HIV

Investing in stem cell and gene therapy treatments for HIV

/ Esteban Cortez / 1 Comment

A recent article in Nature shared the news about a 53-year-old man in Germany who was declared free of HIV after receiving virus-resistant cells. 

The man—referred to as the “Düsseldorf patient”—was diagnosed with acute myeloid leukemia and underwent a stem cell transplant in 2013 that replaced his bone marrow cells with HIV-resistant stem cells from a donor.  

In the five years following the procedure, virologist Björn-Erik Jensen and his team at Düsseldorf University Hospital in Germany continued to monitor the patient. They continued to find immune cells that reacted to HIV in his body, which suggested that his body was not clear of the virus. 

In 2018, the patient stopped taking antiretroviral therapy (ART), a treatment for HIV that reduces a person’s viral load to an undetectable level. His body has remained HIV-free since then, indicating that the stem cell transplant worked.  

Similar stem cell treatments have been used to treat others living with HIV, including a patient in 2007 and another patient in 2019. 

The article in Nature states that the procedure is unlikely to be used widely in its current form due to the associated risks, including the chance that an individual will reject a donor’s marrow.  

Scientists continue to test stem cells as a treatment for HIV, including methods in which cells are taken from a person’s own body and genetically modified, eliminating the need for donor cells. 

CIRM’s Commitment to Investing in Treatments for HIV

The news of the Düsseldorf patient shows the importance of continued stem cell and gene therapy research to find treatments for HIV.  

At the California Institute for Regenerative Medicine (CIRM), we have invested more than $85 million in the search for stem cell and gene therapy treatments for HIV/AIDS, ranging from basic Discovery research to clinical trials.  

Recent CIRM investments include a study at UC Davis health, in which researchers take a patient’s own white blood cells, called T-cells, and modify them so that they can identify and target HIV cells to control the virus without medication. 

CIRM also funded a clinical trial at UCSF to develop a functional cure for HIV/AIDS. In the trial, the team takes a patient’s blood and extracts T cells, a type of immune cell. The T cells are then genetically modified to express two different chimeric antigen receptors (CAR), which enable the newly-created duoCAR-T cells to recognize and destroy HIV infected cells. The modified T cells are then reintroduced back into the patient. 

The goal of this one-time therapy is to act as a long-term control of HIV with patients no longer needing to take ART, in effect a form of HIV cure.  This approach would also address the needs of those who are not able to respond to current approaches, which is estimated to be 50% of those affected by HIV globally. 

Last year, researchers in the UCSF trial shared that they had dosed the first patient in the trial testing their anti-HIV duoCAR-T cell therapy. You can read the announcement here.  

There are approximately 38 million people worldwide living with HIV/AIDS. And each year there are an estimated 1.5 million new cases. The vast majority of those living with HIV do not have access to the life-saving antiretroviral medications that can keep the virus under control. People who do have access to the medications face long-term complications from them including heart disease, bone, liver and kidney problems, and changes in metabolism. 

To learn more about CIRM’s commitment and investments in finding treatments for HIV, visit our website. 

Partners in health

/ Kevin McCormack / 2 Comments
From left to right: Heather Dahlenburg, Jan Nolta, Jeannine Logan White, Sheng Yang
From left to right: Heather Dahlenburg, staff research associate; Jan Nolta, director of the Stem Cell Program; Jeannine Logan White, advanced cell therapy project manager; Sheng Yang, graduate student, Bridges Program, Humboldt State University, October 18, 2019. (AJ Cheline/UC Davis)

At CIRM we are modest enough to know that we can’t do everything by ourselves. To succeed we need partners. And in UC Davis we have a terrific partner. The work they do in advancing stem cell research is exciting and really promising. But it’s not just the science that makes them so special. It’s also their compassion and commitment to caring for patients.

What follows is an excerpt from an article by Lisa Howard on the work they do at UC Davis. When you read it you’ll see why we are honored to be a part of this research.

Gene therapy research at UC Davis

UC Davis’ commitment to stem cell and gene therapy research dates back more than a decade.

