To improve patient care and outcomes, leading dermatologists offered their recommendations on the top scar treatments. Consideration must be given to:

Cutis invites readers to send us their recommendations. Over-the-counter antifungals, antiperspirants, and sunless tanners will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on the top scar treatments. Consideration must be given to:

Cutis invites readers to send us their recommendations. Over-the-counter antifungals, antiperspirants, and sunless tanners will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on the top scar treatments. Consideration must be given to:

Cutis invites readers to send us their recommendations. Over-the-counter antifungals, antiperspirants, and sunless tanners will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

Subclonal populations in an

MM patient, represented as

different colored cells

Credit: Lauren Solomon

Results of a new study suggest the genetic landscape of multiple myeloma (MM) may be more complex than we thought.

The research revealed “widespread” heterogeneity in samples from more than 200 MM patients.

In some cases, a single patient had multiple mutations in the same pathway. And most of the patients harbored at least 3 detectable subclonal mutations.

The researchers said these findings, published in Cancer Cell, might explain why targeted therapies are not always effective in MM and why some patients relapse after treatment.

“What this new work shows us is that when we treat an individual patient with multiple myeloma, it’s possible that we’re not just looking at one disease, but at many,” said study author Todd Golub, MD, of the Dana-Farber Cancer Institute in Cambridge, Massachusetts.

“In the same person, there could be cancer cells with different genetic make-ups. These findings indicate a need to identify the extent of genetic diversity within a tumor as we move toward precision cancer medicine and genome-based diagnostics.”

Dr Golub and his colleagues studied samples from 203 MM patients and identified frequent mutations in genes known to play an important role in MM, including KRAS, NRAS, and BRAF.

But many of these telltale mutations were not present in all MM cells. Instead, they were often observed only in a subclonal population.

This suggests targeted therapies may have limitations in patients whose tumors are made up of these subclonal populations, the researchers said.

To explore the therapeutic implications of this research, the team performed follow-up experiments looking specifically at BRAF, a gene for which several inhibitors exist.

Previous studies indicated that roughly 4% of MM patients may have mutations in this gene. And a recent report on a single MM patient treated with drugs targeting BRAF showed promising results.

However, Dr Golub and his colleagues found evidence that treating a tumor harboring subclonal BRAF mutations with one of these agents may, at best, kill a fraction of the cells and, at worst, stimulate another cancer cell subpopulation to grow.

“There’s clearly potential for these drugs in some patients with multiple myeloma, but we show that there are also potential problems for others,” said study author Jens Lohr, MD, PhD, also of Dana-Farber.

“If a patient has a BRAF mutation in less than 100% of his cells, or if he has mutations in KRAS or NRAS at the same time, [it] may influence the response to an inhibitor.”

This suggests subclonal populations could be one of the reasons many patients suffer relapse after treatment, the researchers said.

“Matching the right drug to the right patient may not be as easy as finding a mutation and having a drug that targets it,” Dr Lohr said. “We have to keep this additional parameter of heterogeneity in mind and keep exploring what it means for therapy.”

Subclonal populations in an

MM patient, represented as

different colored cells

Credit: Lauren Solomon

Results of a new study suggest the genetic landscape of multiple myeloma (MM) may be more complex than we thought.

The research revealed “widespread” heterogeneity in samples from more than 200 MM patients.

In some cases, a single patient had multiple mutations in the same pathway. And most of the patients harbored at least 3 detectable subclonal mutations.

The researchers said these findings, published in Cancer Cell, might explain why targeted therapies are not always effective in MM and why some patients relapse after treatment.

“What this new work shows us is that when we treat an individual patient with multiple myeloma, it’s possible that we’re not just looking at one disease, but at many,” said study author Todd Golub, MD, of the Dana-Farber Cancer Institute in Cambridge, Massachusetts.

“In the same person, there could be cancer cells with different genetic make-ups. These findings indicate a need to identify the extent of genetic diversity within a tumor as we move toward precision cancer medicine and genome-based diagnostics.”

Dr Golub and his colleagues studied samples from 203 MM patients and identified frequent mutations in genes known to play an important role in MM, including KRAS, NRAS, and BRAF.

But many of these telltale mutations were not present in all MM cells. Instead, they were often observed only in a subclonal population.

This suggests targeted therapies may have limitations in patients whose tumors are made up of these subclonal populations, the researchers said.

