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Titolo:
In vitro and in vivo evidence for the long-term multilineage (myeloid, B, NK, and T) reconstitution capacity of ex vivo expanded human CD34(+) cord blood cells
Autore:
Kobari, L; Pflumio, F; Giarratana, MC; Li, XX; Titeux, M; Izac, B; Leteurtre, F; Coulombel, L; Douay, L;
Indirizzi:
Hop Armand Trousseau, Serv Hematol Biol, F-75012 Paris, France Hop Armand Trousseau Paris France F-75012 ol Biol, F-75012 Paris, France Hop St Antoine, INSERM, U417, F-75571 Paris, France Hop St Antoine ParisFrance F-75571 INSERM, U417, F-75571 Paris, France Inst Gustave Roussy, INSERM, U362, F-94805 Villejuif, France Inst Gustave Roussy Villejuif France F-94805 , F-94805 Villejuif, France Hop St Louis, Serv Rech Hematoimmunol, Paris, France Hop St Louis Paris France Louis, Serv Rech Hematoimmunol, Paris, France
Titolo Testata:
EXPERIMENTAL HEMATOLOGY
fascicolo: 12, volume: 28, anno: 2000,
pagine: 1470 - 1480
SICI:
0301-472X(200012)28:12<1470:IVAIVE>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN HEMATOPOIETIC-CELLS; CULTURE-INITIATING CELLS; COMBINED IMMUNODEFICIENT MICE; BONE-MARROW CULTURE; NOD-SCID MICE; STEM-CELLS; PROGENITOR CELLS; IN-VITRO; SELF-RENEWAL; NOD/SCID MICE;
Keywords:
ex vivo expansion; NOD-SCID; myelopoiesis assays; NK lymphopoiesis; B-lymphopoiesis; T-lymphopoiesis; CD34(+) cord blood cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Douay, L Hop Armand Trousseau, Serv Hematol Biol, 26 Ave Arnold Netter, F-75012 Paris, France Hop Armand Trousseau 26 Ave Arnold Netter Paris FranceF-75012 e
Citazione:
L. Kobari et al., "In vitro and in vivo evidence for the long-term multilineage (myeloid, B, NK, and T) reconstitution capacity of ex vivo expanded human CD34(+) cord blood cells", EXP HEMATOL, 28(12), 2000, pp. 1470-1480

Abstract

Objective. The aim of the present report is to describe clinically relevant culture conditions that support the expansion of primitive hematopoietic progenitors/stem cells, with maintenance of their hematopoietic potential as assessed by in vitro assays and the NOD-SCID in vivo repopulating capacity. Materials and Methods. CD34(+) cord blood (CB) cells were cultured in serum-free medium containing stem cell factor, Flt3 ligand, megakaryocyte growth and development factor, and granulocyte colony-stimulating factor. After 14 days, the primitive functions of expanded and nonexpanded cells were determined in vitro using clonogenic cell (colony-forming cells, long-term culture initiating cell [LTC-IC], and extended [E]-LTC-IC) and lymphopoiesis assays (NK, B, and T) and in vivo by evaluating long-term engraftment of thebone marrow of NOD-SCID mice. The proliferative potential of these cells also was assessed by determining their telomere length and telomerase activity. Results. Levels of expansion were up to 1,613-fold for total cells, 278-fold for colony-forming unit granulocyte-macrophage, 47-fold for LTC-IC, and 21-fold for E-LTC-IC. Lymphoid B-, NK, and T-progenitors could be detected. When the expanded populations were transplanted into NOD-SCID mice, they were able to generate myeloid progenitors and lymphoid cells for 5 months. These primitive progenitors engrafted the NOD-SCID bone marrow, which contained LTC-IC at the same frequency as that of control transplanted mice, withconservation of their clonogenic capacity. Moreover, human CD34(+)CD19(-) cells sorted from the engrafted marrow were able to generate CD19(+) B-cells, CD56(+)CD3(-) NR. cells, and CD4(+)CD8(+)alpha beta TCR+ T-cells in specific cultures. Our expansion protocol also maintained the telomere length in CD34(+) cells, due to an 8.8-fold increase in telomerase activity over 2 weeks of culture. Conclusions. These experiments provide strong evidence that expanded CD34() CB cells retain their ability to support long-term hematopoiesis, as shown by their engraftment in the NOD-SCID model, and to undergo multilineage differentiation along all myeloid and the B-, NK, and T-lymphoid pathways. The expansion protocol described here appears to maintain the hematopoieticpotential of CD34(+) CB cells, which suggests its relevance for clinical applications. (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 18:36:05