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infection in iPSC-derived liver
cells 8 days after infection
Credit: Shengyong Ng et al.
Researchers say they’ve found a way to grow liver-like cells from induced pluripotent stem cells (iPSCs).
The liver-like cells can be infected with several strains of the malaria parasite and respond to existing drugs the same way mature human liver cells do.
The new cells, described in Stem Cell Reports, could allow scientists to test drugs on cells from people with different genetic backgrounds, who may respond differently to malaria infection and treatment.
Modeling infection
Until now, malaria researchers have not had many reliable ways to test new drugs in liver tissue.
“What’s historically been done is people have tried to make do with the systems that were available,” said study author Sangeeta Bhatia, MD, PhD, of the Massachusetts Institute of Technology in Cambridge.
In 2013, Dr Bhatia and her colleagues showed they could model malaria infection in hepatocytes from human donors. However, this generates only a limited supply from each donor, and not all of the cells work well for drug studies.
The researchers then turned to iPSCs, which can be generated from human skin cells by adding reprogramming factors. To create liver cells, the researchers added a series of growth factors, including hepatocyte growth factor, to the iPSCs.
The team generated these cells in 2012 and used them to model infection of hepatitis C. However, these cells, known as hepatocyte-like cells, did not seem to be as mature as real adult liver cells.
In the current study, the researchers found these cells could be infected with several strains of malaria. But, initially, the cells did not respond to drugs in the same way as adult liver cells.
In particular, they were not sensitive to primaquine, which works only if cells have a certain set of drug-metabolism enzymes found in mature liver cells.
To induce the cells to become more mature and turn on these metabolic enzymes, the researchers added a molecule they had identified in a previous study. This compound, which the researchers call a “maturin,” stimulated the cells to turn on those enzymes, which made them sensitive to primaquine.
Toward better drugs
The team is now working with the nonprofit foundation Medical Malaria Ventures to test about 10 potential malaria drugs that are in the pipeline, first using adult donor liver cells and then the hepatocyte-like cells generated in this study.
These cells could also prove useful to help identify new drug targets, the researchers said. In this study, they found the liver-like cells can be infected with malaria when they are still in the equivalent of fetal stages of development, when they become hepatoblasts, which are precursors to hepatocytes.
In future studies, the researchers plan to investigate which genes get turned on when the cells become susceptible to infection, which may suggest new targets for malaria drugs.
They also hope to compare the genes needed for malaria infection with those needed for hepatitis infection, in hopes of identifying common pathways to target for both diseases. 
infection in iPSC-derived liver
cells 8 days after infection
Credit: Shengyong Ng et al.
Researchers say they’ve found a way to grow liver-like cells from induced pluripotent stem cells (iPSCs).
The liver-like cells can be infected with several strains of the malaria parasite and respond to existing drugs the same way mature human liver cells do.
The new cells, described in Stem Cell Reports, could allow scientists to test drugs on cells from people with different genetic backgrounds, who may respond differently to malaria infection and treatment.
Modeling infection
Until now, malaria researchers have not had many reliable ways to test new drugs in liver tissue.
“What’s historically been done is people have tried to make do with the systems that were available,” said study author Sangeeta Bhatia, MD, PhD, of the Massachusetts Institute of Technology in Cambridge.
In 2013, Dr Bhatia and her colleagues showed they could model malaria infection in hepatocytes from human donors. However, this generates only a limited supply from each donor, and not all of the cells work well for drug studies.
The researchers then turned to iPSCs, which can be generated from human skin cells by adding reprogramming factors. To create liver cells, the researchers added a series of growth factors, including hepatocyte growth factor, to the iPSCs.
The team generated these cells in 2012 and used them to model infection of hepatitis C. However, these cells, known as hepatocyte-like cells, did not seem to be as mature as real adult liver cells.
In the current study, the researchers found these cells could be infected with several strains of malaria. But, initially, the cells did not respond to drugs in the same way as adult liver cells.
In particular, they were not sensitive to primaquine, which works only if cells have a certain set of drug-metabolism enzymes found in mature liver cells.
To induce the cells to become more mature and turn on these metabolic enzymes, the researchers added a molecule they had identified in a previous study. This compound, which the researchers call a “maturin,” stimulated the cells to turn on those enzymes, which made them sensitive to primaquine.
Toward better drugs
The team is now working with the nonprofit foundation Medical Malaria Ventures to test about 10 potential malaria drugs that are in the pipeline, first using adult donor liver cells and then the hepatocyte-like cells generated in this study.
These cells could also prove useful to help identify new drug targets, the researchers said. In this study, they found the liver-like cells can be infected with malaria when they are still in the equivalent of fetal stages of development, when they become hepatoblasts, which are precursors to hepatocytes.
In future studies, the researchers plan to investigate which genes get turned on when the cells become susceptible to infection, which may suggest new targets for malaria drugs.
They also hope to compare the genes needed for malaria infection with those needed for hepatitis infection, in hopes of identifying common pathways to target for both diseases.
infection in iPSC-derived liver
cells 8 days after infection
Credit: Shengyong Ng et al.
Researchers say they’ve found a way to grow liver-like cells from induced pluripotent stem cells (iPSCs).
The liver-like cells can be infected with several strains of the malaria parasite and respond to existing drugs the same way mature human liver cells do.
The new cells, described in Stem Cell Reports, could allow scientists to test drugs on cells from people with different genetic backgrounds, who may respond differently to malaria infection and treatment.
Modeling infection
Until now, malaria researchers have not had many reliable ways to test new drugs in liver tissue.
“What’s historically been done is people have tried to make do with the systems that were available,” said study author Sangeeta Bhatia, MD, PhD, of the Massachusetts Institute of Technology in Cambridge.
In 2013, Dr Bhatia and her colleagues showed they could model malaria infection in hepatocytes from human donors. However, this generates only a limited supply from each donor, and not all of the cells work well for drug studies.
The researchers then turned to iPSCs, which can be generated from human skin cells by adding reprogramming factors. To create liver cells, the researchers added a series of growth factors, including hepatocyte growth factor, to the iPSCs.
The team generated these cells in 2012 and used them to model infection of hepatitis C. However, these cells, known as hepatocyte-like cells, did not seem to be as mature as real adult liver cells.
In the current study, the researchers found these cells could be infected with several strains of malaria. But, initially, the cells did not respond to drugs in the same way as adult liver cells.
In particular, they were not sensitive to primaquine, which works only if cells have a certain set of drug-metabolism enzymes found in mature liver cells.
To induce the cells to become more mature and turn on these metabolic enzymes, the researchers added a molecule they had identified in a previous study. This compound, which the researchers call a “maturin,” stimulated the cells to turn on those enzymes, which made them sensitive to primaquine.
Toward better drugs
The team is now working with the nonprofit foundation Medical Malaria Ventures to test about 10 potential malaria drugs that are in the pipeline, first using adult donor liver cells and then the hepatocyte-like cells generated in this study.
These cells could also prove useful to help identify new drug targets, the researchers said. In this study, they found the liver-like cells can be infected with malaria when they are still in the equivalent of fetal stages of development, when they become hepatoblasts, which are precursors to hepatocytes.
In future studies, the researchers plan to investigate which genes get turned on when the cells become susceptible to infection, which may suggest new targets for malaria drugs.
They also hope to compare the genes needed for malaria infection with those needed for hepatitis infection, in hopes of identifying common pathways to target for both diseases.