Safe Stem Cells Reverse Alzheimer’s Symptoms

 Scientists in South Korea have used intravenous injections of human adipose-derived stem cells (hADSCs) to both prevent development of and reverse the symptoms and neuropathology of Alzheimer’s disease (AD) in mouse models. The studies, in the Tg2576 mouse model of AD, demonstrated that either intravenous or intracerebral injections of hASCs led to significant improvements in memory and learning, and reduced the numbers of amyloid plaques and Aβ levels in the brain. The benefits were evident for at least four months after treatment.

Prior in vivo studies have demonstrated that transplanted neural stem cells and bone marrow-derived mesenchymal stem cells can help rescue memory deficits in AD mouse models and hold back Aβ deposition, but neither of these stem cell types would be suitable for intravenous administration, according to Seoul National University’s Yoo-Hun Suh, Ph.D., and the RNL Bio Stem Cell Technology Institute’s Jeong-Chan Ra, Ph.D. Another source of stem cells is the adipose tissue, which yields adipose-derived stem cells, a mesenchymal stem cell type that can differentiate into both mesenchymal and non-mesenchymal lineages. In contrast with other stem cell types, autologous hASCs are not associated with ethical issues, and, based on data from the team’s previous research, can be administered intravenously with no concerns about immune rejection or tumorigenesis.

In the first known study of its kind, the Seoul researchers have now shown not only that intravenously administered hASCs can traverse the blood-brain-barrier and engraft in the brain, but that either intravenous or intracerebral therapy hASC therapy results in dramatic cognitive improvements in Alzheimer’s disease mice. These benefits were associated with reduced numbers of amyloid plaques and decreased levels of Aβ and amyloid precursor protein C-terminal fragment (APP-CT) through the induction of neprilysin, which hydrolyzes toxic proteins. Critically, when the hASCs were administered intravenously to in young AD mice, the treatment completely prevented plaque formation. 

Further analyses showed that intravenous and intracerebral administration of the stem cells was associated with increased brain levels of IL-10 and neurotrophic factors, including VEGF and GDNF, which directly suppressed neuronal cell death. In vitro studies indicated that the hASCs themselves produced IL-10, and stimulated additional IL-10 production by microglial cells. And when transplanted directly into the brain, the hASCs tinduced cell division and neurodifferentiation of endogenous neuroprogenitors in the hippocampus, and stabilized dendrites and synapses.

“We conclude that intracerebrally or intravenously injected hASCs dramatically improved learning and memory ability and neuropathology of Tg2576 mice by diminishing the formation of amyloid plaques, decreasing Aβ and C-terminal levels and upregulating IL-10, VEGF, and elevating endogenous neurogenesis and synaptic and dendritic stability,” the authors researchers conclude. “Although it is yet unclear how hASCs upregulated IL-10 and growth factors such as VEGF and GDNF, our findings that intravenously transplanted hASCs prevent the onset and progression of the disease clearly provide an important preclinical platform for the development of prevention and therapy for AD patients.”

 

Source: Genetic Engineering & Biotechnology News

Stem cells in cord blood show promise for treating bowel disease

Researchers have found a special population of stem cells in cord blood that has the innate ability to migrate to the intestine and contribute to the cell population there, suggesting the cells’ potential to treat inflammatory bowel disease (IBD).  

These cells are involved in the formation of blood vessels and may prove to be a tool for improving the vessel abnormalities found in IBD, said lead author Graca Almeida-Porada, M.D., Ph.D., a professor at Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine.

IBD, which is characterized by frequent diarrhea and abdominal pain, actually refers to two conditions – ulcerative colitis and Crohn’s disease – in which the intestines become red and swollen and develop ulcers.

With IBD, blood vessels in the intestine leak and contribute to inflammation.

While there is currently no cure for IBD, there are drug therapies aimed at reducing inflammation and preventing the immune response. However, these therapies aren’t always effective. The long-term aim of the research is to develop an injectable cell therapy to induce tissue recovery.

