Scientists generate first human stomach tissue in lab with stem cells

 

October 29, 2014

Cincinnati Children's Hospital Medical Center

Scientists used pluripotent stem cells to generate functional, three-dimensional human stomach tissue in a laboratory -- creating an unprecedented tool for researching the development and diseases of an organ central to several public health crises, ranging from cancer to diabetes. Scientists used human pluripotent stem cells -- which can become any cell type in the body -- to grow a miniature version of the stomach.

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Jim Wells, PhD, Divisions of Developmental Biology and Endocrinology at Cincinnati Children’s, explains how the first-time molecular generation of 3D human gastric organoids (hGOs) presents new opportunities for drug discovery, modeling early stages of stomach cancer, studying the underpinnings of obesity related diabetes, and potential tissue regeneration for therapy.

Scientists used pluripotent stem cells to generate functional, three-dimensional human stomach tissue in a laboratory -- creating an unprecedented tool for researching the development and diseases of an organ central to several public health crises, ranging from cancer to diabetes.

Scientists at Cincinnati Children's Hospital Medical Center report Oct. 29 in Nature they used human pluripotent stem cells -- which can become any cell type in the body -- to grow a miniature version of the stomach. In collaboration with researchers at the University of Cincinnati College of Medicine, they used laboratory generated mini-stomachs (called gastric organoids) to study infection by H. pylori bacteria, a major cause of peptic ulcer disease and stomach cancer.

This first-time molecular generation of 3D human gastric organoids (hGOs) presents new opportunities for drug discovery, modeling early stages of stomach cancer and studying some of the underpinnings of obesity related diabetes, according to Jim Wells, PhD, principal investigator and a scientist in the divisions of Developmental Biology and Endocrinology at Cincinnati Children's.

It also is the first time researchers have produced 3D human embryonic foregut -- a promising starting point for generating other foregut organ tissues like the lungs and pancreas, he said.

"Until this study, no one had generated gastric cells from human pluripotent stem cells (hPSCs)," Wells said. "In addition, we discovered how to promote formation of three-dimensional gastric tissue with complex architecture and cellular composition."

This is important because differences between species in the embryonic development and architecture of the adult stomach make mouse models less than optimal for studying human stomach development and disease, Wells added.

Researchers can use human gastric organoids as a new discovery tool to help unlock other secrets of the stomach, such as identifying biochemical processes in the gut that allow gastric-bypass patients to become diabetes-free soon after surgery before losing significant weight. Obesity fueled diabetes and metabolic syndrome are an exploding public health epidemic. Until now, a major challenge to addressing these and other medical conditions involving the stomach has been a relative lack of reliable laboratory modeling systems to accurately simulate human biology, Wells explained.

The key to growing human gastric organoids was to identify the steps involved in normal stomach formation during embryonic development. By manipulating these normal processes in a petri dish, the scientists were able to coax pluripotent stem cells toward becoming stomach. Over the course of a month, these steps resulted in the formation of 3D human gastric organoids that were about 3mm (1/10th of an inch) in diameter. Wells and his colleagues also used this approach to identify what drives normal stomach formation in humans with the goal of understanding what goes wrong when the stomach does not form correctly.

Along with study first author Kyle McCracken, an MD/PhD graduate student working in Wells' laboratory, and Yana Zavros, PhD, a researcher at UC's Department of Molecular and Cellular Physiology, the authors report they were impressed by how rapidly H. pylori bacteria infected stomach epithelial tissues.

Within 24 hours, the bacteria had triggered biochemical changes to the organ, according to McCracken. The human gastric organoids faithfully mimicked the early stages of gastric disease caused by the bacteria, including the activation of a cancer gene called c-Met and the rapid spread of infection in epithelial tissues.

Another significant part of the team's challenge has been the relative lack of previous research literature on how the human stomach develops, the authors said. Wells said the scientists had to use a combination of published work, as well as studies from his own lab, to answer a number of basic developmental questions about how the stomach forms. Over the course of two years, this approach of experimenting with different factors to drive the formation of the stomach eventually resulted in the formation of 3D human gastric tissues in the petri dish.

Wells emphasized importance of basic research for the eventual success of this project, adding, "This milestone would not have been possible if it hadn't been for previous studies from many other basic researchers on understanding embryonic organ development."

Video: http://www.youtube.com/watch?v=KwSe8xBAKpA

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Story Source:

The above story is based on materials provided by Cincinnati Children's Hospital Medical Center. Note: Materials may be edited for content and length.