In 2010, with major support from the California Institute for Regenerative Medicine (CIRM), UC Davis launched the UC Davis Institute for Regenerative Cures, which includes research facilities as well as a Good Manufacturing Practice (GMP) facility.

In 2016, led by Fred Meyers, a professor in the School of Medicine, UC Davis launched the Center for Precision Medicine and Data Sciences, bringing together innovations such as genomics and biomedical data sciences to create individualized treatments for patients.

Last year, the university launched the Gene Therapy Center, part of the IMPACT Center program.

Led by Jan Nolta, a professor of cell biology and human anatomy and the director of the UC Davis Institute for Regenerative Cures, the new center leverages UC Davis’ network of expert researchers, facilities and equipment to establish a center of excellence aimed at developing lifelong cures for diseases.

Nolta began her career at the University of Southern California working with Donald B. Kohn on a cure for bubble baby disease, a condition in which babies are born without an immune system. The blood stem cell gene therapy has cured more than 50 babies to date.

Work at the UC Davis Gene Therapy Center targets disorders that potentially can be treated through gene replacement, editing or augmentation.

“The sectors that make up the core of our center stretch out across campus,” said Nolta. “We work with the MIND Institute a lot. We work with the bioengineering and genetics departments, and with the Cancer Center and the Center for Precision Medicine and Data Sciences.”

A recent UC Davis stem cell study shows a potential breakthrough for healing diabetic foot ulcers with a bioengineered scaffold made up of human mesenchymal stem cells (MSCs). Another recent study revealed that blocking an enzyme linked with inflammation enables stem cells to repair damaged heart tissue. A cell gene therapy study demonstrated restored enzyme activity in Tay-Sachs disease affected cells in humanized mouse models.

Several cell and gene therapies have progressed to the point that ongoing clinical trials are being conducted at UC Davis for diseases, including sickle-cell anemia, retinopathy, muscle injury, dysphasia, advanced cancer, and Duchenne muscular dystrophy, among others.

“Some promising and exciting research right now at the Gene Therapy Center comes from work with hematopoietic stem cells and with viral vector delivery,” said Nolta.

Hematopoietic stem cells give rise to other blood cells. A multi-institutional Phase I clinical trial using hematopoietic stem cells to treat HIV-lymphoma patients is currently underway at UC Davis.

.Joseph Anderson

Joseph Anderson

“We are genetically engineering a patient’s own blood stem cells with genes that block HIV infection,” said Joseph Anderson, an associate professor in the UC Davis Department of Internal Medicine. The clinical trial is a collaboration with Mehrdad Abedi, the lead principal investigator.

“When the patients receive the modified stem cells, any new immune system cell, like T-cell or macrophage, that is derived from one of these stem cells, will contain the HIV-resistant genes and block further infection,” said Anderson.

He explained that an added benefit with the unique therapy is that it contains an additional gene that “tags” the stem cells. “We are able to purify the HIV-resistant cells prior to transplantation, thus enriching for a more protective cell population.

Kyle David Fink

Kyle David Fink

Kyle David Fink, an assistant professor of neurology at UC Davis, is affiliated with the Stem Cell Program and Institute for Regenerative Cures. His lab is focused on leveraging institutional expertise to bring curative therapies to rare, genetically linked neurological disorders.

“We are developing novel therapeutics targeted to the underlying genetic condition for diseases such as CDKL5 deficiency disorder, Angelman, Jordan and Rett syndromes, and Juvenile Huntington’s disease,” said Fink.

The lab is developing therapies to target the underlying genetic condition using DNA-binding domains to modify gene expression in therapeutically relevant ways. They are also creating novel delivery platforms to allow these therapeutics to reach their intended target: the brain.

“The hope is that these highly innovative methods will speed up the progress of bringing therapies to these rare neurodegenerative disease communities,” said Fink.Jasmine Carter, a graduate research assistant at the UC Davis Stem Cell Program.

Jasmine Carter, a graduate research assistant at the UC Davis Stem Cell Program, October 18, 2019. (AJ Cheline/UC Davis)

Developing potential lifetime cures

Among Nolta’s concerns is how expensive gene therapy treatments can be.

