| RRC ID |
61945
|
| 著者 |
Eyrich M, Schreiber SC, Wollny G, Ziegler H, Schlenker R, Koch-Büttner K, Wölfl M, Schlegel PG, Schilbach K.
|
| タイトル |
Pre-differentiated human committed T-lymphoid progenitors promote peripheral T-cell re-constitution after stem cell transplantation in immunodeficient mice.
|
| ジャーナル |
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.
|
| 巻・号 |
41(12)
|
| ページ |
3596-603
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
OP9/N-DLL1(RCB2927) |