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Journal Reference:

1. Kyle W. McCracken, Emily M. Catá, Calyn M. Crawford, Katie L. Sinagoga, Michael Schumacher, Briana E. Rockich, Yu-Hwai Tsai, Christopher N. Mayhew, Jason R. Spence, Yana Zavros, James M. Wells. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature, 2014; DOI: 10.1038/nature13863

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Growing a blood vessel in a week

 

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The technology for creating new tissues from stem cells has taken a giant leap forward. Two tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days.

The technology for creating new tissues from stem cells has taken a giant leap forward. Three tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days. This is shown in a new study from Sahlgrenska Acadedmy and Sahlgrenska University Hospital published in EBioMedicine.

Just three years ago, a patient at Sahlgrenska University Hospital received a blood vessel transplant grown from her own stem cells.

Suchitra Sumitran-Holgersson, Professor of Transplantation Biology at Sahlgrenska Academy, and Michael Olausson, Surgeon/Medical Director of the Transplant Center and Professor at Sahlgrenska Academy, came up with the idea, planned and carried out the procedure.

Missing a vein

Professors Sumitran-Holgersson and Olausson have published a new study in EBioMedicine based on two other transplants that were performed in 2012 at Sahlgrenska University Hospital. The patients, two young children, had the same condition as in the first case -- they were missing the vein that goes from the gastrointestinal tract to the liver.

"Once again we used the stem cells of the patients to grow a new blood vessel that would permit the two organs to collaborate properly," Professor Olausson says.

This time, however, Professor Sumitran-Holgersson, found a way to extract stem cells that did not necessitate taking them from the bone marrow.

"Drilling in the bone marrow is very painful," she says. "It occurred to me that there must be a way to obtain the cells from the blood instead."

The fact that the patients were so young fueled her passion to look for a new approach. The method involved taking 25 milliliter (approximately 2 tablespoons) of blood, the minimum quantity needed to obtain enough stem cells.

Blood willingly cooperates

Professor Sumitran-Holgersson's idea turned out to surpass her wildest expectations -- the extraction procedure worked perfectly the very first time.

"Not only that, but the blood itself accelerated growth of the new vein," Professor Sumitran-Holgersson says. "The entire process took only a week, as opposed to a month in the first case. The blood contains substances that naturally promote growth."

More groups of patients can benefit

Professors Olausson and Sumitran-Holgersson have treated three patients so far. Two of the three patients are still doing well and have veins that are functioning as they should. In the third case the child is under medical surveillance and the outcome is more uncertain.

They researchers have now reached the point that they can avoid taking painful blood marrow samples and complete the entire process in the matter of a week.

"We believe that this technological progress can lead to dissemination of the method for the benefit of additional groups of patients, such as those with varicose veins or myocardial infarction, who need new blood vessels," Professor Holgersson says. "Our dream is to be able to grow complete organs as a way of overcoming the current shortage from donors."

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Story Source:

The above story is based on materials provided by University of Gothenburg. The original article was written by Krister Svahn. Note: Materials may be edited for content and length.

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Journal Reference:

1. Michael Olausson, Vijay Kumar Kuna, Galyna Travnikova, Henrik Bäckdahl, Pradeep B. Patil, Robert Saalman, Helena Borg, Anders Jeppsson, Suchitra Sumitran-Holgersson. In vivo application of tissue-engineered veins using autologous peripheral whole blood: A proof of concept study. EBioMedicine, 2014; DOI: 10.1016/j.ebiom.2014.09.001

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Combining antibodies, iron nanoparticles and magnets steers stem cells to injured organs

 

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Researchers at the Cedars-Sinai Heart Institute infused antibody-studded iron nanoparticles into the bloodstream to treat heart attack damage. The combined nanoparticle enabled precise localization of the body's own stem cells to the injured heart muscle.

The study, which focused on laboratory rats, was published today in the online peer reviewed journal Nature Communications. The study addresses a central challenge in stem cell therapeutics: how to achieve targeted interactions between stem cells and injured cells.

Although stem cells can be a potent weapon in the fight against certain diseases, simply infusing a patient with stem cells is no guarantee the stem cells will be able to travel to the injured area and work collaboratively with the cells already there.

