Treating spina bifida in utero with stem cells

Dario Fauza, MD

A pilot study led by Dario Fauza, MD, associate in Surgery and of the Advanced Fetal Care Center (AFCC), finds promise in using neural stem cells to help repair spina bifida before birth—augmenting fetal surgery with tissue regeneration techniques. In spina bifida, a congenital defect that emerges around the fourth week of gestation, a portion of the spinal cord and its surrounding structures develop outside the body, causing partial paralysis, urinary and fecal incontinence and musculoskeletal deformities. Fetal surgery to repair spina bifida has been available for a decade, but has led to only limited improvement in spinal cord function. "To date, all that has been attempted is the prevention of further insult to the cord, rather than repairing damage that has already occurred," says Fauza.

Fauza's team modeled spina bifida in fetal lambs—similar in weight and size to a human fetus—splitting the animals into three groups. The first group had no repair, the second received standard surgical repair and the third had surgery plus an infusion of neural stem cells directly into the spinal cord. In this last group, the delivered cells engrafted selectively in the most damaged areas of the spinal cord, remained viable and produced factors that protect nerve cells and encourage nerve growth—the first steps in initiating a repair process. The findings appear in the September issue of the journal Surgery.

"Further studies will look at different forms of neural stem cells and alternative delivery methods," says AFCC Director and study co-author Russell Jennings, MD. "They will also provide longer-term data, giving us a better idea of how successful in utero repair will be in humans."

Disease-specific stem cell lines created

Induced pluripotent stem cells derived from skin cells taken from a patient with Parkinson's disease. (Image: Courtesy Hyun Park, PhD.)

Last December, researchers led by George Daley, MD, PhD, and In-Hyun Park, PhD, of Children's Stem Cell Program, reported converting skin cells from an adult volunteer into cells that look and act like embryonic stem cells. These cells, called induced pluripotent stem cells (iPS), are created through genetic reprogramming and can potentially form any cell type in the body. Now, in collaboration with the Harvard Stem Cell Institute (HSCI), Daley and Park have created iPS cell lines modeling 10 different diseases, allowing researchers to watch the diseases as they unfold in developing tissue and perhaps discover new treatment possibilities.

Daley had long sought cell-based models to better understand human diseases, with his particular interest being blood disorders. The new iPS cells, to be shared freely through a repository housed at the HSCI, include lines with Parkinson's disease, Type I diabetes, Huntington's disease, Down syndrome, a form of combined immunodeficiency ("bubble boy disease"), Lesch-Nyhan syndrome, Gaucher's disease and two forms of muscular dystrophy. "The original embryonic stem cell lines are generic and allow you to ask only basic questions,"Daley told reporters at a press conference in August. "These new lines are just the beginning for studying thousands of diseases in a petri dish."

Described online on August 6 in the journal Cell, the iPS lines were developed from the cells of patients ranging in age from one month to 57 years old. But Daley emphasizes that he's far from ready to abandon experiments with embryonic stem cells. Such research needs to continue in tandem with approaches that reprogram adult cells, he says, to bring cell-based therapies to the clinic as quickly as possible.