Biomedical subjects

L Douay

Publications and source records attributed to L Douay.

111 records · Page 7Linked to original sources

PubMedDate not supplied

[From control of hematopoiesis to cellular therapy: the perspectives for transfusion].

The ability to identify, select and manipulate stem cells from tissues opens the way to regenerative medicine. In the field of hematopoiesis, our increasingly precise knowledge of the mechanisms of production and regulation of blood cells should permit in the near future the production of cells in sufficient quantity to be of interest for transfusion. Our present capacity to amplify hematopoietic stem cells and direct their differentiation towards the erythroid line is reviewed here. A procedure is described for the amplification of CD34 + hematopoietic stem cells of placental origin, based on the sequential use of specific combinations of growth factors in a given serum-free medium. Such conditions allowing the terminal maturation in vivo of large numbers of precursors produced ex vivo permit one to envisage important transfusion perspectives. A complementary source of red blood cells would in fact improve our transfusion capacity.

Animals↗

PubMedDate not supplied

[Autologous bone marrow graft in the initial treatment of follicular lymphomas in young high risk subjects. A new therapeutic approach].

Low grade malignant follicular lymphoma is characterized by its slow course over many years. However, despite a median survival of 4 to 8 years the cure rate is lower than 10 percent and even nil for some authors. The best therapeutic approach of the disease is unknown, and many teams of oncologists are in favour of a more intense chemotherapy. We present a study of 10 patients selected for their young age and for the presence of detrimental prognostic factors (index 3 of Coiffier's classification in 8/10 patients). Nine patients received BCNU, cytosine arabinoside, etoposide and melphalan, followed by reinjection of autologous bone marrow purged in vitro by mafosfamide in the adjusted dose CFUGM LD 95. Eight of these 9 patients are in complete, unmaintained remission 15 to 43 months after the bone marrow transplantation (including 3 patients in a more than 2 years' remission). The 10th patient had autologous bone marrow transplantation in 1979; after treatment with heavy TACC chemotherapy followed by reinjection of unpurged bone marrow, he remained in complete remission for 9 years, then relapsed; he is now alive with a progressive tumour. Although the follow-up was relatively short for a particularly slow disease, this study shows that, owing to autologous bone marrow transplantation as early as the first complete remission, one of the heaviest types of chemotherapy can be delivered in patients with non-Hodgkin's lymphoma, unless precluded by toxicity. At the moment, this protocol is experimental and can be used only in young subjects at high risk. Further studies on larger series of patients and with a longer follow-up are needed to evaluate the effectiveness of this new type of treatment compared with conventional chemotherapies.

Adult↗

PubMedDate not supplied

The potential role of FLT3 ligand in progenitor and primitive hematopoietic cell expansion.

We have previously defined the experimental conditions for hematopoietic cell expansion. CD34+ human marrow cells were maintained in a serum-free, stroma-free liquid culture system, at a concentration of 10(3) cells/ml, for 10 days at 37 degrees C, in the presence of various cytokine combinations. The basic combination of early cytokines SCF (100 ng/ml), IL3 (5 ng/ml), IL6 (10 ng/ml), has a modest stimulating effect on all compartments: the number of total cells increased 56-fold and CD34+ cells 1-fold; CFU-GM, BFU-E and CFU-MK, increased 6-fold, 5-fold and 3-fold respectively. As far as CD34+ cells are concerned, the subpopulation CD34+/CD38- was only maintained. Interestingly, the addition of 100 ng/ml of Flt3 ligand (FL) significantly enhanced the amplification of total cells (276-fold), CFU-GM (54-fold) and BFU-E (15-fold). The number of CD34+ cells and the subpopulation CD34+/38- increased to 7-fold and 22-fold respectively. Moreover, long term culture-initiating cells (LTC-ICs) in limiting dilution assay (LDA) were found to increase 3-fold. Further addition of MGDF (10 ng/ml), G-CSF (10 ng/ml) and Epo (0.5 U/ml), in various combinations, acted synergically with the previous cytokine combination to support the formation of multiple types of hematopoietic colonies. As expected, the addition of MGDF increased the number of CFU-MK up to 5-fold expansion. Interestingly, MGDF addition was synergistic also for BFU-E and CFU-GM expansion. In the combination of SCF+ IL3+ IL6+ FL + MGDF, CFU-GM expanded to 73-fold and BFU-E to 17-fold. G-CSF in SCF + IL3 + IL6 + FL conditions stressed the expansion of the granulopoietic compartment doubling the number of CFU-GM and CD33+ cells, with no consequence on LTC-IC or BFU-E. Surprisingly, G-CSF induced the expansion of the megakaryocytic lineage up to 6-fold, in a similar way as MGDF. Epo in presence of SCF+ IL3+ IL6+/-FL dramatically increased total cell expansion (2300-2800-fold), mainly erythroblastic (70% glycoA) without exhaustion of all other compartments. The simultaneous use of these three cytokines (MGDF + G-CSF + Epo) in presence of four early cytokines (SCF + IL3 + IL6 + FL) clearly allows a significant expansion of all hematopoietic compartments, precursors, progenitors, and primitive stem cells. In conclusion, these data show the ability of a stroma-free, serum-free liquid system to expand all myeloid lineages, including CFU-MK and LTC-IC which are critical for clinical application of ex vivo expanded cells.

Colony-Forming Units Assay↗