“Some of the therapies cost half a million dollars and that’s simply not available to everyone. If you are someone with no insurance or someone on Medicare, which reimburses about 65 percent, it’s harder for you to get these life-saving therapies,” said Nolta.

To help address that for cancer patients at UC Davis, Nolta has set up a team known as the “CAR T Team.”

Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy in which a patient’s own immune cells are reprogrammed to attack a specific protein found in cancer cells.

“We can develop our own homegrown CAR T-cells,” said Nolta. “We can use our own good manufacturing facility to genetically engineer treatments specifically for our UC Davis patients.”

Although safely developing stem cell treatments can be painfully slow for patients and their families hoping for cures, Nolta sees progress every day. She envisions a time when gene therapy treatments are no longer considered experimental and doctors will simply be able to prescribe them to their patients.

“And the beauty of the therapy is that it can work for the lifetime of a patient,” said Nolta.

Stories of the week – preterm birth and mice with a human immune system

/ Yimy Villa / 2 Comments

While we are here at ISSCR 2019 hearing various scientists talk about their work, we realize that there are various breakthroughs in stem cell research in a wide variety of different fields going on every day. It is wonderful to see how scientists are hard at work in developing the latest science and pushing innovation. Here are two remarkable stories you may have missed this week.

Scientists developing way to help premature babies breathe easier

Researchers at Cincinnati Children’s Hospital Medical Center are looking at ways to stimulate lung development in premature infants who suffer from a rare condition called Bronchopulmonary Dysplasia (BPD), which can cause lifelong breathing problems and even death. Using a mouse model of BPD, extensive analysis, and testing, the scientists were able to create a proposal to develop a stem cell therapy based on what are called c-KIT endothelial progenitor cells.

Premature babies, unable to breathe on their own, rely on machines to help them breathe. Unfortunately, these machines can interfere with lung development as well. The cells proposed in the stem cell therapy are common in the lungs of infants still in the womb and help in the formation of capillaries and air sacs in the lungs called alveoli.

In a press release, Dr. Vlad Kalinichenko, lead investigator for this work, was quoted as saying,

“The cells are highly sensitive to injury by high oxygen concentrations, so lung development in premature babies on mechanical oxygen assistance is impeded. Our findings suggest using c-KIT-positive endothelial cells from donors, or generating them with pluripotent stem cells, might be a way to treat BPD or other pediatric lung disorders associated with loss of alveoli and pulmonary microvasculature.”

The full results were published in American Journal of Respiratory and Critical Care Medicine.

Mice with a human immune system help research into cancer and infections

Speaking of a mouse model, researchers from Aarhus University and Aarhus University Hospital have succeeded in using mice with a transplanted human immune system to study functions in the immune system which are otherwise particularly difficult to study. This work could open the possibilities towards looking further into disease areas such as cancer, HIV, and autoimmune diseases.

Before potential treatments can be tested in humans, there needs to be extensive animal testing and data generated. However, when the disease relate’s to the human immune system, it can be particularly challenging to evaluate this in mice. The research team succeeded in transplanting human stem cells into mice whose own immune system is disabled, and then triggered a type of reaction in the immune system which normally reacts to meeting a range of viruses and bacteria.

In a press release, Dr. Anna Halling Folkmar, one of the researchers behind the study, says that,

“The humanised mice are an important tool in understanding how human immune cells behave during diseases and how they react to different medical treatments.”

The full results were published in Immunology.

CIRM-Funded Scientist is Developing a Stem Cell Therapy that Could Cure HIV

/ Karen Ring / 3 Comments

Photo Illustration by the Daily Beast

This week, UCLA scientist Scott Kitchen made the news for his efforts to develop a CIRM-funded stem cell gene therapy that could potentially cure patients infected with HIV. Kitchen’s work was profiled in the Daily Beast, which argued that his “research could significantly up survival rates from the virus.”

Scott Kitchen, UCLA Medicine

Kitchen and a team of scientists at the UCLA David Geffen School of Medicine are genetically modifying blood-forming, hematopoietic stem cells (HSCs) to express chimeric antigen receptors (CARs) that target HIV-infected cells. CARs are protein complexes on the surface of cells that are designed to recognize specific types of cells and are being developed as powerful immunotherapies to fight cancer and HIV infection.

