Bone Marrow Transplantation (2010) 45, 1661–1662 & 2010 Macmillan Publishers Limited All rights reserved 0268-3369/10
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LETTER TO THE EDITOR
SDF-1/CXCR4 blockade to mobilize hematopoietic progenitor cells from the placenta Bone Marrow Transplantation (2010) 45, 1661–1662; doi:10.1038/bmt.2010.22; published online 22 February 2010 Umbilical cord blood has been introduced as an alternative graft source for allogeneic hematopoietic SCT in both pediatric and adult patients. However, the limited number of hematopoietic stem cells (HSC) leads to delayed engraftment, especially in adult recipients.1 Therefore, several groups are working on an optimized collection procedure in order to increase the number of transplantable progenitors. Bornstein et al.2 have demonstrated recently that a modified in utero/ex utero two-step collection procedure can lead to a significant increase in the number of harvested progenitor cells. Especially in patients with a limited hematopoietic capacity, the bicyclam AMD3100, a CXCR4 antagonist, in combination with G-CSF is able to induce a significant mobilization of CD34 þ cells.3 Dipersio et al. have already shown that AMD3100 may provide an alternative method of HSC mobilization even in allogeneic donors.4 Gene expression data indicate that AMD3100-mobilized HSCs may represent a functionally different subset of HSCs.5 As demonstrated for the BM niche, the homing of HSC to the placenta is probably also mediated by the expression of SDF-1.6 Recently, Serikov et al.7 could demonstrate that AMD3100 is able to mobilize additional HSC from the placenta by perfusion of the placenta for up to 6 h. Within a pilot study, we could confirm Serikov’s data indicating that AMD3100 is able to mobilize hematopoietic progenitor cells from the placenta. First we obtained cord blood samples using standard techniques ex utero after delivery of the placenta. After the blood flow had ceased, we flushed the placental vessels with 30 ml of 0.9% saline and 10% ACD to collect the remaining cord blood (saline wash). The proportions of CD34 þ and CD133 þ cells in ‘saline wash’ (CD34 þ : 0.13±0.03%; CD133 þ : 0.05±0.02%) were not significantly different from those in the primary cord blood samples. Then we flushed the placental vessels again with Table 1 Comparison of the primary cord blood collection, AMDmobilized cells and control (incubation with saline without AMD3100 for 30 min) Cord blood Volume (ml) 50±8.4 Cell count ( 108) 6.20±1.12 CD34+% 0.14±0.03% CD133+% 0.09±0.02% N (placenta number) 9
AMD mobilization
Control
28±2.0 0.45±0.12 0.28±0.07% 0.17±0.04% 9
30±2.0 0.34±0.05 0.10±0.01% 0.08±0.01% 4
30 ml of 0.9% saline supplemented with 10 mg/ml AMD3100. After 30 min of incubation, the instilled solution was eluted. No clotting was detected. Despite the lower cell concentration in the recollected elution, fluorescence-activated cell sorting (FACS) revealed a significant increase (P ¼ 0.01) in the proportion of CD34 þ and CD133 þ cells compared with cord blood samples in nine consecutive placenta studies, as shown in Table 1. The total number of CD34 þ cells recovered in 28 ml of rinsing solution containing AMD3100 was 0.13±0.034 106. Whether this number of transplantable HSC is clinically meaningful remains to be studied. As control, the placenta was incubated with 0.9% saline without AMD3100 for 30 min. No increase in the CD34 þ or CD133 þ cell count was detectable (Table 1). In summary, our preliminary data demonstrate that the CXCR4 antagonist AMD3100 mobilizes placenta- derived CD34 þ cells ex utero already after 30 min of incubation, and may further enhance the efficacy of harvesting placenta-derived HSC.
Conflict of interest The authors declare no conflict of interest.
Acknowledgements This work was sponsored by DFG grant ‘Collaborative Research Center 655’: Cells into tissues: stem cell and progenitor commitment and interactions during tissue formation (SFB 655, Dresden).
D Jing1, N Alakel1, M Bornha¨user, G Ehninger and R Ordemann Medical Clinic and Policlinic I, University Hospital, Dresden, Germany E-mail:
[email protected] 1 These authors contributed equally to this work.
References 1 Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 2004; 351: 2276–2285. 2 Bornstein R, Flores AI, Montalban MA, del Rey MJ, de la SJ, Gilsanz F. A modified cord blood collection method achieves sufficient cell levels for transplantation in most adult patients. Stem Cells 2005; 23: 324–334.
Letter to the Editor
1662 3 Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med 2005; 201: 1307–1318. 4 Devine SM, Vij R, Rettig M, Todt L, McGlauchlen K, Fisher N et al. Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood 2008; 112: 990–998. 5 Fruehauf S, Seeger T, Maier P, Li L, Weinhardt S, Laufs S et al. The CXCR4 antagonist AMD3100 releases a subset of G-CSF-primed peripheral blood progenitor cells with
Bone Marrow Transplantation
specific gene expression characteristics. Exp Hematol 2006; 34: 1052–1059. 6 Faye A, Pornprasert S, Dolcini G, Ave P, Taieb J, Taupin JL et al. Evaluation of the placental environment with a new in vitro model of histocultures of early and term placentae: determination of cytokine and chemokine expression profiles. Placenta 2005; 26: 262–267. 7 Serikov V, Hounshell C, Larkin S, Green W, Ikeda H, Walters MC et al. A brief communication: human term placenta as a source of hematopoietic cells. Exp Biol Med 2009; 234: 813–823.
