In Vitro Proliferation and Expansion of Hematopoietic Progenitors Present in Mobilized Peripheral Blood from Normal Subjects and Cancer Patients

Abstract

In the present study, we have assessed, in a comparative manner, the in vitro proliferation and expansion potentials of hematopoietic progenitor cells (HPC) present in mobilized peripheral blood from normal subjects (MPB-n; n = 18) and cancer patients (MPB-c; n = 18). The latter included patients with breast cancer (BrCa; n = 8), Hodgkin disease (HD; n = 4), non-Hodgkin lymphoma (NHL; n = 3), and acute myeloid leukemia (AML; n = 3). Progenitor cells from normal bone marrow (BM) and umbilical cord blood (UCB) were included as controls. HPC, enriched by a negative selection procedure, were cultured for 25 days, in serum-free liquid media in the presence of a cytokine combination including early- and late-acting cytokines. Our results demonstrate that the in vitro biological properties of progenitor cells present in MPB differ, depending on whether they are derived from healthy individuals, from patients with solid tumors, or from patients with hematological neoplasias. Among all cell sources analyzed, UCB-derived progenitors showed the greatest proliferation and expansion potentials (1000-fold increase in total cell numbers on day 15, and a 22-fold increase in myeloid progenitor cell numbers, at day 10). Progenitor cells present in MPB from hematologically normal individuals showed proliferation and expansion potentials comparable to those of HPC from normal BM (500-fold increase in total cell numbers on day 15, and a 14-fold increase in myeloid progenitor cell numbers, at day 10). The proliferation/expansion potentials of MPB progenitors from BrCa patients were also within the normal range, although in the lower levels (327-fold increase in total cell numbers, on day 15, and 11.8-fold increase in myeloid progenitors, at day 10). In contrast, progenitors present in MPB from patients with HD, NHL, and especially AML, showed reduced in vitro capacities (119-, 102-, and 51-fold increase in total cell numbers, respectively; and 8-, 4-, and 2.6-fold increase in myeloid progenitor cells, respectively). To our knowledge, this is the first report in which the in vitro proliferation and expansion potentials of HPC from MPB from normal subjects and cancer patients are assessed simultaneously in a comparative manner.

Cell Cycle Differences in Vitro between Primitive Hematopoietic Cell Populations from Adult and Umbilical Cord Blood

“…In keeping with the concept mentioned earlier, we have observed that, when cultured in serumfree liquid cultures in the presence of a rich cytokine cocktail, progenitor cell-enriched Lin Ϫ cell populations derived from UCB show significantly higher in vitro growth capacities than equivalent populations from aMPB (9). The mechanisms responsible for this have not been elucidated.…”

Antitumor Effect of Lung Cancer Vaccine with Umbilical Blood Dendritic Cells in Reconstituted SCID Mice

“…Two (20 pathways of DC differentiation have been extensively studied in regard to their clinical applicability: differentiation of peripheral blood monocytes into DCs after exposure to various maturation stimuli 4,5 and differentiation of CD34 ϩ hematopoietic progenitors. 9,10,12 For therapy, autologous DCs are obtained to avoid major histocompatability complex restriction, but this is not good for the patient because the procedure requires much blood for therapy. In our study, allogeneic DCs were generated successfully from umbilical blood by culturing with GM-CSF, IL-4, and TNF-␣ and loaded with the lysate of allogeneic A549 cells.…”

“…Altering DC differentiation, maturation with low expression of activating markers like CD1a, CD40, and CD83, and longevity may be mechanisms for immune suppression. 11,12,[16][17][18] Our data have shown that AgL-DCs are capable of inducing a strong antitumor response. In our study, immunohistofluorescent stain analysis showed that CD1a ϩ and CD83 ϩ mononuclear cells markedly infiltrate the established tumors of mice treated with AgL-DCs.…”

“…The expansion potential of hematopoietic progenitor cells present in mobilized peripheral blood from patients with tumors such as Hodgkin's disease, nonHodgkin's lymphomas, and acute and myeloid leukemia showed reduced in vitro capacity. 12 These data indicate that immune cells from cancer patients may have some inherent disadvantages for immune therapy.…”

Neural Network Analysis of Ex-vivo Expansion of Hematopoietic Stem Cells

“…The network input and output data were obtained from literature 1,2,[4][5][6][7][8][9][10][11][12][14][15][16][17][18][19][20][21][22][23][24][25]27,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][46][47][48][49] for evaluation and prediction. Altogether 341 data were collected and summarized in Table 1.…”