These CAR-expressing HSCs can be transplanted into patients where they develop into immune cells called T cells and natural killer (NK) cells that will destroy cells harboring HIV. This strategy also aims to make patients resistant to HIV because the engineered immune cells will stick around to prevent further HIV infection.

By engineering a patient’s own blood-forming stem cells to produce an unlimited supply of HIV-resistant immune cells that can also eradicate HIV in other cells, Kitchen and his team are creating the possibility for a life-long, functional cure.

Dr. Kelly Shepard, Senior Science Officer of Discovery and Translation Research at CIRM, reflected on significance of Kitchen’s research in an interview:

Kelly Shepard

“This unique approach represents a two-pronged strategy whereby a patient’s own stem cells are engineered not only to be protected from new HIV infection, but also to produce HIV-specific CAR T cells that will seek out and destroy existing and new pools of HIV infection in that patient, ideally leading to a lifelong cure.”

Kitchen and his team are currently testing this stem cell-based CAR-T therapy against HIV in a large-animal model. Their latest findings, which were published recently in the journal PLOS Pathogens, showed that stem cell-derived human CAR T cells were effective at reducing the amount of HIV virus (called the viral load) in their animal-model. They also saw that the CAR T cells survived for more than two years without causing any toxic side effects. This work was funded by an earlier CIRM award led by another CIRM grantee, Dr. Jerome Zack, who is research collaborator of Kitchen’s.

In December 2017, Kitchen received a $1.7 million CIRM Discovery Stage Quest award so that the team can continue to optimize their stem cell CAR T therapy in animal models. Ultimately, they hope to gain insights into how this treatment could be further developed to treat patients with HIV.

Currently, there is no widely available cure for HIV and standard antiretroviral therapies are expensive, difficult for patients to manage and have serious side effects that reduce life expectancy. CIRM has awarded almost $75 million in funding to California scientists focused on developing novel stem cell-based therapies for HIV to address this unmet medical need. Three of these awards support early stage clinical trials, while the rest support earlier stage research projects like Kitchen’s.

CIRM Communications Director, Kevin McCormack, was quoted at the end Daily Beast article explaining CIRM’s strategy for tackling HIV:

“There are a lot of researchers working on developing stem cell therapies for HIV. We fund different approaches because at this stage we don’t know which approach will be most effective, and it may turn out that it’s ultimately a combination of these approaches, or others, that works.”

Using the AIDS virus to help children battling a deadly immune disorder

/ Kevin McCormack / Leave a comment

Ronnie Kashyap, patient in SCID clinical trial: Photo Pawash Priyank

More than 35 million people around the world have been killed by HIV, the virus that causes AIDS. So, it’s hard to think that the same approach the virus uses to infect cells could also be used to help children battling a deadly immune system disorder. But that’s precisely what researchers at UC San Francisco and St. Jude Children’s Research Hospital are doing.

The disease the researchers are tackling is a form of severe combined immunodeficiency (SCID). It’s also known as ‘bubble baby’ disease because children are born without a functioning immune system and in the past were protected from germs within the sterile environment of a plastic bubble. Children with this disease often die of infections, even from a common cold, in the first two years of life.

The therapy involves taking the patient’s own blood stem cells from their bone marrow, then genetically modifying them to correct the genetic mutation that causes SCID. The patient is then given low-doses of chemotherapy to create space in their bone marrow for the news cells. The gene-corrected stem cells are then transplanted back into the infant, creating a new blood supply and a repaired immune system.

Unique delivery system

The novel part of this approach is that the researchers are using an inactivated form of HIV as a means to deliver the correct gene into the patient’s cells. It’s well known that HIV is perfectly equipped to infiltrate cells, so by taking an inactivated form – meaning it cannot infect the individual with HIV – they are able to use that infiltrating ability for good.

The results were announced at the American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta.

