Reference - Detail
| RRC ID | 61945 |
|---|---|
| Author | Eyrich M, Schreiber SC, Wollny G, Ziegler H, Schlenker R, Koch-Büttner K, Wölfl M, Schlegel PG, Schilbach K. |
| Title | Pre-differentiated human committed T-lymphoid progenitors promote peripheral T-cell re-constitution after stem cell transplantation in immunodeficient mice. |
| Journal | Eur J Immunol |
| 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. |
| Volume | 41(12) |
| Pages | 3596-603 |
| Published | 2011-12-1 |
| DOI | 10.1002/eji.201141561 |
| PMID | 21928276 |
| MeSH | Animals Cell Differentiation / immunology Cells, Cultured Coculture Techniques Fetal Blood / immunology Hematopoiesis / immunology Hematopoietic Stem Cell Transplantation* Humans Lymphoid Progenitor Cells / cytology Lymphoid Progenitor Cells / immunology* Mice Mice, Inbred NOD Mice, SCID Stromal Cells / immunology T-Lymphocytes / cytology T-Lymphocytes / immunology* |
| IF | 4.404 |
| Altmetric score |
オルトメトリクス指標項目
|
| Total number of mentions | 0 |
| Resource | |
| Human and Animal Cells | OP9/N-DLL1(RCB2927) |