The work, performed while Almeida-Porada was at the University of Nevada, also involved colleagues from Indiana University School of Medicine.

The researchers studied a special population of cells, known as endothelial colony-forming cells, found in cord blood, bone marrow and circulating blood. The finding in 1997 that the cells can contribute to blood vessel formation in adults, not just embryos, initiated the notion of using them for therapy. Studies in humans have validated the ability of these cells to improve reduced blood flow to the limbs and to treat heart diseases.

However, there have been few studies to explore the inherent biologic ability of these cells to home to different organs and contribute to tissue-specific cell populations. Evaluating their potential to migrate to the intestine was an obvious choice, said Almeida-Porada, because dysfunctional blood vessels are a hallmark of IBD.

Not only are circulating levels of vessel-forming cells reduced in patients with IBD, but a key factor in IBD progression is the development of abnormal or immature blood vessels, which leads to chronic inflammation.

The cells were injected into fetal sheep at 59 to 65 days gestation. About 11 weeks later, intestinal tissue was analyzed to detect the presence of the human cells. The researchers found that the human cells had migrated to the intestine and contributed significantly to the cell population there.

“This study shows that the cells can migrate to and survive in a healthy intestine and have the potential to support vascular health. Our next step will be to determine whether the cells can survive in the ‘war’ environment of an inflamed intestine,” said Almeida-Porada.

The researchers also evaluated the ability of the cells to home to the liver. Smaller numbers of cells reached the liver than the intestine, suggesting that new strategies would be needed to enhance the therapeutic potential for this organ.

The research has been published in the current print issue of the journal Hepatology. (ANI)

 

Source: News Track India

University of Maryland study: Neonatal heart stem cells may help mend kids’ broken hearts

 Researchers at the University of Maryland School of Medicine, who are exploring novel ways to treat serious heart problems in children, have conducted the first direct comparison of the regenerative abilities of neonatal and adult-derived human cardiac stem cells. Among their findings: cardiac stem cells (CSCs) from newborns have a three-fold ability to restore heart function to nearly normal levels compared with adult CSCs. Further, in animal models of heart attack, hearts treated with neonatal stem cells pumped stronger than those given adult cells. The study is published in the September 11, 2012, issue of Circulation.

“The surprising finding is that the cells from neonates are extremely regenerative and perform better than adult stem cells,” says the study’s senor author, Sunjay Kaushal, M.D., Ph.D., associate professor of surgery at the University of Maryland School of Medicine and director, pediatric cardiac surgery at the University of Maryland Medical Center. “We are extremely excited and hopeful that this new cell-based therapy can play an important role in the treatment of children with congenital heart disease, many of whom don’t have other options.”

Dr. Kaushal envisions cellular therapy as either a stand-alone therapy for children with heart failure or an adjunct to medical and surgical treatments. While surgery can provide structural relief for some patients with congenital heart disease and medicine can boost heart function up to two percent, he says cellular therapy may improve heart function even more dramatically. “We’re looking at this type of therapy to improve heart function in children by 10, 12, or 15 percent. This will be a quantum leap in heart function improvement.”

Heart failure in children, as in adults, has been on the rise in the past decade and the prognosis for patients hospitalized with heart failure remains poor. In contrast to adults, Dr. Kaushal says heart failure in children is typically the result of a constellation of problems: reduced cardiac blood flow; weakening and enlargement of the heart; and various congenital malformations. Recent research has shown that several types of cardiac stem cells can help the heart repair itself, essentially reversing the theory that a broken heart cannot be mended.

Stem cells are unspecialized cells that can become tissue- or organ-specific cells with a particular function. In a process called differentiation, cardiac stem cells may develop into rhythmically contracting muscle cells, smooth muscle cells or endothelial cells. Stem cells in the heart may also secrete growth factors conducive to forming heart muscle and keeping the muscle from dying.