The researchers say seven infants treated and followed for up to 12 months, have all produced the three major immune system cell types affected by SCID. In a news release, lead author Ewelina Mamcarz, said all the babies appear to be doing very well:

“It is very exciting that we observed restoration of all three very important cell types in the immune system. This is something that’s never been done in infants and a huge advantage over prior trials. The initial results also suggest our approach is fundamentally safer than previous attempts.”

One of the infants taking part in the trial is Ronnie Kashyap. We posted a video of his story on our blog, The Stem Cellar.

If the stem cell-gene therapy combination continues to show it is both safe and effective it would be a big step forward in treating SCID. Right now, the best treatment is a bone marrow transplant, but only around 20 percent of infants with SCID have a sibling or other donor who is a good match. The other 80 percent have to rely on a less well-matched bone marrow transplant – usually from a parent – that can still leave the child prone to life-threatening infections or potentially fatal complications such as graft-versus-host disease.

CIRM is funding two other clinical trials targeting SCID. You can read about them here and here.

Stem cell stories that caught our eye: fashionable stem cells, eliminating HIV, cellular Trojan horse fights cancer

/ Karen Ring / 1 Comment

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cell fashion for a cause. Science and art are not mutually exclusive subjects. I know plenty of scientists who are talented painters or designers. But you don’t often see science being displayed in an artistic way or art being used to help explain complex scientific topics. I think that in the future, this will change as both subjects have a lot to offer one another.

Stem cell ties are in fashion!

Stem cell ties are in fashion!

Take this story from the University of Michigan for instance. Designer Dominic Pangborn has joined forces with the Heinz C. Prechter Bipolar Research Fund at the University of Michigan (UOM) to design fashionable scarves and ties featuring beautiful pictures of stem cells. The goal of the Prechter Fund scarf and tie project is to raise awareness for mental health research.

The scarves and ties feature pictures of brain stem cells taken by UOM scientists who are studying them to understand the mechanisms behind bipolar disorder. These stem cells were generated from induced pluripotent stem cells or iPS cells that were derived from donated skin biopsies of patients with bipolar disease. Studying these diseased brain cells in a dish revealed that the nerve cells from bipolar patients were misbehaving, sending out electrical signals more frequently compared to healthy nerve cells.

Dr. Melvin McInnis, the Prechter Fund research director, explained:

“By understanding the causes of bipolar disorder, we will be able to develop new treatments for the illness and most importantly, we’ll be able to prevent destructive mood episodes. Our ultimate goal is to allow people to live happy, normal lives.”

Pangborn is passionate about using art to reflect an important cause.

“I decided to add butterflies to the design because they signify metamorphosis. Our society is finally at a point where mental illness is openly talked about and research is taking a turn for the better.”

He plans to release his collection in time for National Mental Health Awareness month in May. All proceeds will go to the Prechter bipolar research projects at UOM.

Dr. Melvin McInnis, left, and Dominic Pangborn in the Pangborn Design Store in Ann Arbor. (UOM)

Dr. Melvin McInnis, left, and Dominic Pangborn in the Pangborn Design Store in Ann Arbor. (UOM)

New stem cell therapy could eliminate HIV for good

The stem cells therapies being developed to cure HIV are looking more promising every day. A few are already being tested in clinical trials, and CIRM is funding two of them (you can read more about them here). News came out this week about a new trial conducted at the City of Hope’s CIRM Alpha Stem Cell Clinic. They reported in a news release that they’ve treated their first patient. His name is Aaron Kim, and he’s had HIV since he was born. In 1983, he and his twin sister were born prematurely and due to a complication, Aaron had to get a blood transfusion that unfortunately gave him HIV.

Aaron Kim with nurse. (City of Hope)

Aaron Kim with nurse. (City of Hope)

Aaron thought he would live with this disease the rest of his life, but now he has a chance at being cured. In March, Aaron received a transplant of his own bone marrow stem cells that were genetically engineered to have a modified version of the CCR5 gene that makes his cells resistant to HIV infection. CCR5 is a is a protein receptor on the surface of blood cells that acts as a gateway for HIV entry. The hope is that his reengineered stem cells will populate his immune system with HIV-resistant cells that can eliminate the virus completely.