"Infusing stem cells into arteries in order to regenerate injured heart muscle can be inefficient," said Eduardo Marbán, MD, PhD, director of the Cedars-Sinai Heart Institute, who led the research team. "Because the heart is continuously pumping, the stem cells can be pushed out of the heart chamber before they even get a chance to begin to heal the injury."

In an attempt to target healing stem cells to the site of the injury, researchers coated iron nanoparticles with two kinds of antibodies, proteins that recognize and bind specifically to stem cells and to injured cells in the body. After the nanoparticles were infused into the bloodstream, they successfully tracked to the injured area and initiated healing.

"The result is a kind of molecular matchmaking," Marbán said. "Through magnetic resonance imaging, we were able to see the iron-tagged cells traveling to the site of injury where the healing could begin. Furthermore, targeting was enhanced even further by placing a magnet above the injured heart."

The Cedars-Sinai Heart Institute has been at the forefront of developing investigational stem cell treatments for heart attack patients. In 2009, Marbán and his team completed the world's first procedure in which a patient's own heart tissue was used to grow specialized heart stem cells. The specialized cells were then injected back into the patient's heart in an effort to repair and regrow healthy muscle in a heart that had been injured by a heart attack. Results, published in The Lancet in 2012, showed that one year after receiving the stem cell treatment, heart attack patients demonstrated a significant reduction in the size of the scar left on the heart muscle.

Earlier this year, Heart Institute researchers began a new study, called ALLSTAR, in which heart attack patients are being infused with allogeneic stem cells, which are derived from donor-quality hearts.

The process to grow cardiac-derived stem cells was developed by Dr. Marbán when he was on the faculty of Johns Hopkins University. Johns Hopkins has filed for a patent on that intellectual property and has licensed it to Capricor, a company in which Cedars-Sinai and Dr. Marbán have a financial interest. Capricor is providing funds for the ALLSTAR clinical trial at Cedars-Sinai.

Recently, the Heart Institute opened the nation's first Regenerative Medicine Clinic, designed to match heart and vascular disease patients with appropriate stem cell clinical trials being conducted at Cedars-Sinai and other institutions.

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Story Source:

The above story is based on materials provided by Cedars-Sinai Medical Center. Note: Materials may be edited for content and length.

Stem cells hold keys to body's plan

 

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Four-cell embryo (stock illustration). Researchers have discovered landmarks within pluripotent stem cells that guide how they develop to serve different purposes within the body. This breakthrough offers promise that scientists eventually will be able to direct stem cells in ways that prevent disease or repair damage from injury or illness. Pluripotent stem cells are so named because they can evolve into any of the cell types that exist within the body.

Case Western Reserve researchers have discovered landmarks within pluripotent stem cells that guide how they develop to serve different purposes within the body. This breakthrough offers promise that scientists eventually will be able to direct stem cells in ways that prevent disease or repair damage from injury or illness. The study and its results appear in the June 5 edition of the journal Cell Stem Cell.

Pluripotent stem cells are so named because they can evolve into any of the cell types that exist within the body. Their immense potential captured the attention of two accomplished faculty with complementary areas of expertise.

"We had a unique opportunity to bring together two interdisciplinary groups," said co-senior author Paul Tesar, PhD, Assistant Professor of Genetics and Genome Sciences at CWRU School of Medicine and the Dr. Donald and Ruth Weber Goodman Professor.

"We have exploited the Tesar lab's expertise in stem cell biology and my lab's expertise in genomics to uncover a new class of genetic switches, which we call seed enhancers," said co-senior author Peter Scacheri, PhD, Associate Professor of Genetics and Genome Sciences at CWRU School of Medicine. "Seed enhancers give us new clues to how cells morph from one cell type to another during development."

The breakthrough came from studying two closely related stem cell types that represent the earliest phases of development -- embryonic stem cells and epiblast stem cells, first described in research by Tesar in 2007. "These two stem cell types give us unprecedented access to the earliest stages of mammalian development," said Daniel Factor, graduate student in the Tesar lab and co-first author of the study.

Olivia Corradin, graduate student in the Scacheri lab and co-first author, agrees. "Stem cells are touted for their promise to make replacement tissues for regenerative medicine," she said. "But first, we have to understand precisely how these cells function to create diverse tissues."

Enhancers are sections of DNA that control the expression of nearby genes. By comparing these two closely related types of pluripotent stem cells (embryonic and epiblast), Corradin and Factor identified a new class of enhancers, which they refer to as seed enhancers. Unlike most enhancers, which are only active in specific times or places in the body, seed enhancers play roles from before birth to adulthood.

