Summary:
We have reported short periods of post transplant neutropenia in human patients co-transplanted with cord blood (CB) and low numbers of haploidentical mobilized peripheral blood (MPB) CD34+ cells. To investigate the effect that the proportion of MPB to CB cells may have on engraftment kinetics, we have co-transplanted fixed numbers of human CB CD34+ cells mixed with different numbers of MPB CD34+ cells into NOD/SCID mice. We periodically quantified the proportion of human cells and the relative contribution of MPB and CB cells to the human engraftment on marrow aspirates. At the lowest MPB/CB ratios (5 : 1, 10 : 1), the contribution of CB cells predominated at all time points analyzed, and in three out of four experiments MPB cell contributions progressively decreased from day +15. At higher MPB/CB ratios, MPB cells had a more important contribution to both early and late engraftment, with the highest cell ratio resulting in only marginal CB cell engraftment. Therefore, our results showed greater potential, on a per cell basis, of human CB vs MPB cells for competitive sustained engraftment in the xenogeneic model used, which was only abrogated by the co-infusion of very high numbers of MPB cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Gluckman E, Rocha V, Boyer-Chammard A et al. Outcome of cord blood transplantation from related and unrelated donors. N Engl J Med 1997; 337: 373–381.
Rubinstein P, Carrier C, Scaradavou A et al. Outcome among 562 recipients of placental blood transplants from unrelated donors. N Engl J Med 1998; 339: 1565–1577.
Gluckman E . Status of umbilical cord blood hematopoietic transplantation. Exp Hematol 2000; 28: 1197–1205.
Wagner JE, Barker JN, DeFor T et al. Transplantation of unrelated donor umbilical cord blood in 2 patients with malignant and non-malignant disease: influence of CD34+ cell dose and HLA disparity on treatment related mortality and survival. Blood 2002; 100: 1611–1618.
Rocha V, Cornish J, Sievers EL et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukaemia. Blood 2001; 97: 2962–2971.
Michel G, Rocha V, Chevret S et al. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord group analysis. Blood 2003; 102: 4290–4297.
Takahashi S, Iseki T, Ooi J et al. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematological malignancies. Blood First Edition Paper. Prepublished Online July 27, 2004; DOI 10.1182/Blood-2004-03-1001.
Fernández MN, Regidor C, Cabrera R et al. Unrelated umbilical cord blood transplants in adults: early recovery of neutrophils by supportive co-transplantation of a low number of highly purified peripheral blood CD34+ cells from an HLA-haploidentical donor. Exp Hematol 2003; 31: 535–544.
Fernández MN, Regidor C, Cabrera R et al. Dual transplants of unrelated cord blood and highly purified CD34+ cells from a related voluntary donor in adults: updated results (Eurocord-III study).– 30th Annual Meeting of the European Group for Blood and Marrow Transplantation, Barcelona, 2004. Bone Marrow Transplant 2004; 33 (Suppl 1) Abstract 320.
Rosler ES, Brandt JE, Chute J, Hoffman R . An in vivo competitive repopulation assay for various sources of human hematopoietic stem cells. Blood 2000; 96: 3414–3421.
Schiedlmeier B, Klump H, Will E et al. High-level ectopic HOXB4 expression confers a profound in vivo competitive growth advantage on human cord blood CD34+ cells, but impairs lymphomyeloid differentiation. Blood 2003; 101: 1759–1768.
Hess DA, Karanu FN, Levac K et al. Coculture and transplant of purified CD34(+)Lin(−) and CD34(−)Lin(−) cells reveals functional interaction between repopulating hematopoietic stem cells. Leukemia 2003; 17: 1613–1625.
Regidor C, Posada M, Monteagudo D et al. Umbilical cord blood banking for unrelated transplantation: evaluation of cell and storage methods. Exp Hematol 1999; 27: 380–385.
Rubinstein P, Dobrila L, Rosenfield RE et al. Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. Proc Natl Acad Sci 1995; 92: 10119–10122.
Verlinden SF, van Es HH, van Bekkum DW . Serial bone marrow sampling for long-term follow up of human hematopoiesis in NOD/SCID mice. Exp Hematol 1998; 26: 627–630.
Thiede C, Lion T . Quantitative analysis of chimerism after allogeneic stem cell transplantation using multiplex PCR amplification of short tandem repeat markers and fluorescence detection. Leukemia 2001; 15: 303–306.
Leung W, Ramirez M, Novelli EM, Civin CI . In vivo engraftment potential of clinical hematopoietic grafts. J Invest Med 1998; 46: 303–311.
Barker JN, Weisdorf DJ, Wagner JE . Creation of a double chimera after the transplantation of umbilical-cord blood from two partially matched unrelated donors. N Engl J Med 2001; 344: 1870–1871 (letter).
de Lima M, St. John LS, Wieder ED et al. Double-chimaerism after transplantation of two human leucocyte antigen mismatched, unrelated cord blood units. Br J Haematol 2002; 119: 773–776.
Barker JN, Weisdorf DJ, Defor TE et al. Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 2003; 102: 1915–1919.
Ramirez M, Rottman GA, Shultz LD, Civin CI . Mature human hematopoietic cells in donor bone marrow complicate interpretation of stem/progenitor cell assays in xenogeneic hematopoietic chimeras. Exp Hematol 1998; 26: 332–344.
Güenechea G, Segovia JC, Abella B et al. Delayed engraftment of non-obese/severe immunodeficient mice transplanted with ex-vivo expanded human CD34+ cord blood cells. Blood 1999; 93: 1097–1105.
Acknowledgements
We thank D Sánchez-Mora and Y Gutiérrez (CPH), and Jesús Martínez (CIEMAT) for technical assistance. This work was conducted as part of the Eurocord III Project and with partial support of the FIS Grant PI-03/0961.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ramírez, M., Regidor, C., Marugán, I. et al. Engraftment kinetics of human CD34+ cells from cord blood and mobilized peripheral blood co-transplanted into NOD/SCID mice. Bone Marrow Transplant 35, 271–275 (2005). https://doi.org/10.1038/sj.bmt.1704765
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1704765