Dr. John Zaia who is the director the the City of Hope Alpha Clinic explained,

“The stem cell therapy Aaron received is one of more than 20 cure strategies for HIV. It may not cure him, but our goal is to reduce or even halt Aaron’s reliance on HIV drugs, potentially eliminating the virus completely.”

My favorite part of this story was that it acknowledged how importance it is for patients to participate in clinical trials testing promising new stem cell therapies where the outcomes aren’t always known. Brave patients such as Aaron make it possible for scientists to make progress and develop better and safer treatments for patients in the future.

Dr. Zaia commented, “It’s a wonderful and generous humanitarian gesture on Aaron’s part to participate in this trial.”

Stem cell Trojan horse fights cancer

Chemotherapy is great at killing cancer cells, but unfortunately, it’s also great at killing healthy cells too. To combat this issue, scientists are developing new delivery methods that can bring high doses of chemotherapy drugs to the cancer tumors and minimize exposure of healthy tissues.

Mesenchymal stem cells loaded with drug-containing microparticles. Credit: Jeff Karp and Oren Levy, Brigham and Women's Hospital

Mesenchymal stem cells loaded with drug-containing microparticles.
Credit: Jeff Karp and Oren Levy, Brigham and Women’s Hospital

A study published this week in Biomaterials, describes a new drug delivery method that has the potential to be an effective treatment for prostate cancer. Researchers from the Brigham and Women’s Hospital and Johns Hopkins University developed a drug delivery platform using mesenchymal stem cells. They packaged a non-active, prodrug version of a potent prostate cancer chemotherapy drug into microparticles that they loaded into MSCs. When the MSCs and prostate cancer cells were cultured together in a dish, the MSCs released their prodrug cargo, which was then internalized by the prostate cancer cells. The prodrug was then metabolized into its active, cancer-killing form and was very effective at killing the cancer cells.

In a news release picked up by Science Daily, one of the lead scientists on the study, Dr. Oren Levy, further explained the stem cell Trojan horse concept:

“Mesenchymal stem cells represent a potential vehicle that can be engineered to seek out tumors. Loading those cells with a potent chemotherapeutic drug is a promising cell-based Trojan horse approach to deliver drugs to sites of cancer.”

If all goes well, the teams plan to develop different versions of their stem cell-based drug delivery method that target different cancers and other diseases.

Stem cell stories that caught our eye: cancer fighting virus, lab-grown guts work in dogs, stem cell trial to cure HIV

/ Karen Ring / 1 Comment

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Cancer fighting virus approved for melanoma

(Disclaimer: While this isn’t a story about stem cells, it’s pretty cool so I had to include it.)

The term “virus” generally carries a negative connotation, but in some cases, viruses can be the good guys. This was the case on Tuesday when our drug approval agency, the US Food and Drug Administration (FDA), approved the use of a cancer fighting virus for the treatment of advanced stage melanoma (skin cancer).

The virus, called T-VEC, is a modified version of the herpesvirus, which causes a number of diseases and symptoms including painful blisters and sores in the mouth. Scientists engineered this virus to specifically infect cancer cells and not healthy cells. Once inside cancer cells, T-VEC does what a virus normally does and wreaks havoc by attacking and killing the tumor.

The beauty of this T-VEC is that in the process of killing cancer cells, it causes the release of a factor called GM-CSF from the cancer cells. This factor signals the human immune system that other cancer cells are nearby and they should be attacked and killed by the soldiers of the immune system known as T-cells. The reason why cancers are so deadly is because they can trick the immune system into not recognizing them as bad guys. T-VEC rips off their usual disguise and makes them vulnerable again to attack.

T-VEC recruits immune cells (orange) to attack cancer cells (pink) credit Dr. Andrejs Liepins/SPL

T-VEC recruits immune cells (orange) to attack cancer cells (pink). Photo credit Dr. Andrejs Liepins/SPL.

