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Titolo:
PARTIALLY DIFFERENTIATED EX-VIVO EXPANDED CELLS ACCELERATE HEMATOLOGIC RECOVERY IN MYELOABLATED MICE TRANSPLANTED WITH HIGHLY ENRICHED LONG-TERM REPOPULATING STEM-CELLS
Autore:
SZILVASSY SJ; WELLER KP; CHEN B; JUTTNER CA; TSUKAMOTO A; HOFFMAN R;
Indirizzi:
UNIV KENTUCKY,LUCILLE P MARKEY CANC CTR,800 ROSE ST LEXINGTON KY 40536 SYSTEMIX INC PALO ALTO CA 00000
Titolo Testata:
Blood
fascicolo: 9, volume: 88, anno: 1996,
pagine: 3642 - 3653
SICI:
0006-4971(1996)88:9<3642:PDEECA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW TRANSPLANTATION; EXVIVO EXPANSION; RECONSTITUTION; EXPRESSION; INVITRO; SINGLE; GENE; PURIFICATION; PLURIPOTENT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
S.J. Szilvassy et al., "PARTIALLY DIFFERENTIATED EX-VIVO EXPANDED CELLS ACCELERATE HEMATOLOGIC RECOVERY IN MYELOABLATED MICE TRANSPLANTED WITH HIGHLY ENRICHED LONG-TERM REPOPULATING STEM-CELLS", Blood, 88(9), 1996, pp. 3642-3653

Abstract

The ability of an infusion of ex vivo expanded hematopoietic cells toameliorate cytopenia following transplantation of hematopoietic stem cells (HSCs) is controversial. To address this issue, we measured the recovery of circulating leukocytes, erythrocytes, and platelets in lethally irradiated mice transplanted with 10(3) enriched HSCs, with or without their expanded equivalent (EE) generated after 7 days of culture in interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factorand Steel Factor. Two HSC populations differing in their content of short-term repopulating progenitors were evaluated. Thy-1(lo)LIN(-)Sca-1(+) (TLS) bone marrow (BM) is enriched in colony-forming cells (CFCs), day 8 and day 12 spleen colony-forming units (CFU-S) (435+/-19, 170+/-30, and 740+/-70 per 10(3) cells, respectively), and stem cells withcompetitive long-term repopulating potential (greater than or equal to 1 per 43 cells). Thy-1(lo)Sca-1(+)H-2K(hi) cells (TSHFU) isolated from BM 1 day after treatment of donor mice with 5-fluorouracil (5-FU) are also highly enriched in competitive repopulating units (CRU, greater than or equal to 1 per 55 cells), but are depleted of CFCs, day 8 and day 12 CFU-S (171+/-8, 0 and 15+/-4 per 10(3) cells, respectively). Recipients of 10(3) TLS cells transiently recovered leukocytes to greater than or equal to 2000/mu L per L in 12 days, but sustained engraftment required 25 days. Platelets recovered to greater than or equal to200,000/mu L in 15 days, and erythrocytes never decreased below 50% of normal. Mice transplanted with 10(3) TSHFU cells recovered leukocytes in 15 days, and platelets and erythrocytes in 18 days. Recipients ofunseparated normal or 5 fU-treated BM cells (containing 10(3) TLS or TSHFU cells) recovered safe levels of blood cells in 9 to 12 days, suggesting that unseparated marrow contains early engrafting cells that were depleted by sorting, Upon ex vivo expansion, total cells, CFCs andday 12 CFU-S were amplified 2,062-, 83- and 13-fold, respectively, from TLS cells; and 1,279-, 259- and 708-fold, respectively, from TSHFU cells. Expanded cells could regenerate the majority of lymphocytes andgranulocytes in primary (17 weeks) and secondary (26 weeks) hosts andwere only moderately impaired compared to fresh HSCs. The EE of TSHFUcells was more potent than that of TLS cells, suggesting that more highly enriched HSCs are more desirable starting populations for this application. When mice were transplanted with 10(3) TSHFU cells and their EE, the duration of thrombocytopenia was shortened from 18 to 12 days, and anemia was abolished. Leukocytes were also elevated on days 9 to 12, although sustained recovery was not accelerated. Anemia was alsoabrogated in recipients of 10(3) TLS cells and their EE. Early platelet counts were slightly higher than with TLS cells alone, but leukocyte recovery was not improved. These data confirm that TLS cells contribute to early and sustained hematopoiesis, and demonstrate a benefit ofex vivo expanded cells in accelerating engraftment of more primitive TSHFU stem cells depleted of progenitors. (C) 1996 by The American Society of Hematology.

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Documento generato il 29/09/20 alle ore 15:06:20