To explore the therapeutic implications of this research, the team performed follow-up experiments looking specifically at BRAF, a gene for which several inhibitors exist.

Previous studies indicated that roughly 4% of MM patients may have mutations in this gene. And a recent report on a single MM patient treated with drugs targeting BRAF showed promising results.

However, Dr Golub and his colleagues found evidence that treating a tumor harboring subclonal BRAF mutations with one of these agents may, at best, kill a fraction of the cells and, at worst, stimulate another cancer cell subpopulation to grow.

“There’s clearly potential for these drugs in some patients with multiple myeloma, but we show that there are also potential problems for others,” said study author Jens Lohr, MD, PhD, also of Dana-Farber.

“If a patient has a BRAF mutation in less than 100% of his cells, or if he has mutations in KRAS or NRAS at the same time, [it] may influence the response to an inhibitor.”

This suggests subclonal populations could be one of the reasons many patients suffer relapse after treatment, the researchers said.

“Matching the right drug to the right patient may not be as easy as finding a mutation and having a drug that targets it,” Dr Lohr said. “We have to keep this additional parameter of heterogeneity in mind and keep exploring what it means for therapy.”

Subclonal populations in an

MM patient, represented as

different colored cells

Credit: Lauren Solomon

Results of a new study suggest the genetic landscape of multiple myeloma (MM) may be more complex than we thought.

The research revealed “widespread” heterogeneity in samples from more than 200 MM patients.

In some cases, a single patient had multiple mutations in the same pathway. And most of the patients harbored at least 3 detectable subclonal mutations.

The researchers said these findings, published in Cancer Cell, might explain why targeted therapies are not always effective in MM and why some patients relapse after treatment.

“What this new work shows us is that when we treat an individual patient with multiple myeloma, it’s possible that we’re not just looking at one disease, but at many,” said study author Todd Golub, MD, of the Dana-Farber Cancer Institute in Cambridge, Massachusetts.

“In the same person, there could be cancer cells with different genetic make-ups. These findings indicate a need to identify the extent of genetic diversity within a tumor as we move toward precision cancer medicine and genome-based diagnostics.”

Dr Golub and his colleagues studied samples from 203 MM patients and identified frequent mutations in genes known to play an important role in MM, including KRAS, NRAS, and BRAF.

But many of these telltale mutations were not present in all MM cells. Instead, they were often observed only in a subclonal population.

This suggests targeted therapies may have limitations in patients whose tumors are made up of these subclonal populations, the researchers said.

To explore the therapeutic implications of this research, the team performed follow-up experiments looking specifically at BRAF, a gene for which several inhibitors exist.

Previous studies indicated that roughly 4% of MM patients may have mutations in this gene. And a recent report on a single MM patient treated with drugs targeting BRAF showed promising results.

However, Dr Golub and his colleagues found evidence that treating a tumor harboring subclonal BRAF mutations with one of these agents may, at best, kill a fraction of the cells and, at worst, stimulate another cancer cell subpopulation to grow.

“There’s clearly potential for these drugs in some patients with multiple myeloma, but we show that there are also potential problems for others,” said study author Jens Lohr, MD, PhD, also of Dana-Farber.

“If a patient has a BRAF mutation in less than 100% of his cells, or if he has mutations in KRAS or NRAS at the same time, [it] may influence the response to an inhibitor.”

This suggests subclonal populations could be one of the reasons many patients suffer relapse after treatment, the researchers said.

“Matching the right drug to the right patient may not be as easy as finding a mutation and having a drug that targets it,” Dr Lohr said. “We have to keep this additional parameter of heterogeneity in mind and keep exploring what it means for therapy.”

Abstract

• Objective: To review current criteria and rationale for Chlamydia trachomatis screening, testing methods, and treatment of infection.
• Methods: Review of the literature.
• Results: C. trachomatis urogenital infections are an important public health problem. Screening for C. trachomatis in women age 25 and younger and men and women of any age at increased risk allows for the early treatment of disease, avoiding morbidity such as pelvic inflammatory disease, ectopic pregnancy, and chronic pelvic pain, and reducing health care costs.
• Conclusion: Current screening recommendations are not being implemented satisfactorily. Home-based methods of screening are acceptable and may improve universal screening rates.

