Reserve of mesenchymal stem cells in untreated advanced breast and lung cancer patients´ bone marrow

FERNÁNDEZ VALLONE VB; MARTINEZ LM; BORDENAVE RH; CHASSEING NA

Austin, Texas.

Simposio; 5th Internacional Conference on Mesenchymal and Non Hematopoietic Stem Cells.; 2009

Texas A&M Health Science Center College of Medicine, the Scott & White Healthcare System, and the International Society for Cell Therapy (ISCT).

RESERVE OF MSCs IN UNTREATED ADVANCED BREAST AND LUNG CANCER PATIENTS´ BONE MARROWFernández Vallone Valeria B, Martínez Leandro M, Bordenave Raúl H, Chasseing Norma A.Some authors have described two different subpopulations between MSCs from bone marrow (BM), one of them of early adhesion (30 min) and the other one of late adhesion (24-48hs). The first one presents the highest self-renewal and regenerative capacity as the best regulation of hematopoiesis. In the present work we observed that untreated advanced breast and lung cancer patients (7BCP and 7LCP) had significant lower #of CFU-F (5±2 and 13±7) from the fraction of early adherence cells than healthy volunteers (7HV; 52±9). Also, we observed that BCP, LCP and HV had a #CFU-F from the fraction of late adherence = 9±3a, 14±4 and 28±6a (a=p<0,02); respectively. So the cloning efficiency of both fractions (#CFU-F/5x106 mononuclear cells) were: BCP=13±5a; LCP=26±17b and HV=80±14a,b (a,b=p<0.01). Furthermore, lower levels of Dkk-1 were released in conditioned medium (CM, 14days) of CFU-F from BCP and LCP vs HV (2,665±611; 4,276±691 and 14,484±4,034pg/ml; p=0.0002 and 0.0008), that indicate low cloning efficiency of MSCs. Also the levels of SDF-1 in CM (7 and 14 days) from CFU-F were lower in BCP and LCP than HV (pg/ml,7d = 42±6; 46±6 and 83±10, p=0.001 and 0.0038; 14d: 89±17; 74±5 and 263±60, p=0.048 and 0.0064). SDF-1 is recently related in the improvement of cloning capacity, positive hematopoiesis regulation by forming an effective stroma, migratory capacity and multipotentiality of MSCs. Finally we observed higher levels of PDGF-AB, MSC migration factor, in BM-plasma of BCP and LCP vs HV (pg/ml= 4,468±746; 7,268±1,366 vs 2,528±429, p<0,05 and 0,01).In conclusion, BCP and LCP presented a decrease number of early adherent BM-MSCs, data related to the minor release of Dkk-1 and SDF-1. In addition as the number of CFU-F represents the number of MSC in vivo, may be at this time of the tumor development early adherent MSCs (highest regenerative capacity) have migrated to the primitive tumor so the medullar reserve of this subpopulation of MSCs is minimal.