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Eyrich M, Schreiber SC, Wollny G, Ziegler H, Schlenker R, Koch-Büttner K, Wölfl M, Schlegel PG, Schilbach K. Author information 1 Stem Cell Laboratory, University Children's Hospital Würzburg, Würzburg, Germany. Eyrich_m@klinik.uni-wuerzburg.de Abstract T-cell re-constitution after allogeneic stem cell transplantation (alloSCT) is often dampened by the slow differentiation of human peripheral blood CD34(+) (huCD34(+) ) hematopoietic stem cells (HSCs) into mature T cells. This process may be accelerated by the co-transfer of in vitro-pre-differentiated committed T/NK-lymphoid progenitors (CTLPs). Here, we analysed the developmental potential of huCD34(+) HSCs compared with CTLPs from a third-party donor in a murine NOD-scid IL2Rγ(null) model of humanised chimeric haematopoiesis. CTLPs (CD34(+) lin(-) CD45RA(+) CD7(+) ) could be generated in vitro within 10 days upon co-culture of huCD34(+) or cord blood CD34(+) (CB-CD34) HSCs on murine OP9/N-DLL-1 stroma cells but not in a novel 3-D cell-culture matrix with DLL-1(low) human stroma cells. In both in vitro systems, huCD34(+) and CB-CD34(+) HSCs did not give rise to mature T cells. Upon transfer into 6-wk-old immune-deficient mice, CTLPs alone did not engraft. However, transplantation of CTLPs together with huCD34(+) HSCs resulted in rapid T-cell engraftment in spleen, bone marrow and thymus at day 28. Strikingly, at this early time point mature T cells originated exclusively from CTLPs, whereas descendants of huCD34(+) HSCs still expressed a T-cell-precursor phenotype (CD7(+) CD5(+) CD1a(+/-) ). This strategy to enhance early T-cell re-constitution with ex vivo-pre-differentiated T-lymphoid progenitors could bridge the gap until full T-cell recovery in severely immunocompromised patients after allogeneic stem cell transplantation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. PMID: 21928276 DOI: 10.1002/eji.201141561 [Indexed for MEDLINE] Free full text Share on FacebookShare on TwitterShare on Google+ Publication type, MeSH terms LinkOut - more resources Supplemental Content Full text links Icon for Wiley Save items View more options Similar articles Charac
Pre-differentiated human committed T-lymphoid progenitors promote peripheral T-cell re-constitution after stem cell transplantation in immunodeficient mice.
Eur J Immunol
2011
41(12):3596-603
PubMed ID: 21928276
DOI: 10.1002/eji.201141561
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