EMBRYONIC STEM-CELL TRANSPLANTATION: NEW BEGINNINGS
Laurance Johnston, Ph.D.
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.
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.
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
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%
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.
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
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
Contact: Dr. Geeta Shroff’s Nutech Mediworld Clinic is located in New
Delhi, India, phone 91 11 26565548; email email@example.com.