They are present, but dormant, in the early mouse embryonic stem cell population. In the more developed mouse epiblast stem cell population, they become the primary enhancers of their associated genes. As the cells mature into functional adult tissues, the seed enhancers grow into super enhancers. Super enhancers are large regions that contain many enhancers and control the most important genes in each cell type.

"These seed enhancers have wide-ranging potential to impact the understanding of development and disease," said Stanton Gerson, MD, Asa & Patricia Shiverick and Jane Shiverick (Tripp) Professor of Hematological Oncology and Director of the National Center for Regenerative Medicine at Case Western Reserve University. "In the stem cell field, this understanding should rapidly enhance the ability to generate clinically useful cell types for stem cell-based regenerative medicine."

"Our next step is to understand if mis-regulation of these seed enhancers might play a role in human diseases," Tesar said. "The genes controlled by seed enhancers are powerful ones, and it's possible that aberrations could contribute to things like heart disease or neurodegenerative disorders."

Scacheri added, "It is also clear that cancer can be driven by changes in enhancers, and we are interested in understanding the role of seed enhancers in cancer onset and progression."

Results in Phase I Trial Targeting Cancer Stem Cells

 

May 31, 2014

University of Colorado Cancer Center

Results of a Phase I trial of OMP-54F28 (FZD8-Fc), an investigational drug candidate targeting cancer stem cells (CSCs) have been released. The drug was generally well tolerated, and several of the 26 patients with advanced solid tumors experienced stable disease for greater than six months. Three trials are now open in combinations with standard therapy for pancreatic, ovarian and liver cancers.

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At the 50th Annual Meeting of the American Society for Clinical Oncology (ASCO), University of Colorado Cancer Center researchers reported results of a Phase I trial of OMP-54F28 (FZD8-Fc), an investigational drug candidate discovered by OncoMed Pharmaceuticals targeting cancer stem cells (CSCs). The drug was generally well tolerated, and several of the 26 patients with advanced solid tumors experienced stable disease for greater than six months. Three trials are now open for OMP-54F28 (FZD8-Fc) in combinations with standard therapy for pancreatic, ovarian and liver cancers, being offered at the CU Cancer Center and elsewhere.

"These are optimistic results for one of the first targeted therapies for cancer stem cells," says Antonio Jimeno, MD, PhD, investigator at the CU Cancer Center, director of the university's Cancer Stem Cell-Directed Clinical Trials Program, and principal investigator of the clinical trial at the CU Cancer Center site. "And it is great to work with such a science-focused sponsor, whose vision aligns with ours: bringing to the clinic cutting-edge drugs and ideas that are focused on targeting CSCs. In the context of the collaboration between the Gates Center for Stem Cell Biology and the CU Cancer Center this was the second clinical trial we offered to our patients with the specific intent to eliminate the CSCs in their tumors."

OMP-54F28 (FZD8-Fc) is an antagonist of the Wnt pathway, a key CSC signaling pathway that regulates the fate of these cells. The Wnt pathway is known to be inappropriately activated in many major tumor types, including colon, breast, liver, lung and pancreatic cancers, and is critical for the function of CSCs. Because of this extensive validation, in the Jimeno lab and elsewhere, the Wnt pathway has been a major focus of anti-cancer drug discovery efforts. OMP-54F28 (FZD8-Fc) and a sister compound also developed by OncoMed, vantictumab (OMP-18R5), are two of the first therapeutic agents targeting this key pathway to enter clinical testing. In multiple preclinical models, OMP-54F28 (FZD8-Fc) has shown its effectiveness in reducing CSC populations, leading to associated anti-tumor activity, either as a single agent or when combined with chemotherapy.

"The ongoing line of work with this drug is an excellent example of the bench getting even closer to the bedside -- our lab work with the drug in patient-derived xenograft models of disease makes possible the clinical trials taking place at the University of Colorado Hospital next door," Jimeno says.

The Phase I clinical trial of OMP-54F28 (FZD8-Fc) is an open-label dose escalation study in patients with advanced solid tumors for which there was no remaining standard curative therapy. Patients are assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and initial signals of efficacy. The trial is conducted at Pinnacle Oncology Hematology in Scottsdale, Arizona, the University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, and the CU Cancer Center under the direction of Principal Investigators Dr. Michael S. Gordon, Dr. David Smith and Dr. Antonio Jimeno, respectively.

