Monthly Archives: September 2014

The same remedy that healed journalist Julia Szabo's dog wound up saving her life.

Part of Szabo's book, "Medicine Dog: The Miraculous Cure that Healed My Best Friend and Saved My Life" (Lyon's Press, Guilford, CT, 2014; $16.47), is devoted to a black pit bull who found a sort of fountain of youth through stem cell therapy. Another portion focuses on how a similar therapy may have saved Szabo's own life.

Szabo says she purposefully intended to adopt a black pit bull from animal care and control in New York City because such a dog might otherwise never be adopted. It's true that black dogs of any breed are least likely to find homes, and dogs that resemble pit bulls aren't for everyone. Like most municipal animal control facilities, New York's is inundated with pits.

She recalls that when she first saw Sam, "He reached out his big bear-like paw, and I took it to my heart. It turned out the decision to adopt Sam was the best choice of my life." Sam was the "perfect dog," he adds, though large at 75 lbs. He was about a year old when adopted in 1996.

As the years passed, Sam became increasingly arthritic. Things got so bad that he could barely lift his leg to relieve himself. Szabo was treating Sam as her veterinarian suggested, but he continued to decline. One day, Sam collapsed on the street. Thing is - though he was about 14, aside from the arthritis, Sam was otherwise healthy.

Desperate to try anything, via Google, Szabo discovered Vet-Stem, a company that provides regenerative stem cell therapy for animals.

"It's an amazing thing," Szabo says, "While people in Europe know about this (treatment) and accept it, most Americans think embryonic stem cells (come) from aborted fetuses, but this isn't it; these stem cells are carried in belly fat. This is a case of loving fat."

Sam shortly after stem cell treatment

Under anesthesia, the animal undergoes liposuction, literally a tummy tuck. The fatty or adipose tissue is overnighted to Vet-Stem in San Diego, CA., where it's processed in a centrifuge to separate the stem cells from the fat. Then, the stem cells are placed in vials and delivered to the veterinarian on dry ice. The cells are then directly injected into the pet's arthritic joints and intravenously into the bloodstream.

"It's like the movie 'Fantastic Voyage,' where they shrink down the scientists into a tiny little capsule and go through the guy's bloodstream," says Szabo. "The stem cells naturally target places in the body that are inflamed and need an assist. In Sam's case, they went right to his inflamed joints, and it worked."

The rest is here:
Stem Cell Therapy Save Her Dog, And Saved Her | Steve Dale ...

Research has shown that cells called induced pluripotent stem cells (iPSCs) may hold the potential to cure damaged nerves, regrow limbs and organs, and also model a patient's particular disease.

When the generation of iPSCs was first reported in 2006, efficiency was paramount because only a fraction of a percentage of reprogrammed cells successfully became cell lines. Accordingly, the stem cell field focused on reprogramming efficiency to boost the pool of cells that could be studied. However, as scientists gained an increased understanding of the reprogramming process, they realized that myriad variables, including the ratio of reprogramming factors and the reprogramming environment, can also greatly affect cell quality.

Now researchers working in the lab of Whitehead Institute Founding Member Rudolf Jaenisch together with scientists from the Hebrew University have determined that the reprogramming factors themselves impact the reprogramming efficiency and the quality of the resulting cells. Their work is described in the current issue of the journal Cell Stem Cell.

"Postdoctoral researcher Yosef Buganim and Research Scientist Styliani Markoulaki show that a different combination of reprogramming factors may be less efficient than the original, but can produce much higher quality iPSCs," says Jaenisch, who is also a professor of biology at MIT. "And quality is a really important issue. At this point, it doesn't matter if we get one colony out of 10,000 or one out of 100,000 cells, as long as it is of high quality."

To make iPSCs, scientists expose adult cells to a cocktail of genes that are active in embryonic stem cells. iPSCs can then be pushed to differentiate into almost any other cell type, such as nerve, liver, or muscle cells. Although the original combination of Oct4, Sox2, Klf4, and Myc (OSKM) efficiently reprograms cells, a relatively high percentage of the resulting cells have serious genomic aberrations, including aneuploidy, and trisomy 8, which make them unsuitable for use in clinical research.

Using bioinformatic analysis of a network of 48 genes key to the reprogramming process, Buganim and Markoulaki designed a new combination of genes, Sall4, Nanog, Esrrb, and Lin28 (SNEL). Roughly 80% of SNEL colonies made from mouse cells were of high quality and passed the most stringent pluripotency test currently available, the tetraploid complementation assay. By comparison, only 20-30% of high quality OSKM passed the same test. Buganim hypothesizes that SNEL reprograms cells better because, unlike OSKM, the cocktail does not rely on a potent oncogene like Myc, which may be causing some of the genetic problems. More importantly, the cocktail does not rely on the potent key master regulators Oct4 and Sox2 that might abnormally activate some regions in the adult cell genome.

To better understand why some reprogrammed cells are of high quality while others fall short, Buganim and Markoulaki analyzed SNEL colonies down to the genetic and epigenetic level. On their DNA, SNEL cells have deposits of the histone protein H2AX in locations very similar to those in ESCs, and the position of H2AX seems to predict the quality of the cell. The researchers believe this characteristic could be used to quickly screen for high quality colonies.

But for all of its promise, the current version of SNEL seems unable to reprogram human cells, which are generally more difficult to manipulate than mouse cells.

"We know that SNEL is not the ideal combination of factors," says Buganim, who is currently a Principal Investigator at Hebrew University in Jerusalem. "This work is only a proof of principle that says we must find this ideal combination. SNEL is an example that shows if you use bioinformatics tools you can get better quality. Now we should be able to find the optimal combination and try it in human cells to see if it works."

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Therapy-Grade Induced Pluripotent Stem Cells can be ...