REMOVAL OF CARCINOMA-CELLS FROM CONTAMINATED BONE-MARROW USING THE LIPOPHILIC CATION RHODAMINE-123

Autologous bone marrow transplants for solid tumor treatment are sever ely limited by the potential presence of residual cancer cells in the reinfused bone marrow and can lead to future tumor recurrence. This ar ticle presents a novel method of removing carcinoma cells from bone ma rrow with contaminating cancer cells, This method is based on our prev ious studies demonstrating that carcinoma cells have a higher uptake o f lipophilic cations such as rhodamine 123 than their normal epithelia l counterparts, When the relative differences in rhodamine 123 uptake are quantified, carcinoma cell lines demonstrated a 7.4-21 times great er uptake of rhodamine 123 than normal mouse bone marrow cells, More i mportant, when normal bone marrow cells and carcinoma cell lines are m ixed to simulate carcinoma-contaminated bone marrow, individual cell p opulations continue to exhibit characteristic and identifiable relativ e differences (10-20 times) in rhodamine 123 uptake, Differential sort ing of bone marrow/carcinoma cell mixtures with respect to rhodamine 1 23 fluorescence intensity resulted in the removal of 95-99% of the ''c ontaminating carcinoma cells.'' The recovered bone marrow cells were f ully viable as ascertained by their ability to form splenic colonies. In our preliminary experiments, sorted bone marrow cells transplanted into lethally irradiated C57BL6 mice allowed the mice to survive for m ore than 8 months, Tn light of these promising results, we propose tha t lipophilic cations may play a role in the purification of autologous bone marrow used in transplants for patients with advanced solid tumo rs.