu D, Tsai HM, Morshed RA, Kanojia D, Lo LW, et al. Dynamic in vivo SPECT imaging of neural stem cells functionalized with radiolabeled nanoparticles for tracking of glioblastoma. J Nucl Med. 2016;57:279–84.

    CAS  PubMed  Google Scholar 

  53. Kurpisz M, Czepczyński R, Grygielska B, Majewski M, Fiszer D, Jerzykowska O, et al. Bone marrow stem cell imaging after intracoronary administration. Int J Cardiol. 2007;121:194–5.

    CAS  PubMed  Google Scholar 

  54. Serganova I, Ponomarev V, Blasberg R. Human reporter genes: potential use in clinical studies. Nucl Med Biol. 2007;34:791–807.

    CAS  PubMed  Google Scholar 

  55. Gholamrezanezhad A, Mirpour S, Bagheri M, Mohamadnejad M, Alimoghaddam K, Abdolahzadeh L, et al. In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis. Nucl Med Biol. 2011;38:961–7.

    CAS  PubMed  Google Scholar 

  56. Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lonnies H, et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation. 2006;81:1390–7.

    PubMed  Google Scholar 

  57. Vo D, Nguyen PK. Multimodality molecular imaging in cardiac regenerative therapy. J Nucl Cardiol. 2017;24:1803–9.

    PubMed  Google Scholar 

  58. Brooks A, Futrega K, Liang X, Hu X, Liu X, Crawford DHG, et al. Concise review: quantitative detection and modeling the in vivo kinetics of therapeutic mesenchymal stem/stromal cells. Stem Cells Transl Med. 2018;7:78–86.

    PubMed  Google Scholar 

  59. Ahrens ET, Bulte JW. Tracking immune cells in vivo using magnetic resonance imaging. Nat Rev Immunol. 2013;13:755–63.

    CAS  PubMed  Google Scholar 

  60. Wu B, Warnock G, Zaiss M, Lin C, Chen M, Zhou Z, et al. An overview of CEST MRI for non-MR physicists. EJNMMI Phys. 2016;3:19.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Janowski M, Walczak P, Kropiwnicki T, Jurkiewicz E, Domanska-Janik K, Bulte JW, et al. Long-term MRI cell tracking after intraventricular delivery in a patient with global cerebral ischemia and prospects for magnetic navigation of stem cells within the CSF. PLoS ONE. 2014;9:e97631.

    PubMed  PubMed Central  Google Scholar 

  62. Gayathri K, Shailendhra K. MRI and blood flow in human arteries: are there any adverse effects? Cardiovasc Eng Technol. 2019;10:242–56.

    CAS  PubMed  Google Scholar 

  63. Kim SJ, Lewis B, Steiner MS, Bissa UV, Dose C, Frank JA. Superparamagnetic iron oxide nanoparticles for direct labeling of stem cells and in vivo MRI tracking. Contrast Media Mol Imaging. 2016;11:55–64.

    CAS  PubMed  Google Scholar 

  64. Kirsch M, Wannez S, Thibaut A, Laureys S, Brichant JF, Bonhomme V. Positron emission tomography: basic principles, new applications, and studies under anesthesia. Int Anesthesiol Clin. 2016;54:109–28.

    PubMed  Google Scholar 

  65. Hsu MJ, Prigent J, Dollet PE, Ravau J, Larbanoix L, Van Simaeys G, et al. Long-term in vivo monitoring of adult-derived human liver stem/progenitor cells by bioluminescence imaging, positron emission tomography, and contrast-enhanced computed tomography. Stem Cells Dev. 2017;26:986–1002.

    CAS  PubMed  Google Scholar 

  66. Williams KM, Holter-Chakrabarty J, Lindenberg L, Duong Q, Vesely SK, Nguyen CT, et al. Imaging of subclinical haemopoiesis after stem-cell transplantation in patients with haematological malignancies: a prospective pilot study. Lancet Haematol. 2018;5:e44–52.