Abstract

• Objective: To review current criteria and rationale for Chlamydia trachomatis screening, testing methods, and treatment of infection.
• Methods: Review of the literature.
• Results: C. trachomatis urogenital infections are an important public health problem. Screening for C. trachomatis in women age 25 and younger and men and women of any age at increased risk allows for the early treatment of disease, avoiding morbidity such as pelvic inflammatory disease, ectopic pregnancy, and chronic pelvic pain, and reducing health care costs.
• Conclusion: Current screening recommendations are not being implemented satisfactorily. Home-based methods of screening are acceptable and may improve universal screening rates.

Abstract

• Objective: To review current criteria and rationale for Chlamydia trachomatis screening, testing methods, and treatment of infection.
• Methods: Review of the literature.
• Results: C. trachomatis urogenital infections are an important public health problem. Screening for C. trachomatis in women age 25 and younger and men and women of any age at increased risk allows for the early treatment of disease, avoiding morbidity such as pelvic inflammatory disease, ectopic pregnancy, and chronic pelvic pain, and reducing health care costs.
• Conclusion: Current screening recommendations are not being implemented satisfactorily. Home-based methods of screening are acceptable and may improve universal screening rates.

From Children’s Mercy Kansas City, Kansas City, MO.

Abstract

• Objective: To review functional gastrointestinal disorders (FGIDs) in children, with an emphasis on evidence-based diagnostic and treatment approaches.
• Methods: Review of the literature.
• Results: Chronic or recurrent abdominal pain is a common condition in children. No clinical practice guidelines currently exist for pediatric functional abdominal pain broadly or FGIDs more specifically. The Rome classification system includes several discrete diagnostic entities that are diagnosed based on symptom criteria in the absence of red flags. The prevailing biopsychosocial model of pediatric functional abdominal pain suggests that intervening to address biological factors, while providing coping skills and environmental supports to encourage functioning, offers the greatest likelihood of positive treatment outcomes and decreased disability.
• Conclusion: Simultaneously treating all contributors to pain maintenance in FGIDs offers the greatest promise in effectively breaking the pain cycle.

From Children’s Mercy Kansas City, Kansas City, MO.

Abstract

• Objective: To review functional gastrointestinal disorders (FGIDs) in children, with an emphasis on evidence-based diagnostic and treatment approaches.
• Methods: Review of the literature.
• Results: Chronic or recurrent abdominal pain is a common condition in children. No clinical practice guidelines currently exist for pediatric functional abdominal pain broadly or FGIDs more specifically. The Rome classification system includes several discrete diagnostic entities that are diagnosed based on symptom criteria in the absence of red flags. The prevailing biopsychosocial model of pediatric functional abdominal pain suggests that intervening to address biological factors, while providing coping skills and environmental supports to encourage functioning, offers the greatest likelihood of positive treatment outcomes and decreased disability.
• Conclusion: Simultaneously treating all contributors to pain maintenance in FGIDs offers the greatest promise in effectively breaking the pain cycle.

From Children’s Mercy Kansas City, Kansas City, MO.

Abstract

• Objective: To review functional gastrointestinal disorders (FGIDs) in children, with an emphasis on evidence-based diagnostic and treatment approaches.
• Methods: Review of the literature.
• Results: Chronic or recurrent abdominal pain is a common condition in children. No clinical practice guidelines currently exist for pediatric functional abdominal pain broadly or FGIDs more specifically. The Rome classification system includes several discrete diagnostic entities that are diagnosed based on symptom criteria in the absence of red flags. The prevailing biopsychosocial model of pediatric functional abdominal pain suggests that intervening to address biological factors, while providing coping skills and environmental supports to encourage functioning, offers the greatest likelihood of positive treatment outcomes and decreased disability.
• Conclusion: Simultaneously treating all contributors to pain maintenance in FGIDs offers the greatest promise in effectively breaking the pain cycle.

Stem cells in the

artificial bone marrow

Credit: C. Lee-Thedieck

Researchers say they have developed artificial bone marrow analogs that can be used to reproduce hematopoietic stem and progenitor cells (HSPCs).

The team created macroporous hydrogel scaffolds that mimic the stem cell niche of the bone marrow.

When they introduced mesenchymal stem cells (MSCs) from actual bone marrow into the analogs, the MSCs promoted HSPC proliferation.

In fact, the MSCs preserved HSPC stemness more effectively in the analogs than in standard 2-dimensional cell culture systems.

Annamarija Raic, of the Max Planck Institute for Intelligent Systems in Stuttgart, Germany, and her colleagues reported these results in Biomaterials.