The most common adverse events, mild to moderate and manageable, included dysgeusia (altered taste), fatigue, muscle spasms, decreased appetite, alopecia and nausea. One related Grade 3 or greater adverse event of Grade 3 increased blood phosphorus was reported. One moderate sacral insufficiency fracture occurred in one patient at the highest tested dose of 20 mg/kg every three weeks after 6 cycles.

"The drug is now being developed in combination with standard of care in three Phase 1b clinical trials, with the CU Cancer Center being one of the active sites," Jimeno says. "In pancreatic, ovarian and liver cancers, we hope that by adding anti-cancer stem cell drugs to standard of care, we can control proliferating cells within the tumor that could otherwise help the tumor regenerate in the face of existing chemotherapies."

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Story Source:

The above story is based on materials provided by University of Colorado Cancer Center. Note: Materials may be edited for content and length.

First test of pluripotent stem cell therapy in monkeys is successful

 

May 15, 2014

 

For the first time in an animal that is more closely related to humans, researchers have demonstrated that it is possible to make new bone from stem-cell-like induced pluripotent stem cells (iPSCs) made from an individual animal's own skin cells. The study in monkeys also shows that there is some risk that those iPSCs could seed tumors, but that unfortunate outcome appears to be less likely than studies in immune-compromised mice would suggest.

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Rhesus macaque (stock image). "We have been able to design an animal model for testing of pluripotent stem cell therapies using the rhesus macaque, a small monkey that is readily available and has been validated as being closely related physiologically to humans," said Cynthia Dunbar of the National Heart, Lung, and Blood Institute.

Researchers have shown for the first time in an animal that is more closely related to humans that it is possible to make new bone from stem-cell-like induced pluripotent stem cells (iPSCs) made from an individual animal's own skin cells. The study in monkeys reported in the Cell Press journal Cell Reports on May 15th also shows that there is some risk that those iPSCs could seed tumors, but that unfortunate outcome appears to be less likely than studies in immune-compromised mice would suggest.

"We have been able to design an animal model for testing of pluripotent stem cell therapies using the rhesus macaque, a small monkey that is readily available and has been validated as being closely related physiologically to humans," said Cynthia Dunbar of the National Heart, Lung, and Blood Institute. "We have used this model to demonstrate that tumor formation of a type called a 'teratoma' from undifferentiated autologous iPSCs does occur; however, tumor formation is very slow and requires large numbers of iPSCs given under very hospitable conditions. We have also shown that new bone can be produced from autologous iPSCs, as a model for their possible clinical application."

Autologous refers to the fact that the iPSCs capable of producing any tissue type—in this case bone—were derived from the very individual that later received them. That means that use of these cells in tissue repair would not require long-term or possibly toxic immune suppression drugs to prevent rejection.

The researchers first used a standard recipe to reprogram skin cells taken from rhesus macaques. They then coaxed those cells to form first pluripotent stem cells and then cells that have the potential to act more specifically as bone progenitors. Those progenitor cells were then seeded onto ceramic scaffolds that are already in use by reconstructive surgeons attempting to fill in or rebuild bone. And, it worked; the monkeys grew new bone.

Importantly, the researchers report that no teratoma structures developed in monkeys that had received the bone "stem cells." In other experiments, undifferentiated iPSCs did form teratomas in a dose-dependent manner.

The researchers say that therapies based on this approach could be particularly beneficial for people with large congenital bone defects or other traumatic injuries. Although bone replacement is an unlikely "first in human" use for stem cell therapies given that the condition it treats is not life threatening, the findings in a primate are an essential step on the path toward regenerative clinical medicine.

"A large animal preclinical model for the development of pluripotent or other high-risk/high-reward generative cell therapies is absolutely required to address issues of tissue integration or homing, risk of tumor formation, and immunogenicity," Dunbar said. "The testing of human-derived cells in vitro or in profoundly immunodeficient mice simply cannot model these crucial preclinical safety and efficiency issues."

The NIH team is now working with collaborators on differentiation of the macaque iPSCs into liver, heart, and white blood cells for eventual clinical trials in hepatitis C, heart failure, and chronic granulomatous disease, respectively.

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Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.