This is exciting news for cancer patients and was covered in many news outlets. Nature News wrote a great article, which included the history of how we came to use viruses as tools to attack cancer. The piece also discussed options for improving current T-VEC therapy. Currently, the virus is injected directly into the cancer tumor, but scientists hope that one day, it could be delivered intravenously, or through the bloodstream, so that it can kill hard to reach tumors or ones that have spread to other parts of the body. The article suggested combining T-VEC with other cancer immunotherapies (therapies that help the immune system recognize cancer cells) or delivering a personalized “menu” of cancer-killing viruses to treat patients with different types of cancers.

As a side note, CIRM is also interested in fighting advanced stage melanoma and recently awarded $17.7 million to Caladrius Biosciences to conduct a Phase 3 clinical trial with their melanoma killing vaccine. For more, check out our recent blog.

Lab-grown guts work in mice and dogs

If you ask what’s trending right now in stem cell research, one of the topics that surely would pop up is 3D organoids. Also known as “mini-organs”, organoids are tiny models of human organs generated from human stem cells in a dish. To make them, scientists have developed detailed protocols that sometimes involve the use of biological scaffolds (structures on which cells can attach and grow).

A study published in Regenerative Medicine and picked up by Science described the generation of “lab-grown gut” organoids using intestine-shaped scaffolds. Scientists from Johns Hopkins figured out how to grow intestinal lining that had the correct anatomy and functioned properly when transplanted into mice and dogs. Previous studies in this area used flat scaffolds or dishes to grow gut organoids, which weren’t able to form proper functional gut lining.

Lab-grown guts could help humans with gut disorders. (Shaffiey et al., 2015)

Lab-grown guts could help humans with gut disorders. (Shaffiey et al., 2015)

What was their secret recipe? The scientists took stem cells from the intestines of human infants or mice and poured a sticky solution of them onto a scaffold made of suture-like material. The stem cells then grew into healthy gut tissue over the next few weeks and formed tube structures that were similar to real intestines.

They tested whether their mini-guts worked by transplanting them into mice and dogs. To their excitement, the human and mouse lab-grown guts were well tolerated and worked properly in mice, and in dogs that had a portion of their intestine removed. Even more exciting was an observation made by senior author David Hackham:

“The scaffold was well tolerated and promoted healing by recruiting stem cells. [The dogs] had a perfectly normal lining after 8 weeks.”

The obvious question about this study is whether these lab-grown guts will one day help humans with debilitating intestinal diseases like Crohn’s and IBS (inflammatory bowel disorder). Hackam said that while they are still a long way from taking their technology to the clinic, “in the future, scaffolds could be custom-designed for individual human patients to replace a portion of an intestine or the entire organ.”

Clinical trial using umbilical cord stem cells to treat HIV

This week, the first clinical trial using human umbilical cord stem cells to treat HIV patients was announced in Spain. The motivation of this trial is the previous success of the Berlin Patient, Timothy Brown.

The Berlin patient can be described as the holy grail of HIV research. He is an American man who suffered from leukemia, a type of blood cancer, but was also HIV-positive. When his doctor in Berlin treated his leukemia with a stem cell transplant from a bone-marrow donor, he chose a special donor whose stem cells had an inherited mutation in their DNA that made them resistant to infection by the HIV virus. Surprisingly, after the procedure, Timothy was cured of both his cancer AND his HIV infection.

Berlin patient Timothy Brown. Photo credit: Griffin Boyce/Flickr.

Berlin patient Timothy Brown. Photo credit: Griffin Boyce/Flickr.

The National Organization of Transplants (ONT) in Spain references this discovery as its impetus to conduct a stem cell clinical trial to treat patients with HIV and hopefully cure them of this deadly virus. The trial will use umbilical cord blood stem cells instead of bone-marrow stem cells from 157 blood donors that have the special HIV-resistance genetic mutation.

In coverage from Tech Times, the president of the Spanish Society of Hematology and Hemotherapy, Jose Moraleda, was quoted saying:

“This project can put us at the cutting edge of this field within the world of science. It will allow us to gain more knowledge about HIV and parallel offer us a potential option for curing a poorly diagnosed malignant hematological disease.”

The announcement for the clinical trial was made at the Haematology conference in Valencia, and ONT hopes to treat its first patient in December or January.