The researchers noted that reproducing functional HSPCs in the lab has proven challenging. The cells cannot be cultured in vitro for a feasible period of time without differentiating.

So the team set out to create a culture system that mimics the important physical and biological parameters of the stem cell niche: the 3D architecture, the adhesive extracellular matrix, soluble factors, and the stromal cell compartment.

They used salt leaching technology to produce poly(ethylene glycol) diacrylate hydrogel scaffolds that could soak cells into their pores. To biofunctionalize the scaffolds, the investigators added an RGD peptide carrying an acrylate moiety.

They then introduced 3 different cell types into the scaffolds—the human osteosarcoma cell line CAL72, MSCs from bone marrow, and MSCs from umbilical cord blood—to see which best supported the proliferation of CD34+ HSPCs isolated from cord blood.

Each of the cell types supported HSPC proliferation, but bone marrow MSCs were the most effective. The researchers therefore decided to use bone marrow MSCs when they compared their 3D scaffolds to a 2D culture system.

The bone marrow MSCs had a beneficial effect on HSPC proliferation in the 2D cell cultures. Over 4 days, HSPCs divided 1 to 2 times more often when they were cultured with bone marrow MSCs than without the cells.

In the 3D scaffolds, HSPC proliferation was comparable or slightly lower than that observed in the 2D cultures. However, the scaffolds had a higher percentage of CD34+ HSPCs after 4 days.

The investigators therefore concluded that their hydrogel scaffolds meet the basic requirements for creating artificial stem cell niches.

Stem cells in the

artificial bone marrow

Credit: C. Lee-Thedieck

Researchers say they have developed artificial bone marrow analogs that can be used to reproduce hematopoietic stem and progenitor cells (HSPCs).

The team created macroporous hydrogel scaffolds that mimic the stem cell niche of the bone marrow.

When they introduced mesenchymal stem cells (MSCs) from actual bone marrow into the analogs, the MSCs promoted HSPC proliferation.

In fact, the MSCs preserved HSPC stemness more effectively in the analogs than in standard 2-dimensional cell culture systems.

Annamarija Raic, of the Max Planck Institute for Intelligent Systems in Stuttgart, Germany, and her colleagues reported these results in Biomaterials.

The researchers noted that reproducing functional HSPCs in the lab has proven challenging. The cells cannot be cultured in vitro for a feasible period of time without differentiating.

So the team set out to create a culture system that mimics the important physical and biological parameters of the stem cell niche: the 3D architecture, the adhesive extracellular matrix, soluble factors, and the stromal cell compartment.

They used salt leaching technology to produce poly(ethylene glycol) diacrylate hydrogel scaffolds that could soak cells into their pores. To biofunctionalize the scaffolds, the investigators added an RGD peptide carrying an acrylate moiety.

They then introduced 3 different cell types into the scaffolds—the human osteosarcoma cell line CAL72, MSCs from bone marrow, and MSCs from umbilical cord blood—to see which best supported the proliferation of CD34+ HSPCs isolated from cord blood.

Each of the cell types supported HSPC proliferation, but bone marrow MSCs were the most effective. The researchers therefore decided to use bone marrow MSCs when they compared their 3D scaffolds to a 2D culture system.

The bone marrow MSCs had a beneficial effect on HSPC proliferation in the 2D cell cultures. Over 4 days, HSPCs divided 1 to 2 times more often when they were cultured with bone marrow MSCs than without the cells.

In the 3D scaffolds, HSPC proliferation was comparable or slightly lower than that observed in the 2D cultures. However, the scaffolds had a higher percentage of CD34+ HSPCs after 4 days.

The investigators therefore concluded that their hydrogel scaffolds meet the basic requirements for creating artificial stem cell niches.

Stem cells in the

artificial bone marrow

Credit: C. Lee-Thedieck

Researchers say they have developed artificial bone marrow analogs that can be used to reproduce hematopoietic stem and progenitor cells (HSPCs).

The team created macroporous hydrogel scaffolds that mimic the stem cell niche of the bone marrow.

When they introduced mesenchymal stem cells (MSCs) from actual bone marrow into the analogs, the MSCs promoted HSPC proliferation.

In fact, the MSCs preserved HSPC stemness more effectively in the analogs than in standard 2-dimensional cell culture systems.

