Monday, 1 April 2013

Researchers use Cytomegalovirus strategy to "fortify" mesenchymal stem cells

In a study released a few days ago, researchers from the Wake Forest Baptist Medical Centre's Institute for Regenerative Medicine have presented a new method that makes allogeneic mesenchymal stem cells (MSCs) invisible to the host's immune system. The method involves the use of a strategy normally employed by the human cytomegalovirus (HCMV) which, when used on MSCs, helps them avoid the immune system, greatly enhancing their healing potential.

As indicated by many studies, MSCs have the capacity to treat a wide variety of conditions and diseases by regenerating damaged tissue. However, in non-autologous transplantations, they are susceptible to being attacked and killed by the host's immune system. According to Graca Almeida-Porada, senior author of the study, he and his team have created a new type of MSCs that are "invisible" to the cells of immune system (like natural killer cells and T-cells). This ability allows them to survive longer, giving them more time to promote healing.

"These cells have a natural ability to help modulate the immune response, so if we can increase their survival, they theoretically could be a therapy to decrease inflammation and help transplant patients avoid organ rejection," said Almeida-Porada.

To do so the researchers took advantage of the HCMV's ability to avoid the human immune system. HCMV is a relatively harmless virus which infects about 40 % of the total population (50% to 80% in U.S adults). HCMV is generally asymptomatic, remaining latent for long periods of time.


Anatomy of a CMV virus
Scheme of a HCMV Virus


"Our strategy was to modify the cells to produce the same proteins as the HCMV virus so they could escape death and help modulate inflammation and promote healing." said Almeida-Porada.

During the study, the researchers first extracted MSCs from human fetal liver tissue, obtained by Advanced Bioscience Resources. Then, they modified these stem cells, forcing them to express certain HMCV proteins and found, for the first time, that MSCs overexpressing the US2 protein have an increased cell survival by 59 percent when compared to normal mesenchymal stem cells.

The researchers now aim to assess the efficacy of these stem cells in the treatment of numerous conditions including "bowel disease, traumatic brain injury and human organ transplant".


 Video about the human cytomegalovirus


Reference
Soland, M., Bego, M., Colletti, E., Zanjani, E., St. Jeor, S., Porada, C., & Almeida-Porada, G. (2013). Mesenchymal Stem Cells Engineered to Inhibit Complement-Mediated Damage PLoS ONE, 8 (3) DOI: 10.1371/journal.pone.0060461

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