University of Utah doctor performs historic first procedure using new technique of retrograde gene therapy on a human heart


Ernie Lively moved to a scenic home in the mountains of Wasatch County to escape the hectic pace of Hollywood when he retired.

The actor, who resides in Heber City with his wife Elain has credentials that include a long list of TV and film appearances, including Passenger 57 and the Sisterhood of the Traveling Pants —the latter that he starred in with his daughter, Blake.

But retirement didn’t provide Lively with the active lifestyle he craved because of simple reality: His heart was failing.  He’d suffered a massive heart attack in 2003, which left him functioning on half a healthy heart.  As time marched on, his ejection fraction —the measurement of the percentage of blood leaving the heart each time it contracts —continued to decline.

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Brown Fat Stem Cells for Treating Diabetes and Obesity


Mammals have two main types of fat: brown fat and white fat.  Brown fat is especially abundant in newborns and in mammals undergoing hibernation.  The primary function of brown fat is to produce body heat so that the animal does not shiver.  In contrast to white fat cells, which contain a single lipid droplet, brown fat cells contain numerous smaller droplets and a higher number of mitochondria, and it is these mitochondria and their high iron content that makes this fat tissue brown.  Brown fat also contains more small blood vessels than white fat, since it has a greater need for oxygen than most tissues.

Recently, researchers at the University of Utah School of Medicine have identified stem cells from brown fat.  The principal researcher of this project, Amit Patel, associate professor of medicine, refuted an old dogma – that adult humans do not possess brown fat.  Children have large amounts of brown fat that is highly metabolically active.  Children can eat a great deal and not gain any weight, relative to adults.  Adults, on the other hand, have an abundance of white fat, and accumulation of white fat leads to weight gain and cardiovascular disease (something not seen in brown fat).  As people age, the amount of white fat increases and the amount of brown fat decreases, which contributes to the onset of diabetes and high cholesterol.

As Patel put it, “If you have more brown fat, you weigh less, you’re metabolically efficient, and you have fewer instances of diabetes and high cholesterol.  The unique identification of human brown fat stem cells in the chest of patients aged 28-34 years is profound.  We were able to isolate the human stem cells, culture and grow them, and implant them into a pre-human model which has demonstrated positive effects on glucose levels.”

In vitro differentiation of brown adipose derived stem cells (BADSCs). (A) Gene expression profile comparing undifferentiated BADSCs to undifferentiated white adipose derived stem cells derived from subcutaneous adipose tissue. Genes in red are associated with brown fat phenotype. (B) Gene expression profile comparing undifferentiated brown adipose derived stem cells to differentiated brown adipocytes. Biological replicates performed in triplicate from a single clone were used for gene expression profile. (C) Transmission electron microscopy of 21 day brown adipocyte differentiation induced with fibronectin type III domain containing 5 (FNDC5) demonstrate multiocular intracytoplasmic lipid vacuoles and mitochondria (arrows). (D) Alizarian red staining of brown adipose derived stem cells induced to undergo osteogenesis. (E) Alcian blue staining of brown adipose derived stem cells directionally differentiated into chondrocytes. (F) Fatty acid binding protein 4 (FABP4) immunocytochemistry of brown adipose derived stem cells induced to undergo white adipogenesis. (G) Undifferentiated BADSCs. (H) Western blot 21 days post FNDC5 induction. Lane 1 brown adipose derived stem cells directionally differentiated into brown adipocytes. Lane 2 non- FNDC5 cells.
In vitro differentiation of brown adipose derived stem cells (BADSCs). (A) Gene expression
profile comparing undifferentiated BADSCs to undifferentiated white adipose derived stem cells
derived from subcutaneous adipose tissue. Genes in red are associated with brown fat phenotype. (B)
Gene expression profile comparing undifferentiated brown adipose derived stem cells to differentiated
brown adipocytes. Biological replicates performed in triplicate from a single clone were used for gene
expression profile. (C) Transmission electron microscopy of 21 day brown adipocyte differentiation
induced with fibronectin type III domain containing 5 (FNDC5) demonstrate multiocular
intracytoplasmic lipid vacuoles and mitochondria (arrows). (D) Alizarian red staining of brown
adipose derived stem cells induced to undergo osteogenesis. (E) Alcian blue staining of brown adipose
derived stem cells directionally differentiated into chondrocytes. (F) Fatty acid binding protein 4
(FABP4) immunocytochemistry of brown adipose derived stem cells induced to undergo white
adipogenesis. (G) Undifferentiated BADSCs. (H) Western blot 21 days post FNDC5 induction. Lane 1
brown adipose derived stem cells directionally differentiated into brown adipocytes. Lane 2 non-
FNDC5 cells.

This new discovery of finding brown fat stem cells may help in identifying potential drugs that may increase the body’s own ability to make brown fat or find novel ways to directly implant brown fat stem cells into patients.

Mesenchymal Stem Cell Transplantation to Heal Mother’s Childbirth Injury


Occasionally. vaginal birth can lead to injury in the mother. Some of these injuries are relatively light and the mother heals rather quickly, but others can be more severe. Stress urinary incontinence (SUI) affects 4-35% of women who have given birth via vaginal delivery. SUI causes unintentional leakage from the bladder during heavy exercise, laughter, coughing, sneezing, heavy lifting, or jumping. SUI can cause discomfort, embarrassment, and some degree of social isolation. Unfortunately the treatments for SUI range from surgery to physiotherapy and they do little good.

In order to provide better options for mothers, researchers at the Cleveland Clinic’s Department of Biomedical Engineering have used female rats with birth-induced injuries as a model system. In this model system, injections of mesenchymal stem cells improved recovery from childbirth-induced injuries.

Previous work by this research group showed that injected mesenchymal stem cells tended to move into the spleen. However, if the urethra and vagina were damaged by childbirth trauma prior to mesenchymal stem cell injections, the cells targeted the damaged tissues and secreted trophic factors, which stimulated the differentiation and survival of remaining cells, and also induced the mesenchymal stem cells to engraft into the smooth muscles around the urethra and vagina. These activities accelerated and improved recovery of the animals from SUI.

Margot S. Damaser from the Cleveland Clinic said, “Stem cell-based therapy has recently gained attention as a promising treatment for SUI. Stem cell therapies may be more feasible and less invasive than current therapies.”

Other kinds of stem cells have been used to experimentally treat SUI in laboratory animals. Autologous or self-donated muscle stem cells have been used to treat SUI in animals and in human clinical trials. Fat-based stem cells have also been used, but only in animal models.

Damaser believes that mesenchymal stem cells have the added advantage of not being recognized by the immune system and therefore the possibility to implanting stem cells from an unrelated donor is a possibility for older patients.

“Since rat MSCs were used in this study, the results can only be applied to rat models of injury-treated rats,: said Damaser. “Human adult stem cells need to be investigated in future studies to see if these findings also apply to humans.”

Other researchers think that this procedure might serve as a treatment for SUI in older women. “This study provides evidence that mesenchymal stem cell transplantation could favorably impact a side effect of delivery and aging by releasing factors that can influence the urethra and vagina to treat stress urinary incontinence,” said Amit N Patel, director of cardiovascular regenerative medicine at the University of Utah. “Further studies are required to confirm that this animal study translates to humans.”