Mesenchymal Stem Cells Treating Fecal Incontinence in Animals

A new study published by the journal STEM CELLS Translational Medicine has demonstrated the regenerative effects of mesenchymal stem cells (MSC) on the anal sphincter. This work could have implications for the 11 percent of the population who suffer from fecal incontinence as a result of injury or disease.

Massarat Zutshi, M.D., and Levilester Salcedo, M.D., led the research team made up of their colleagues at the Cleveland Clinic (Cleveland, Ohio) and Summa Cardiovascular Institute and Northeast Ohio Medical University (Akron, Ohio).

Unfortunately none of the present treatments for fecal incontinence “are efficacious in the long-term or without complications related to the surgery or the device,” explained Dr. Zutshi. Additionally, she noted that mesenchymal stem cells (MSCs) from adipose tissue and skeletal muscle have improved heart function and urinary sphincter in animal models, On the strength of these successes, Zutshi and her colleagues decided to use these cells to treat damaged anal sphincters.

In this study. Zutshi and Salcedo and their research teams used a single intramuscular (IM) injection of MSCs compared to a series of intravenous (IV) treatments. For these experiments, they employed rats that had undergone an excision of 25 percent of their anal sphincter complex. 24 hours after anal sphincter injury, one group received a single IM injection of stem cells directly into their anal sphincters. A second group began a series of six consecutive daily treatments delivered by IV through their tail veins, as did a group of non-injured animals. A third group of injured animals received no stem cells.

The scientists measured anal pressures in these animals. Accordingly, they measured anal pressures were recorded prior to injury, then again at 10 days and five weeks after treatment. Ten days after the IM treatment, resting and peak pressures were significantly increased in the injured groups compared to the control group that received no treatment. At five weeks, the anal pressures of the two groups of injured rats receiving treatments were almost on par with the non-injured group.

“Both IM and IV MSC treatment after injury cause increase in anal pressures sustained at five weeks even though fewer cells were injected IM,” Dr. Zutshi concluded. “The MSC-treated groups showed less scarring than PBS treatment, with the IV infusion group showing the least scarring.

“Since MSC delivered IM or IV both resulted in functional recovery, the IM route may be preferable as fewer cells seem to be needed.”

This research demonstrates the regenerative effects of mesenchymal stem cells on the injured anal sphincter. Since fewer cells were needed for intramuscular injections, this mode of administration might be used in future clinical trials, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

Nonhematopoietic Stem Cells from Umbilical Cord Blood Improve Heart Function After a Heart Attack

Xin Yu, who has dual appointments at Case Western Reserve University, in Cleveland, Ohio and the University of Minnesota Medical School in Minneapolis, Minnesota, has published a remarkable paper in the journal Cell Transplantation that describes the use of a stem cell population from umbilical cord blood to treat mice that had suffered heart attacks. The non-invasive way in which these cells were administered and the tremendous healing qualities of these cells makes paper unique.

In 2005, Water Low at the University of Minnesota Medical School described the isolation and characterization of a unique stem cell population from umbilical cord blood that he called nonhematopoietic umbilical cord blood stem cells or nh-UCBSCs. These cells were used to treat animals with strokes and they induced the growth of new brain cells in the brains of treated mice (see J Xiao, Z Nan, Y Motooka, and WC Low, Stem Cells Dev. 2005 Dec;14(6):722-33).

Yu used these cells to treat male Lewis rats that had suffered heart attacks. In all cases, the rats were subjected to open-heart surgery and the left anterior descending artery was tied off to induce a heart attack. One group of rats were operated on but no heart attacks were induced. A second group was given heart attacks, and then two days later were given intravenous saline infusions. The third group was given a heart attack and then two days later, were injected with one million nonhematopoietic umbilical cord stem cells into their tail veins.

Ten months after the surgery, the heart structure and function of animals from all three groups was assessed with tensor diffusion magnetic imaging, and a pressure‐volume conductance catheter. The hearts were also extirpated from the animals and structurally assessed by means of staining and 3-D imaging.

The stem cell-treated animals were compared with the sham-operated animals and the saline-treated animals. In almost all categories, the stem cell-treated animals had better function. Also, the overall structure of the heart was preserved and looked more like the normal heart than the saline-treated hearts. For example, in the saline-treated group, the heart wall thickness in the infarct zone was reduced by 50% compared to the control rats, and wall thickness at the border zone was also significantly
decreased. However, there were no statistical difference in wall thickness between the stem cell-treated group and the control group.

Additional finds were that the stem cell-treated group had significantly smaller areas of dead cells, more blood vessels, and better heart muscle fiber structure that contracted better.

These data show that the long-term effects of nh-UCBSC administration was to preserve the structure, and, consequently, the function of the heart after a heart attack.

However, the added bonus to this work is that the animals were injected with these cells into the tail vein. The animals did not have to have their chests cracked, or have over-the-wire stent technology to implant these cells; they merely introduced them intravenously. Apparently, the nh-UCBSCs homed to the damaged heart and mediated its healing. If such healing can be translated to human patients, this could truly be a revolutionary find.