Annamarija Raic, of the Max Planck Institute for Intelligent Systems in Stuttgart, Germany, and her colleagues reported these results in Biomaterials.

The researchers noted that reproducing functional HSPCs in the lab has proven challenging. The cells cannot be cultured in vitro for a feasible period of time without differentiating.

So the team set out to create a culture system that mimics the important physical and biological parameters of the stem cell niche: the 3D architecture, the adhesive extracellular matrix, soluble factors, and the stromal cell compartment.

They used salt leaching technology to produce poly(ethylene glycol) diacrylate hydrogel scaffolds that could soak cells into their pores. To biofunctionalize the scaffolds, the investigators added an RGD peptide carrying an acrylate moiety.

They then introduced 3 different cell types into the scaffolds—the human osteosarcoma cell line CAL72, MSCs from bone marrow, and MSCs from umbilical cord blood—to see which best supported the proliferation of CD34+ HSPCs isolated from cord blood.

Each of the cell types supported HSPC proliferation, but bone marrow MSCs were the most effective. The researchers therefore decided to use bone marrow MSCs when they compared their 3D scaffolds to a 2D culture system.

The bone marrow MSCs had a beneficial effect on HSPC proliferation in the 2D cell cultures. Over 4 days, HSPCs divided 1 to 2 times more often when they were cultured with bone marrow MSCs than without the cells.

In the 3D scaffolds, HSPC proliferation was comparable or slightly lower than that observed in the 2D cultures. However, the scaffolds had a higher percentage of CD34+ HSPCs after 4 days.

The investigators therefore concluded that their hydrogel scaffolds meet the basic requirements for creating artificial stem cell niches.

NK cell in action

Credit: Bjorn Onfelt/Dan Davis

The parasites that cause malaria are adapted to the hosts they infect, so studying the disease in mice doesn’t necessarily reveal information that translates to human disease.

But scientists believe they may have overcome this limitation. They’ve developed a strain of mice that mimics many features of the human immune system and can be infected with Plasmodium falciparum.

Using this strain, the researchers discovered that natural killer (NK) cells preferentially interact with and kill infected red blood cells (RBCs) in a contact-dependent manner.

The group recounted this discovery in PNAS.

“Human malaria studies have been hampered by a lack of animal models,” said study author Jianzhu Chen, PhD, of the Singapore-MIT Alliance for Research and Technology in Singapore.

“This [research] paves the way to start dissecting how the host human immune system interacts with the pathogen.”

Scientists studying malaria in mice previously generated mice with human RBCs. But these mice have compromised immune systems, so they can’t be used to study the immune response to malaria infection.

Over the past several years, Dr Chen and his colleagues have developed strains of mice that have the human cells necessary for a comprehensive immune response.

To generate these cells, the researchers deliver human hematopoietic stem cells, along with cytokines that help them mature into B and T cells, NK cells, and macrophages. These mice have already proven useful to study other diseases, such as dengue fever.

To adapt the mice for the study of malaria, the scientists injected them with human RBCs every day for a week, at which point 25% of their RBCs were human. And this was enough for the malaria parasite to cause an infection.

The researchers investigated the role of NK cells and macrophages during the first 2 days of malaria infection. And they found that eliminating macrophages had very little impact on the immune response during those early stages.

However, in mice lacking NK cells, parasite levels went up 7-fold, suggesting that NK cells are critical to controlling infection early on.

To further investigate the role of NK cells, the scientists placed human NK cells in a sample of infected and uninfected RBCs. The NK cells randomly interacted with both types of cells, but they latched onto infected cells much longer, eventually killing them.

The researchers also identified a cell adhesion protein called LFA-1 that helps NK cells bind to RBCs. They are now studying this process in more detail and trying to determine what other molecules, including those produced by the malaria parasite, might be involved.

Dr Chen and his colleagues also hope to use these mice to study experimental malaria vaccines or drugs. And in another future study, they plan to inject the mice with RBCs from patients with sickle cell anemia to investigate how the sickle-shaped cells help people survive malaria infection.

NK cell in action

Credit: Bjorn Onfelt/Dan Davis

The parasites that cause malaria are adapted to the hosts they infect, so studying the disease in mice doesn’t necessarily reveal information that translates to human disease.

But scientists believe they may have overcome this limitation. They’ve developed a strain of mice that mimics many features of the human immune system and can be infected with Plasmodium falciparum.

