193Use of Stem Cells for Drug Testing
With the ability to isolate, expand and study mesenchymal stem cells (MSCs)
in vitro, individual patient’s MSCs can be tested for their sensitivity to various
drugs. Potential applications are:
- Selection of individual dosing regimens based on the in vitro responsiveness in a
simple assay performed using a patient’s own MSCs. - Optimized treatment plans could then be created that effi ciently and precisely
integrate with the host’s expected biological response. - For example, a patient’s sensitivity to a specifi c dose range of parathyroid hor-
mone (PTH) could be determined in cultures of his MSCs that are induced into
the osteogenic lineage pathway.
Gene Therapy
Gene therapy is defi ned as the transfer of defi ned genetic material to specifi c target
cells of a patient for the ultimate purpose of preventing or altering a particular dis-
ease state (Jain 2015b ). It has three components; (1) identifi cation of the gene
mutated in disease and obtaining a healthy copy of that gene; (2) carrier or delivery
vehicle called vectors to deliver the healthy gene to a patient’s cells; and (3) addi-
tional DNA elements that turn on the healthy gene in the right cells and at the right
levels. The broad scope of gene therapy includes cells, which may be genetically
modifi ed to secrete therapeutic substances such as neurotrophic factors. Ex vivo
gene therapy involves the genetic modifi cation of the patient’s cells in vitro, mostly
by use of viral vectors, prior to reimplanting these cells into the tissues of the
patient’s body. This is a form of personalized therapy. Another approach to person-
alizing gene therapy for cancer would be to detect gene groups that are signifi cantly
related to a disease by conducting a series of gene expression experiments. Using
bioinformatics, gene groups emerging patterns can be analyzed to obtain the most
discriminatory genes. The discovered patterns can be used to classify new cells with
a higher accuracy than other methods. Based on these patterns, one can consider the
feasibility a personalized treatment plan which converts tumor cells into normal
cells by modulating the expression levels of a few genes.
Stem Cell-Based Personalized Gene Therapy for Cancer
Gene transfer into human hematopoietic stem cells (HSCs) enables enhancement of
anticancer immunity, whereas alteration of HSCs may increase their resistance to
cytotoxic drugs. MDR genes can be introduced into HSCs to reduce chemotoxicity
and enable the administration of higher doses of chemotherapy. Tumor cell eradica-
tion can also be enhanced by genetic modifi cation of chemosensitivity and
Gene Therapy