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Journal Reference:

1. So Gun Hong, Thomas Winkler, Chuanfeng Wu, Vicky Guo, Stefania Pittaluga, Alina Nicolae, Robert E. Donahue, Mark E. Metzger, Sandra D. Price, Naoya Uchida, Sergei A. Kuznetsov, Tina Kilts, Li Li, Pamela G. Robey, Cynthia E. Dunbar. Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model. Cell Reports, 2014; DOI: 10.1016/j.celrep.2014.04.019

Herpes-loaded stem cells used to kill brain tumors

 

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Harvard Stem Cell Institute (HSCI) scientists at Massachusetts General Hospital have a potential solution for how to more effectively kill tumor cells using cancer-killing viruses. The investigators report that trapping virus-loaded stem cells in a gel and applying them to tumors significantly improved survival in mice with glioblastoma multiforme, the most common brain tumor in human adults and also the most difficult to treat.

The work, led by Khalid Shah, MS, PhD, an HSCI Principal Faculty member, is published in the Journal of the National Cancer Institute. Shah heads the Molecular Neurotherapy and Imaging Laboratory at Massachusetts General Hospital.

Cancer-killing or oncolytic viruses have been used in numerous phase 1 and 2 clinical trials for brain tumors but with limited success. In preclinical studies, oncolytic herpes simplex viruses seemed especially promising, as they naturally infect dividing brain cells. However, the therapy hasn't translated as well for human patients. The problem previous researchers couldn't overcome was how to keep the herpes viruses at the tumor site long enough to work.

Shah and his team turned to mesenchymal stem cells (MSCs) -- a type of stem cell that gives rise to bone marrow tissue -- which have been very attractive drug delivery vehicles because they trigger a minimal immune response and can be utilized to carry oncolytic viruses. Shah and his team loaded the herpes virus into human MSCs and injected the cells into glioblastoma tumors developed in mice. Using multiple imaging markers, it was possible to watch the virus as it passed from the stem cells to the first layer of brain tumor cells and subsequently into all of the tumor cells.

"So, how do you translate this into the clinic?" asked Shah, who also is an Associate Professor at Harvard Medical School.

"We know that 70-75 percent of glioblastoma patients undergo surgery for tumor debulking, and we have previously shown that MSCs encapsulated in biocompatible gels can be used as therapeutic agents in a mouse model that mimics this debulking," he continued. "So, we loaded MSCs with oncolytic herpes virus and encapsulated these cells in biocompatible gels and applied the gels directly onto the adjacent tissue after debulking. We then compared the efficacy of virus-loaded, encapsulated MSCs versus direct injection of the virus into the cavity of the debulked tumors."

Using imaging proteins to watch in real time how the virus combated the cancer, Shah's team noticed that the gel kept the stem cells alive longer, which allowed the virus to replicate and kill any residual cancer cells that were not cut out during the debulking surgery. This translated into a higher survival rate for mice that received the gel-encapsulated stem cells.

"They survived because the virus doesn't get washed out by the cerebrospinal fluid that fills the cavity," Shah said. "Previous studies that have injected the virus directly into the resection cavity did not follow the fate of the virus in the cavity. However, our imaging and side-by-side comparison studies showed that the naked virus rarely infects the residual tumor cells. This could give us insight into why the results from clinical trials with oncolytic viruses alone were modest."

The study also addressed another weakness of cancer-killing viruses, which is that not all brain tumors are susceptible to the therapy. The researchers' solution was to engineer oncolytic herpes viruses to express an additional tumor-killing agent, called TRAIL. Again, using mouse models of glioblastoma -- this time created from brain tumor cells that were resistant to the herpes virus -- the therapy led to increased animal survival.

"Our approach can overcome problems associated with current clinical procedures," Shah said. "The work will have direct implications for designing clinical trials using oncolytic viruses, not only for brain tumors, but for other solid tumors."

Further preclinical work will be needed to use the herpes-loaded stem cells for breast, lung and skin cancer tumors that metastasize to the brain. Shah predicts the approach will enter clinical trials within the next two to three years.

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Story Source:

The above story is based on materials provided by Harvard University. Note: Materials may be edited for content and length.

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Journal Reference:

1. Matthias Duebgen, Jordi Martinez-Quintanilla, Kaoru Tamura, Shawn Hingtgen, Navid Redjal, Hiroaki Wakimoto And Khalid Shah. Stem Cells Loaded With Multimechanistic Oncolytic Herpes Simplex Virus Variants for Brain Tumor Therapy. Journal of the National Cancer Institute, May 2014 DOI: 10.1093/jnci/dju090