To conduct the study, researchers obtained a small amount of heart tissue during normal cardiac surgery from 43 neonates and 13 adults. The cells were expanded in a growth medium yielding millions of cells. The researchers developed a consistent way to isolate and grow neonatal stem cells from as little as 20 milligrams of heart tissue. Adult and neonate stem cell activity was observed both in the laboratory and in animal models. In addition, the animal models were compared to controls that were not given the stem cells.

Dr. Kaushal says it is not clear why the neonatal stem cells performed so well. One explanation hinges on sheer numbers: there are many more stem cells in a baby’s heart than in the adult heart. Another explanation: neonate-derived cells release more growth factors that trigger blood vessel development and/or preservation than adult cells.

“This research provides an important link in our quest to understand how stem cells function and how they can best be applied to cure disease and correct medical deficiencies,” says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs, University of Maryland; the John Z. and Akiko K. Bowers Distinguished Professor; and dean, University of Maryland School of Medicine. “Sometimes simple science is the best science. In this case, a basic, comparative study has revealed in stark terms the powerful regenerative qualities of neonatal cardiac stem cells, heretofore unknown.”

Insights gained through this research may provide new treatment options for a life-threatening congenital heart syndrome called hypoplastic left heart syndrome (HLHS). Dr. Kaushal and his team will soon begin the first clinical trial in the United States to determine whether the damage to hearts of babies with HLHS can be reversed with stem cell therapy. HLHS limits the heart’s ability to pump blood from the left side of the heart to the body. Current treatment options include either a heart transplant or a series of reconstructive surgical procedures. Nevertheless, only 50-60 percent of children who have had those procedures survive to age five.

According to the American Heart Association, congenital heart disease may affect approximately one in 100 children. In the United States, more than 1 million adults are living with congenital heart defects.

 

Source: Science Index, University of Maryland Medical Center

Colorado State College of Veterinary Medicine studies chronic kidney disease in cats

Cats with failing kidneys are wanted for a study which will look at how stem cells can help treat renal failure, otherwise known as chronic kidney disease.  

Stem cells used in the study are extracted from the fat of research cats, according to Dr. Jessica Quimby. The fat is then grown in a lab, where it is expanded to the amount of cells needed.

Some benefits of the stem cells will make for better renal function and lessened kidney inflammation, according to a press release.

Quimby said that the stem cells will treat the actual problem — inflammation — while current methods only take care of side effects.

The study consists of five appointments for participating felines. The first and fifth appointments are a Glomerular Filtration Rate (GFR) test to assess kidney function. The other three consist of intravenous stem cell injections.

A smaller group of cats would act as a control group and receive a placebo drug, according to the press release. This group can choose to get stem cells after the study’s conclusion.

“[The] treatment is well tolerated by the cats and that they stay one day in our area specified for cats only,” said veterinary technician and research assistant Amber Caress. “They need to come in multiple times for treatment but the few owners that I have spoken to seem very excited to have their cats participate in such a cutting edge study.”

In the previous two trials cats experienced nausea and quick breathing during the intravenous procedure. In the current trial, however, Quimby said the cats “seem to tolerate it pretty well.”

Participation is open to 20 cats and will remain so until all spots are taken or until the grant’s end one-and-a-half years from now. Elderly cats with chronic kidney disease who don’t have other illnesses or conditions will be accepted.

“It really is a unique opportunity,” Quimby said.

Stem cells are blank cells which can be used to “regenerate and repair diseased and damaged cells,” according to the Mayo Clinic.

Chronic kidney disease, or renal failure, occurs when the kidneys cease their natural function of ridding the body of waste and retaining water.

“It’s the opposite of what kidneys are supposed to do,” veterinarian Heidi Patterson said.

Current methods of treating renal failure include intravenous (IV) fluids and subcutaneous fluids, which are administered under the skin, to replace lost hydration. Phosphate binders to suppress excess phosphate in the body and appetite stimulants are also used.

Symptoms of the condition include “increased drinking, urination, weight loss and decreased appetite” according to Patterson.

The study is funded by a grant from the Morris Animal Foundation with support from Frankie’s Fund for Feline Stem Cell Research.

 

Source: Devin O’Brien, The Rocky Mountain Collegian