CELL THERAPY IN HEART DISEASES
Antonio Carlos Campos de Carvalho
Instituto de Biofı́sica Carlos Chagas Filho, UFRJ
Diretor de Pesquisa do Instituto Nacional de Cardiologia
Coordenador da Rede Nacional de Terapia Celular
Resumo/Abstract:
The use of cell therapy in medicine was established more than 40
years ago, when the first bone marrow transplants were performed.
More recently, cell therapy using bone marrow derived cells have
been the subject of intense pre-clinical and clinical investigation in
the field of cardiology. Unfortunately, despite promising initial results, clinical trials conducted under rigorous criteria have not shown
additional benefits to established therapies when using mononuclear
cells derived from the bone marrow of the cardiac patients. As a
result, scientists and clinicians have been searching for more suitable
cell types for therapy. Clinical trials are currently being conducted
using mesenchymal stem cells (MSC) derived both from bone marrow and adipose tissue, as well as stem/progenitor cells from the
heart, itself. MSC have the advantage of allogeneic use (they can be
obtained from a healthy donor for instance) and therefore can constitute an off-the-shelf product. Stem/progenitor heart cells require
cardiac biopsies, a procedure that carries risks to the patient. The
results of the clinical trials being performed with these cell types will
determine if one needs to continue the search for a more appropriate
stem cell.
The next step forward will be the use of pluripotent stem cells,
either embryonic stem cells (ESC) or induced pluripotent stem cells
(iPSC). These cells are capable of generating any cell type in our
bodies and therefore can be coaxed to differentiate into cardiomyocytes. But being able to generate the right cell type does not
guarantee a good clinical outcome. The exogenous cells still have to
survive in a hostile environment, affected by the underlying disease,
and integrate with the host tissue, thus preventing the generation
of arrhythmias and contributing to force generation by the heart
muscle. In fact, these are challenges that every cell type will have
to face in regenerative medicine.
But even if the pluripotent stem cells fail, there is one additional pathway to be pursued. Direct differentiation is a process
by which an adult cell can be transformed in a completely different adult cell type through the use of transcription factors that are
over-expressed in the original cell using gene therapy. With this
technology it has been possible to differentiate fibroblasts into neurons, cardiomyocytes, hepatocytes and blood cells. It is therefore
conceivable that cardiac fibroblasts (the cell type that proliferates
after an injury to the heart leads to cardiomyocyte death and scarring) can be transformed back into cardiomyocytes using genetic
manipulation, thus avoiding the inevitable heart failure that ensues
after a significant lesion to the heart.
In summary, the knowledge assembled during the last decade
on stem cells and cell therapies has opened undreamed possibilities
for regenerating and/or repairing our diseased organs and tissues.
Regenerative medicine will soon play an essential role in clinical
practice.
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