All comments by Macarena Campos

Benefits of cord blood transplantation include low rates of relapse and chronic graft-versus-host disease (GVHD). However, the use of cord blood is rapidly declining because of the high incidence of infections, severe acute GVHD, and transplant-related mortality. UM171, a haematopoietic stem cell self-renewal agonist, has been shown to expand cord blood stem cells and enhance multilineage blood cell reconstitution in mice. We aimed to investigate the safety and feasibility of single UM171-expanded cord blood transplantation in patients with haematological malignancies who do not have a suitable HLA-matched donor.

This single-arm, open-label, phase 1–2 safety and feasibility study was done at two hospitals in Canada. The study had two parts. In part 1, patients received two cord blood units (one expanded with UM171 and one unmanipulated cord blood) until UM171-expanded cord blood demonstrated engraftment. Once engraftment was documented we initiated part 2, reported here, in which patients received a single UM171-expanded cord blood unit with a dose de-escalation design to determine the minimal cord blood unit cell dose that achieved prompt engraftment. Eligible patients were aged 3–64 years, weighed 12 kg or more, had a haematological malignancy with an indication for allogeneic hematopoietic stem cell transplant and did not have a suitable HLA-matched donor, and a had a Karnofsky performance status score of 70% or more.

Our preliminary findings suggest that UM171 cord blood stem cell expansion is feasible, safe, and allows for the use of small single cords without compromising engraftment. UM171-expanded cord blood might have the potential to overcome the disadvantages of other cord blood transplants while maintaining the benefits of low risk of chronic GVHD and relapse, and warrants further investigation in randomised trials.

MORE INFO www.thelancet.com/journals/lanhae/article/PIIS2352-3026(19)30202-9/fulltext

Intravenous infusion of banked autologous and sibling umbilicalcord blood (CB) is being studied in children with acquired neu-rological conditions and has demonstrated safety and feasibilityin phase I/II studies. To provide access to this investigationalprocedure while efficacy trials are conducted, an expandedaccess program (EAP) was developed.

More than 1,400 children have enrolled in the screening protocol to date. From November 2017 to June 2019, 276 children received 302 CB infusions under the EAP.

No child required treatment or developed an infection post-infusion. One-year follow-up questionnaires were completed by 54 of 83 (65%) families. Parental assessment of clinical improvements varied.

MORE INFO stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/sctm.12583

autismcenter.duke.edu

A study released in STEM CELLS Translational Medicine provides compelling evidence of how an injection of human amniotic fluid stem cells can be used to protect the spinal cord of a fetus from myelomeningocele (MMC).

The finding could lead to a new strategy for treating this debilitating birth defect that affects about 1 out of every 4,000 children born in the United States each year.

The most severe form of spinal bifida, myelomeningocele results when the backbone and spinal canal do not close before birth. It can leave a child with many disabilities, including partial or full paralysis, difficulty with bowel and bladder control, hydrocephalus and developmental delay.

“Despite the poor prognosis associated with MMC, the options for prenatal treatments are still limited,” said the study’s lead investigator, Daigo Ochiai, M.D., Ph.D., of the Keio University School of Medicine, Tokyo, Japan. “Recently, however, cellular therapy delivered to the fetus while in the womb has shown promise for treating birth defects.

“This led us to investigate whether human amniotic fluid stem cells (hAFSCs) might be used to treat fetal MMC, especially since fetal MMC can be diagnosed during an early stage of pregnancy and this gives us an opportunity to isolate hAFSCs from those patients and use them for in utero therapy. To the best of our knowledge, this is the first study to do this,” he added.

Pregnant rats were treated to induce fetal MMC, then injected with hAFSCs in each amniotic cavity. “Overall, we examined 116 rat fetuses with MMC,” said Dr. Ochiai. “Results showed that the hAFSCs exerted their effect on fetal MMC via two different mechanisms: by migrating to the lesions and covering the exposed spinal cords, and by secreting hepatocyte growth factor to protect neural elements and promote neural regeneration.”

Yushi Abe, M.D., also of Keio University School of Medicine, was first author of the study. “MMC is a disease that causes many disorders, but there is no effective treatment,” he noted. “This study shows us that in utero therapy with hAFSCs may be an innovative treatment for fetal MMC. As such, we would like to continue research for human clinical application in the future.”

MORE INFO stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/sctm.19-0002

An 8-month-old girl who had severe combined immune deficiency (SCID) underwent a successful hematopoietic stem cell transplant surgery at the Children’s Hospital of Fudan University in Shanghai; the stem cell was taken from umbilical cord blood.

The baby girl, identified by the hospital as Ranbao, started to develop symptoms including cough, fever, swollen lymph node and lung infection soon after she was born in July. Her parents took her to the hospitals in Hunan province and Chongqing municipality but were not able to determine the cause.