Using this strain, the researchers discovered that natural killer (NK) cells preferentially interact with and kill infected red blood cells (RBCs) in a contact-dependent manner.

The group recounted this discovery in PNAS.

“Human malaria studies have been hampered by a lack of animal models,” said study author Jianzhu Chen, PhD, of the Singapore-MIT Alliance for Research and Technology in Singapore.

“This [research] paves the way to start dissecting how the host human immune system interacts with the pathogen.”

Scientists studying malaria in mice previously generated mice with human RBCs. But these mice have compromised immune systems, so they can’t be used to study the immune response to malaria infection.

Over the past several years, Dr Chen and his colleagues have developed strains of mice that have the human cells necessary for a comprehensive immune response.

To generate these cells, the researchers deliver human hematopoietic stem cells, along with cytokines that help them mature into B and T cells, NK cells, and macrophages. These mice have already proven useful to study other diseases, such as dengue fever.

To adapt the mice for the study of malaria, the scientists injected them with human RBCs every day for a week, at which point 25% of their RBCs were human. And this was enough for the malaria parasite to cause an infection.

The researchers investigated the role of NK cells and macrophages during the first 2 days of malaria infection. And they found that eliminating macrophages had very little impact on the immune response during those early stages.

However, in mice lacking NK cells, parasite levels went up 7-fold, suggesting that NK cells are critical to controlling infection early on.

To further investigate the role of NK cells, the scientists placed human NK cells in a sample of infected and uninfected RBCs. The NK cells randomly interacted with both types of cells, but they latched onto infected cells much longer, eventually killing them.

The researchers also identified a cell adhesion protein called LFA-1 that helps NK cells bind to RBCs. They are now studying this process in more detail and trying to determine what other molecules, including those produced by the malaria parasite, might be involved.

Dr Chen and his colleagues also hope to use these mice to study experimental malaria vaccines or drugs. And in another future study, they plan to inject the mice with RBCs from patients with sickle cell anemia to investigate how the sickle-shaped cells help people survive malaria infection.

NK cell in action

Credit: Bjorn Onfelt/Dan Davis

The parasites that cause malaria are adapted to the hosts they infect, so studying the disease in mice doesn’t necessarily reveal information that translates to human disease.

But scientists believe they may have overcome this limitation. They’ve developed a strain of mice that mimics many features of the human immune system and can be infected with Plasmodium falciparum.

Using this strain, the researchers discovered that natural killer (NK) cells preferentially interact with and kill infected red blood cells (RBCs) in a contact-dependent manner.

The group recounted this discovery in PNAS.

“Human malaria studies have been hampered by a lack of animal models,” said study author Jianzhu Chen, PhD, of the Singapore-MIT Alliance for Research and Technology in Singapore.

“This [research] paves the way to start dissecting how the host human immune system interacts with the pathogen.”

Scientists studying malaria in mice previously generated mice with human RBCs. But these mice have compromised immune systems, so they can’t be used to study the immune response to malaria infection.

Over the past several years, Dr Chen and his colleagues have developed strains of mice that have the human cells necessary for a comprehensive immune response.

To generate these cells, the researchers deliver human hematopoietic stem cells, along with cytokines that help them mature into B and T cells, NK cells, and macrophages. These mice have already proven useful to study other diseases, such as dengue fever.

To adapt the mice for the study of malaria, the scientists injected them with human RBCs every day for a week, at which point 25% of their RBCs were human. And this was enough for the malaria parasite to cause an infection.

The researchers investigated the role of NK cells and macrophages during the first 2 days of malaria infection. And they found that eliminating macrophages had very little impact on the immune response during those early stages.

However, in mice lacking NK cells, parasite levels went up 7-fold, suggesting that NK cells are critical to controlling infection early on.

To further investigate the role of NK cells, the scientists placed human NK cells in a sample of infected and uninfected RBCs. The NK cells randomly interacted with both types of cells, but they latched onto infected cells much longer, eventually killing them.

The researchers also identified a cell adhesion protein called LFA-1 that helps NK cells bind to RBCs. They are now studying this process in more detail and trying to determine what other molecules, including those produced by the malaria parasite, might be involved.

Dr Chen and his colleagues also hope to use these mice to study experimental malaria vaccines or drugs. And in another future study, they plan to inject the mice with RBCs from patients with sickle cell anemia to investigate how the sickle-shaped cells help people survive malaria infection.