Plasticity of mesenchymal stem cell from bone marrow of patients with lung and breast cancer.

HOFER EL,; HERNANDO INSÚA A.; FERNÁNDEZ VALLONE V.; FELDMAN L,; BORDENAVE RH,; CHASSEING NA.

Buenos Aires, Argentina.

Jornada; VIII Jornadas Multidisciplinarias de la Sociedad Argentina de Biología.; 2006

Sociedad Argentina de Biología.

PLASTICITY OF MESENCHYMAL STEM CELL (MSC) FROM BONE MARROW (BM) OF PATIENTS WITH LUNG AND BREAST CANCER. MSC are able to self-renewal and to differentiate. MSC form fibroblast colonies (CFU-F) when grown in FBS. Previously, we observed a decrease of the cloning efficiency of MSC to give CFU-F, and of the CFU-F size in BM of untreated advanced breast and lung cancer patients (BCP and LCP) vs.  normal volunteers (NV).Proliferative activity of NV-MSC is directly proportional to their multipotentialy. In order to study the influence of tumor development on the relationship between self-renew and plasticity of MSC, we evaluated the osteochondroadipogenic differentiation of MSC on 7 BM chemonaive advanced BCP, 7 LCP and 7 NV. MSC derived from low density 3rd passage were cultured for 21 days in osteogenic, adipogenic, or chondrogenic medium. Cells were stained with Giemsa, Von-Kossa, Alizarin Red, OilRed-O and Toludine blue (TB). Immunocytochemistry for osteocalcin and type II collagen were done. We also characterized the cells into a pattern from grade 0 to 3; 0=fibroblast like, 1=in the way to osteoblast, 2=osteoblast, 3=osteocyte.Adipogenic:100% NV cultures responded achieving morphologies with characteristics of this linage vs. 57% BCP and LCP. # adipocytes/petri dish (X±SE):NV=468±215a, b; LCP=98±66a; BCP=4± 3b(Mann Whitney: a=p< 0,03; b=p< 0,001).Chondrogenic:all cultures developed chondrogenic pellets. +TB staining with chondrocyte-like lacunae and aggrecan-rich extracellular matrix (EM) were evident in histological sections, and type II collagen-rich EM. An increase of chondrocytes/pellet was seen in patients versus NV (LCP and BCP vs. NV =p<0,026 and <0,002, Mann Whitney).Osteogenic:patient´s cultures showed a 15±7 (BCP) and 10±3% (LCP) of cells differentiated vs. 24±4% of NV. 43%NV cultures achieved grade 1 and 57% grade 2-3.In BCP, 57% of the cultures differentiate. From these ones the 75% reached grade 1 and 25% grade 2-3. Grade 1 was achieved by 6/7 LCP cultures and the other grade 3. Patients showed heterogeneous distribution of calcium as well as an inadequate mineralization of EM. All cultures showed a weak expression of osteocalcin. Results showed that BCP and LCP-BM had a high % of small renewing MSC, which gave small CFU-F and had less osteoadipogenic potential.