The operation involves injecting the stem cells into the body to help restore immune system. Cord blood hematopoietic stem cells transplantation has become one of the most effective treatments for the hematological and immune diseases.

SOURCE: www.chinadaily.com.cn

The baby girl Zhao Jiaxin was the first child in China to receive a cord blood transplant as a cure for a genetic form of irritable bowel disease that is often lethal to newborns.
 
Born in early 2015, baby Zhao began suffering from diarrhea and fever when she was just 8 days old. These same symptoms had led to the death of her older sister at age 5 months. “We feared so much that we might lose her, too,” said her mother Ji Jiannan. Zhao’s father, Zhao Mingwei, said: “Our first daughter succumbed to the disease, so when Yuanyuan (Zhao’s nickname) started showing the same symptoms when she was just a week old, we were terrified.” Zhao‘s family lives in the Chinese province of Henan. After failing to find help at local clinics, her parents took her to the Children’s Hospital of Fudan University in Shanghai. It was there that genetic testing revealed that Zhao had a Very Early Onset form of Irritable Bowel Disease (VEO-IBS) that is caused by an inherited genetic mutation.
 
A deficiency in the gene for the immunosuppressive cytokine interleukin-10 leads to severe dysregulation of the immune system in the intestines. First reported1 in 2009, children with VEO-IBS from IL10RA immune deficiency are not only severely malnourished but often have intestinal abscesses and fistulas. “The only effective treatment is a stem cell transplant” explained Huang Ying, MD PhD, the director of the digestive disease department at Children’s Hospital of Fudan University. “It can help to repair the genetic deformity and control the symptoms of the disease,” she said. Baby Zhao became the first of 9 patients over 2 years to receive cord blood transplants at Children’s Hospital of Fudan University for VEO-IBS with IL10RA immune deficiency2. The patients ranged in age from 6 to 43 months and in weight from 3 to 10.4 kg. The transplants were performed with reduced intensity chemotherapy conditioning, so there was less toxicity for infant patients already suffering from malnutrition and infections of the intestines. Patients experienced normal stools within 1 to 3 months after engraftment of the transplant. Chinese newspapers covered the story when baby Zhao went home in Nov. 2015. Her happy mother exclaimed, “I remember when she was 100 days old, she was skinny like a skeleton. Now look at her: She’s almost got a puffy face.”
 

Epileptic seizures could be halted by injecting stem cells into the brain, scientists claim. Researchers have developed a new treatment, which involves converting skin cells into stem cells – which can turn into any type. 

The converted stem cells, designed to dampen down the effects of seizures, are then implanted back into the brain. The scientists behind the study, at Texas A&M University, aimed to boost the number of inhibitory cell to try and combat seizures.

They injected rats with a chemical, called clozapine-N-oxide, that triggered spontaneous seizures starting in the hippocampus – located in the middle part of the brain. 

Dr Dinesh Upadhya and colleagues then implanted inhibitory brain cells, called stem cell-derived GABA-ergic progenitor cells, into half of the rats and watched what happened. Five months later, the rats were having up to 70 per cent fewer seizures, compared to the rats who did not have the treatment. 

Dr Ashok Shetty, who was an author in the study, told MailOnline: ‘In other words, they can no longer fire action potentials. The methodology employed for silencing transplant-derived neurons in the current study is called chemogenetic approach.’

The implanted cells had survived in the hippocampus – a region usually associated with memory, dissections later showed. The treatment could be suitable for people whose seizures start in the hippocampus.  

SOURCE: www.dailymail.co.uk (01/2019)

An international study published in the journal Blood by researchers led by Dr. Elie Haddad, a pediatric immunologist and researcher at CHU Sainte-Justine and professor at Université de Montréal, highlights the urgent need to develop better treatment strategies for patients suffering from severe combined immune deficiency (SCID).

This deficiency, better known as “bubble baby disease” is a rare syndrome characterized by a total non-function of the body’s immune system. The children affected have no immune defence and are vulnerable to bacteria, viruses and fungi, resulting in repeated severe infections. Without appropriate treatment, in most cases this disease is fatal within the first months after birth.

SCID can be caused by mutations in various genes involved in the functioning of the immune system. The new research shows that the nature of the mutated gene (or genotype) has a significant influence on patients’ survival and reconstitution of their immune system after bone marrow transplant. According to the study, the genotype must be taken into account when adapting treatment strategies to individual patients.

The results showed that survival rates of patients were higher after a cell transplant from a matched sibling donor. In recipients from other donor types, which represent 86 per cent of cases, the data showed that the SCID genotype had a strong influence on survival and immune reconstitution. In addition, the researchers found that young age and absence of active infection at the time of transplant were also key factors for survival, and both were significantly associated with improved survival following a transplant.

