A delicate balance between therapeutic cell expansion and cancer

by Alexey Bersenev on October 25, 2008 · 0 comments

in cancer, under discussion

Autologous (patient’s own) cell therapy is a very attractive model and currently works in hematology/oncology clinics. The main challenge for this therapeutic approach is to overcome a low number of stem or progenitor cells for clinically efficacious engraftment, followed by the long-term effect. Many research groups around the world try very hard to solve this problem, applying “ex vivo expansion” techniques.

Many of them can offer expansion of bone marrow hematopoietic or stromal stem or progenitor cells 10 or 30 times or even more. But do we really need that much?

Expansion is supposed to be clinically-graded, that is safe. Unfortunately a few reports suggest that ex vivo expansion of adult stem cells from rodent or human can lead to spontaneous malignant transformation.

For instance, this phenomenon was described for rat neuronal stem cells, mouse and human mesenchymal stromal progenitor cells. Nevertheless it still remains controversial, because other groups didn’t get any transformation during ex vivo expansion.

Recent study, published in Experimental Hematology add more oil in the fire. Authors show that endothelial progenitor cells (EPC), derived from human cord blood, undergo spontaneous transformation in culture even at earlier passages.

The most striking finding was that four of seven samples displayed altered karyotypes at very early passages (passage 2). Karytoype analysis performed on whole blood samples demonstrated that all samples tested were cytogenetically normal before culture, showing that the chromosomal alterations were acquired during in vitro expansion.

Control EPCs, isolated from peripheral blood, had much less expansion potential, but were karyotypically stable. Interestingly, another control – HUVEC (mature endothelial cells, isolated from umbilical cord) also showed signs of transformation – trisomy of chromosome 11.

We confirm that CB represents a good source for clinical ex vivo expansion of EPCs. However, because of high frequency of karyotype alterations, these cells cannot be considered free of risk in clinical application.

This study is only one example of adult stem/progenitor cells undergoing spontaneous malignant transformation during expansion. It shows that we need to be more careful about when to propose clinical-grade protocols of ex vivo expansion and add more safety tests (karyotyping, in vivo tumor formation assay) before starting clinical trials.

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Exp Hematol 2008;36:340

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