Gene marker may improve odds of stem cell therapies for disease

Jan 7 2009

A single tumor-suppressor gene may provide a unique marker for senescence in Mesenchymal stem cells (MSCs) in vitro, while also playing a role in moving MSCs into senescence, researchers at the Human Health Foundation and the Sbarro Institute for Cancer Research and Molecular Medicine report.

Their work was published in Stem Cells and Development .

The finding is important, since MSCs are currently being tested in cell and gene therapy for a number of human diseases.

When injected into the body, MSCs have the unique ability to differentiate into a variety of cells. But before they can be employed for therapeutic uses, the stem cells must be cultivated in vitro. During this process, MSCs are often compromised when they enter senescence, or aging, which limits their capacity to proliferate and differentiate into new tissues, making them useless for treatment.

In the current study, researchers studied senescent MSCs drawn from rats in vitro. MSCs in senescence showed a downregulation, or decrease, in several genes involved in stem cell self-renewal and DNA repair, including Rb1 and p107 gene expression.

However, pRB2/p130, a tumor suppressor gene first identified by Antonio Giordano, Director of the Sbarro Institute for Cancer Research and Molecular Medicine at the College of Science and Technology at Temple University and a "Chiara Fama" Professor at the University of Siena, Italy, and a co-author of the paper, became the prominent RB protein.

"By studying the process of senescence in MSCs we have arrived at new possibilities to improve the therapeutic capabilities of the stem cells in transplantation," said Giordano.

"The presence of Rb2 during senescence raises the possibility it may provide an early marker of the process," said co-author Umberto Galderisi, a Professor at the University of Naples and an Adjunct Associate Professor at the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University. "Next we will work to confirm our data by seeing the impact when Rb2 is silenced in these stem cells."

The Human Health Foundation (HHF) (www.hhfonlus.org) is a nonprofit organization designed to develop and fund biomedical research in Italy. Along with developing new medical research centers, HHF promotes and supports novel methods for the prevention, diagnosis and treatment of cancer and other illnesses; implements and designs new initiatives to exchange and spread the results of new research; and design original programs to inform and increase public awareness of health and research issues.

Sbarro Health Research Organization (www.shro.org), a leader in cancer, cardiovascular, and diabetes research, a nonprofit charitable organization, supports the Sbarro Institute for Cancer Research and Molecular Medicine located at Temple University in Philadelphia.