SOURCE:  nouvelles.umontreal.ca (11/2018) / www.bloodjournal.org

Performed as part of reconstructive surgery when the infant is a few months old, the stem cell procedure provides good results in growing new bone to close the upper jaw cleft — and may avoid the need for later bone graft surgery, according to the case report by Alejandro Garcia Botero, MD, of Hospital De San José, Bogota, Colombia, and colleagues.

Dr. Botero and colleagues report their experience with the stem cell procedure in an infant with cleft lip and palate, diagnosed by ultrasound before birth. The baby girl had an alveolar cleft, involving an area of bone where teeth are located.

Immediately after delivery, a sample of the infant’s umbilical cord blood was collected to isolate stem cells, which were processed and frozen to preserve them for later use. Umbilical cord blood is a rich source of various types of stem cells, which have the potential to develop into many different types of specialized cells, including bone and cartilage.

“Since the age is that of the newborn, have a greater potential to regenerate the organism,” Dr. Botero and coauthors write. For the first few months, the infant underwent a nonsurgical “nasoalveolar shaping” procedure to align the soft tissues of the upper jaw.

At age five months, the stem cells were thawed for use as part of “boneless bone grafting” surgery (gingivoperiostioplasty). The stem cells were placed in a pocket of soft tissue bridging the gap in the upper jaw. A small piece of absorbable biomaterial (Gelfoam) was used a scaffold to guide growth of new bone across the cleft palate. This procedure was performed at the same time as surgery to correct the cleft lip (cheiloplasty).

Follow-up confirmed formation of new bone to close the cleft palate, providing good position and support for normal eruption of the teeth. Imaging scans when the patient was five years old showed good thickness of the upper jaw bone in the area where the cleft had been.

SOURCE: sciencedaily.com (10/2018)

According to the Duke Center for Autism, “previous research has shown that cord blood cells can help reduce inflammation and signal cells to help repair damaged brain areas. The goal of this study was to investigate whether similar success will be shown in children with ASD.”

“But the study is blinded, so no one knows what their child received or what order,” said Kurtzberg.

This is Duke’s second phase of this trial and these results won’t be analyzed until next fall; however, the trial’s first phase, which is already complete, showed promising results for the children with autism who participated in the study.

“And we found that about 70 percent of the children improved getting their own cord blood,” said Kurtzberg. If this second trial also shows that cord blood is beneficial, Duke will work with the FDA to expedite approval of this treatment for all children.

One of the families that participe in this study said that her family is grateful and humbled by being chosen to take part in this medical trial, and they hope the results will one day be able to help all families dealing with autism.

ORIGINAL SOURCE nbcdfw.com (July 2018)

LINK TO CLINICAL TRIAL clinicaltrials.gov/ct2/show/NCT03327467

Four-year-old Wyatt Haney has been fighting for his life since the day he was born at a Joplin, Mo., hospital. 11 months after he was born, Wyatt’s family and his medical team had an answer—TPI, or triosephosphate isomerase deficiency. TPI is an extremely rare genetic multisystem disorder first identified in 1964. Since that time, only 100 patients have been diagnosed worldwide, and only four are living today. Wyatt is one of those four.

Patients with TPI lack the enzyme necessary to break down certain sugars in the body. In addition to hemolytic anemia, they also experience severe, progressive neurologic and cardiac symptoms.

The disorder is inherited. Both Amanda and her husband, Bobby, are carriers, but their other two children are unaffected.

With the TPI diagnosis in hand, Dr. Sharma referred Wyatt and his family to Doug Myers, MD, a pediatric hematologist/oncologist with expertise in bone marrow transplant at Children’s Mercy.

After carefully weighing the pros and cons of transplant with the BMT team, Amanda and Bobby agreed this was Wyatt’s best chance for long-term survival. On Nov. 1, 2014, Wyatt was admitted to Children’s Mercy for chemotherapy to suppress his immune system for the transplant. On Nov. 12, he received his first bone marrow transplant from an anonymous donor.

A few weeks later testing revealed Wyatt’s transplant was failing. That’s when Dr. Myers suggested a second transplant using the donor’s peripheral blood cells but again, Wyatt’s immune system rejected the transplant.

Then Wyatt got very ill and was admitted to the hospital. A few days later, he was transferred to the Children’s Mercy Pediatric Intensive Care Unit with a life-threatening infection.

After getting the infection under control, Dr. Myers recommended a different option for Wyatt, a transplant using cord blood.

By this time, Wyatt’s immune system was worn down, reducing the odds of rejection. On May 5, 2015, Wyatt’s family and friends prayed the third time would be a charm, and their prayers were answered. “Wyatt’s body accepted the cord blood transplant” Amanda said.

Finally, Wyatt was on the road to recovery. Four months after being admitted to the hospital, he was ready to head home to Galena. Though it’s possible other TPI patients have been successfully treated with blood-forming stem cells, based on literature searches, it appears Wyatt may be the first and only one in the world to survive.

SOURCE and PHOTO news.childrensmercy.org