    PubMed  Google Scholar 

  67. Hancock JP, Burgess MF, Goulden NJ, Steward CG, Knechtli CJ, Pamphilon DH, et al. Same-day determination of chimaeric status in the immediate period following allogeneic bone marrow transplantation. Br J Haematol. 1997;99:403–9.

    CAS  PubMed  Google Scholar 

  68. Nakao S, Nakatsumi T, Chuhjo T, Ohtaguro M, Tsuchiya H, Niki T, et al. Analysis of late graft failure after allogeneic bone marrow transplantation: detection of residual host cells using amplification of variable number of tandem repeats loci. Bone Marrow Transplant. 1992;9:107–11.

    CAS  PubMed  Google Scholar 

  69. Zeineldin R. 7—Nanotechnology for cancer screening and diagnosis. In: Park K, editor. Biomaterials for Cancer Therapeutics: Woodhead Publishing; 2013. p. 137–64.

  70. Hicks R, Lau E, Binns D. Hybrid imaging is the future of molecular imaging. Biomed Imaging Interv J. 2007;3:e49.

    PubMed  PubMed Central  Google Scholar 

  71. Ruf J, Lopez Hänninen E, Böhmig M, Koch I, Denecke T, Plotkin M, et al. Impact of FDG-PET/MRI image fusion on the detection of pancreatic cancer. Pancreatology. 2006;6:512–9.

    CAS  PubMed  Google Scholar 

  72. Catana C, Wu Y, Judenhofer MS, Qi J, Pichler BJ, Cherry SR. Simultaneous acquisition of multislice PET and MR images: initial results with a MR-compatible PET scanner. J Nucl Med. 2006;47:1968–76.

    PubMed  Google Scholar 

  73. Sensebé L, Fleury-Cappellesso S. Biodistribution of mesenchymal stem/stromal cells in a preclinical setting. Stem Cells Int. 2013;2013:678063.

    PubMed  PubMed Central  Google Scholar 

  74. Huang T, Deng CX. Current progresses of exosomes as cancer diagnostic and prognostic biomarkers. Int J Biol Sci. 2019;15:1–11.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are grateful to Dr Belén Ansoleaga for critically reviewing the paper. This work has been developed in the context of ADVANCE(CAT) with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) and the European Community under the Catalonian ERDF operational programme (European Regional Development Fund) 2014–2020, Generalitat de Catalunya (Departament de Salut) PERIS Acció Instrumental de Programes de Recerca Orientats (SLT002/16/00234) and by the Spanish Cell Therapy Network (TerCel, expedient number: RD16/0011/0028). Project PI19/01788 is funded by Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF)—a way to build Europe. JV’s laboratory is awarded by the Generalitat de Catalunya as Consolidated Research Group (ref. 2017SGR719). NN has been supported by Fundació La Marató de TV3 (File number 20133230).

Author information

Authors and Affiliations

  1. Servei de Teràpia Cel·lular, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005, Barcelona, Spain

    Joaquim Vives, Aina Casademont-Roca & Lluís Martorell

  2. Musculoskeletal Tissue Engineering Group, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig de la Vall d’Hebron 129-139, 08035, Barcelona, Spain

    Joaquim Vives & Lluís Martorell

  3. Departament de Medicina, Universitat Autònoma de Barcelona, Passeig de la Vall d’Hebron 129-139, 08035, Barcelona, Spain

    Joaquim Vives & Núria Nogués

  4. Laboratori d’Immunohematologia, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005, Barcelona, Spain

    Núria Nogués

Authors
  1. Joaquim Vives
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aina Casademont-Roca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lluís Martorell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Núria Nogués
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JV and NN conceived the study; JV, AC-R, LM and NN collected information, wrote the paper and approved the final version.

Corresponding author

Correspondence to Joaquim Vives.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vives, J., Casademont-Roca, A., Martorell, L. et al. Beyond chimerism analysis: methods for tracking a new generation of cell-based medicines. Bone Marrow Transplant 55, 1229–1239 (2020). https://doi.org/10.1038/s41409-020-0822-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-0822-8

This article is cited by

Search

Advanced search

Quick links