As discussed elsewhere, experts believe that stem cells have considerable potential to restore some function lost by disability, disease, or the entropy of aging.

In brief review, stem cells are progenitor cells that have the potential to transform into a wide variety of tissue. Although often dichotomously categorized as either embryonic or adult, they actually represent a continuum of cell types that differentiate into our end-product tissue. For example, as our central nervous system develops, human embryonic stem cells (hESC’s) evolve into more specialized adult neural stem cells, which eventually turn into neurons and neuronal support cells.

When adult stem cells are isolated from the patient, there is no immunological rejection when they are transplanted back into the same individual. This also seems to be the case when hESC’s are transplanted into patients because these immature cells have yet to develop an immunological signature that’s viewed as foreign.

In other articles, I’ve discussed various stem-cell programs emerging throughout the world, including a promising one I visited in New Delhi, India in 2007. Developed by Dr. Geeta Shroff, this program was one of the first to use hESC’s in an effort to restore some function after spinal cord injury (SCI). Since my visit, she has collected a vast amount of data on the patients she has cumulatively treated over time with her hESC preparations. This update specifically summarizes the results of treating 226 individuals with SCI.

HESC Preparations
All of Shroff’s hESC preparations were derived from an extra, fertilized ovum harvested with donor permission as part of an in-vitro-fertilization process. Approximately, 24-48 hours after fertilization, the 4-16 cell ovum was suspended in media and grown in culture. The cells from this “mother culture” were further adapted or primed to create daughter cultures targeting specific disorders, such as SCI. Unlike many scientists who have attempted to culture such cells, Shroff has managed to grow her cells without using any animal-derived products or media. By keeping the cells purely “human” in nature, they become more amenable to transplantation.

Studies suggest that various molecular factors released by the injury site attract the transplanted stem cells. Thus, Shroff believes that the transplanted cells can home into the areas where they are needed. Hence, even when the cells are introduced by more remote intravenous or intramuscular routes, their physiological affinity for the target tissue will cause them to migrate where they are needed.

ASIA-Impairment Scale
To assess patient improvement after treatment, Shroff used the commonly administered ASIA-impairment scale. Basically, the scale describes the degree of injury incompleteness, grading injuries on a scale ranging from A to E. “A” corresponds to a complete injury, “B” a sensory-incomplete injury, “C” a motor-incomplete injury, “D” a motor-incomplete injury with more recovery, and “E” motor and sensory recovery.

Patients
Over a seven-year period starting in 2005, Shroff transplanted her hESC preparations into 226 individuals with SCI sustained at least three months before treatment (i.e., those with more acute injuries were excluded). Of these patients, 90 and 136 had quadriplegia and paraplegia, respectively; age averaged 28 years (range 20-34); and 74% were males.

Treatment
Shroff’s study consisted of three treatment phases with a 4-8-month gap between each phase. These gaps permitted the transplanted hESC’s to grow and differentiate, hopefully, allowing the creation of some function-restoring regeneration. In the first phase (eight weeks for paraplegia and 12 weeks for quadriplegia), hESC’s were administered intramuscularly twice daily, intravenously every 10 days, and by various supplemental routes every 5-7 days to introduce the cells closer to the injury site. The second and third phase consisted of 4-6 weeks of similar treatment. To maximize any restored function, all patients received physical therapy.

Results
At the end of the first treatment phase, 45% of the 226 patients improved at least one grade on the ASIA-impairment scale. Of the 153 patients with ASIA-A complete injuries at the start of phase one, 80 improved to either ASIA-B or -C incomplete level. Additional improvements were noted for patients who continued treatment through phase 2 and 3. Overall, by the end of phase three, 70% of the patients had improved by at least one grade on the ASIA scale.

Various radiological imaging techniques (e.g., MRI and tractography) confirmed these improvements. Correlated with these results, Shroff observed improvements in voluntary movements below the level of injury, bladder and bowel sensation/control, gait, and hand grip.

Other than fever and headaches, no significant side effects were observed from treatment. No difference in response was noted between men and women.

Conclusion
Although recognizing the limitations of her study and hesitant to over-extrapolate results, Shroff believes her results are strongly encouraging, stating “hESC transplantation in patients with SCI is safe and effective and helps improve the clinical condition of patients.”

 Overall, Shroff’s pioneering work undertaken in a small Indian clinic is an impressive contribution, worthy of open-minded consideration by the SCI scientific establishment. However, in spite of its promise, people considering her (or any) stem-cell program, should have realistic expectations, recognizing that any functional return may be modest at best.

Contact: Dr. Geeta Shroff’s Nutech Mediworld Clinic is located in New Delhi, India, phone 91 11 26565548; email geetashroff@hotmail.com.
 

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