SIMPLE METHOD TURNS HUMAN SKIN CELLS IN TO IMMUNE STRENGTHENING WHITE BLOOD CELLS

For the first time, scientists have turned human skin cells into transplantable white blood cells, soldiers of the immune system that fight infections and invaders. The work, done at the Salk Institute, could let researchers create therapies that introduce into the body new white blood cells capable of attacking diseased or cancerous cells or augmenting immune responses against other disorders

The work, as detailed in the journal Stem Cells, shows that only a bit of creative manipulation is needed to turn skin cells into human white blood cells.

"The process is quick and safe in mice," says senior author Juan Carlos Izpisua Belmonte, holder of Salk's Roger Guillemin Chair. "It circumvents long-standing obstacles that have plagued the reprogramming of human cells for therapeutic and regenerative purposes."

Those problems includes the long time -- at least two months -- and tedious laboratory work it takes to produce, characterize and differentiate induced pluripotent stem (iPS) cells, a method commonly used to grow new types of cells. Blood cells derived from iPS cells also have other obstacles: an inability to engraft into organs or bone marrow and a likelihood of developing tumors.

The new method takes just two weeks, does not produce tumors, and engrafts well.

"We tell skin cells to forget what they are and become what we tell them to be -- in this case, white blood cells," says one of the first authors and Salk researcher Ignacio Sancho-Martinez. "Only two biological molecules are needed to induce such cellular memory loss and to direct a new cell fate."

Belmonte's team developed the faster technique (called indirect lineage conversion) and previously demonstrated that these approaches could be used to produce human vascular cells, the ones that line blood vessels. Rather than reversing cells all the way back to a stem cell state before prompting them to turn into something else, such as in the case of iPS cells, the researchers "rewind" skin cells just enough to instruct them to form the more than 200 cell types that constitute the human body.

The technique demonstrated in this study uses a molecule called SOX2 to become somewhat plastic -- the stage of losing their "memory" of being a specific cell type. Then, researchers use a genetic factor called miRNA125b that tells the cells that they are actually white blood cells.

The researchers are now conducting toxicology studies and cell transplantation proof-of-concept studies in advance of potential preclinical and clinical studies.

"It is fair to say that the promise of stem cell transplantation is now closer to realization," Sancho-Martinez says.

Study co-authors include investigators from the Center of Regenerative Medicine in Barcelona, Spain, and the Centro de Investigacion Biomedica en Red de Enfermedades Raras in Madrid, Spain.

IMMUNE CELLS PROPOSED AS HIV HIDE OUT DONT LAST IN PRIMATE MODEL

Where does HIV hide? Antiretroviral drugs can usually control the virus, but can't completely eliminate it. So any strategy to eradicate HIV from the body has to take into account not only the main group of immune cells the virus targets, called CD4 or helper T cells, but other infected cells as well.

New research from Yerkes National Primate Research Center, Emory University, sheds light on the question of which cells support viral replication and persistence, and the answers have implications for future efforts to eliminate HIV from the body in human patients.

The results were published Oct. 30 in the journal PLOS Pathogens.

"Our results have implications for efforts to cure HIV," says lead author Mirko Paiardini, PhD, assistant professor of pathology and laboratory medicine at Emory University School of Medicine and Yerkes National Primate Research Center. "Our findings suggest that therapeutic strategies aimed at stimulating infected macrophages may facilitate viral elimination."

Researchers at Yerkes looked at what happens when rhesus macaques have CD4 T cells removed from their immune systems before infection by HIV's cousin SIV. They found that another type of immune cell, called macrophages, then becomes heavily infected by SIV. Infected cells are present in lymph nodes, intestine and brain as well as in the blood.

However, the macrophages live shorter than expected based on previous research studies, which calls into question the idea that the macrophages could serve as a long-term hideout when someone is infected by HIV but receiving antiretroviral drugs.

"Among HIV researchers, there has been a lot of debate about the contribution of macrophages to the HIV reservoir," Paiardini says. "We show that in the absence of CD4 T cells, macrophages can be heavily infected by SIV, which supports a role for macrophages in viral infection. However, when infected at high levels, macrophages become short-lived cells in vivo, with an average lifespan of 1.3 days. Thus, if validated in the setting of HIV infection in humans, our data support a model in which macrophages do not constitute the long-lived reservoir (in order of weeks) that has been proposed."

The researchers also found evidence that in macaques with depleted CD4 T cells, SIV is infecting microglial cells in the brain, otherwise rarely seen.