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Laurance Johnston, Ph.D.

As a part of my research for this column, I’ve traveled the world to check out innovative therapies that have the potential to restore some function after spinal cord injury (SCI). Continuing these efforts, I recently traveled to Delhi, India, where I became the first American scientist to visit a unique SCI stem-cell program.

Developed by Dr. Geeta Shroff, this program has profound implications because it is one of the first to use human embryonic stem cells (ESCs), supposedly the most powerful of all stem cells (see sidebar) with huge therapeutic possibilities. Because much funding is being directed world-wide to tap into these possibilities and potentially enormous profits, the promising breakthroughs of a small Delhi clinic are more likely to be dismissed than embraced by those with conflicting professional and economic interests. However, if we learn from the lessons of history, breakthroughs are frequently generated by innovators outside of the system, who are not shackled by the imprisoning beliefs that often prevail at prestigious biomedical institutions. (Photo: Drs. Ashish Verma, Laurance Johnston, & Geeta Shroff)

Although many issues will need to be addressed before the program obtains widespread acceptance, based on my limited observations, I am excited about its potential and suspect it will ultimately represent a big step toward the promised land of restored function.

Briefly, Shroff has treated over 300 people (70 SCI) with ESCs. Often remarkable results have accrued - and especially important given ESC’s theoretical risks, no adverse side effects have occurred.

A Single Embryo

All cells that have been transplanted into the many patients numerous times were derived from a single, surplus fertilized egg from Shroff’s in-vitro-fertilization (IVF) program. Developed with donor permission, this fertilized egg would have been disposed of under normal circumstances. 

Because Shroff is patenting her procedures, she provided only a generalized description of cell preparation. Clearly, success was facilitated by her extensive experience as a fertility doctor working with embryonic cells. Her 70% success-rate in making women pregnant through IVF is off the charts compared with most other programs. Apparently, the skills she acquired in developing healthy embryos translated well into the creation of robustly therapeutic stem cells. Shroff emphasizes that her cells are prepared with “Good Manufacturing Practice (GMP)” and “Good Laboratory Practice (GLP)” quality-control standards.

Origins and Isolation

Basically, after an egg is fertilized, an embryo is formed, which then splits into a two cells. In Stem Cell Now (2006), author Christopher Scott compares the process to dividing a soap bubble with a knife, creating two smaller bubbles within the confines of the original. Cut again, and it becomes four bubbles or a four-cell embryo. This division goes on, successively creating 8, 16, 32, 64, 128-cell embryo, the total volume changing little.

Between four and six days, the cells rearrange into two layers: an outer layer that will develop into placental and amniotic tissue and a few dozen cells called the inner-cell mass (ICM) which turns into everything else. Now labeled a blastocyst, the embryo is about 0.1-mm across or the size of the period at the end of this sentence.

As the cells continue to develop, they increasingly lose their omnipotent nature. After about two weeks, the ICM starts to organize into three specific layers that become our various tissues: 1) ectodermal layer (developing into nerve, skin, etc), 2) mesodermal (turning into blood, muscle, bone, etc), and 3) endodermal (differentiating into the gut, liver, pancreas, bladder, etc.).

To obtain ESCs, the ICM cells are isolated before they start turning into these layers, and grown in culture. The culturing technology has only recently emerged and requires sophisticated methodology and skill. For example, scientists have had to grow the cells on a layer of animal cells to provide nutrients and the signals needed to keep the cells from further differentiating.

In this regard, Shroff’s breakthrough is that she has grown ESCs without using any animal products, including these feeder cells. By keeping the cells purely “human” in nature, she makes them more amenable to transplantation. The cells from her “mother culture” are further adapted or primed to create daughter cultures targeting specific disorders. Hence, a more specialized cell line will be used to treat individuals with SCI, stroke, diabetes, etc.

According to Shroff, the transplanted cells will home into the tissue where they are needed. Thus, even when introduced by more remote intravenous or intramuscular routes, the cells’ physiological affinity for the target tissue will cause them to migrate where they are needed.

Treatment Exemption

Shroff’s ESCs use is allowed under Indian stem-cell guidelines if the condition or disorder is considered incurable. Given the snail-pace development of real-world stem-cell therapies in the U.S., these are insightful guidelines. Although the U.S.s’ conservative regulatory approach theoretically ensures safety and efficacy, it also creates hard-to-surmount barriers that inhibit the introduction of helpful therapies, especially for a disorder like SCI with a limited economic market.

Pursuant to the guidelines, Shroff’s procedures have been reviewed by an ethics committee that oversees the program. She emphasizes to all prospective patients, who must sign an informed-consent document, that there is no guarantee of success.

The 300 treated patients represent diverse “incurable” disorders. In one of the more dramatic examples of the potential power of these cells, a patient who was in a persistent vegetative state for many years – similar to the well-known Terry Schiavo case in the U.S. - become responsive for the first time after ESC treatment.

Countering criticism she’s using vulnerable and disadvantaged people as guinea pigs, Shroff notes that 30% of her patients are physicians or have family members who are physicians. In other words, highly educated medical professionals who appreciate underlying issues have chosen to avail themselves of the treatment.

In addition, a number of senior government officials have been treated and, based on their comments to me, are delighted with the benefits. Documenting interest in her program at the highest levels, Shroff has briefed the Indian President and Prime Minister. Finally, showing that her program is more than just a profit-making venture, many of her indigent patients have been treated without charge.


As I traveled through 13 time zones, it took nearly two days to travel to Delhi, and jetlag’s impact was severe on sleep and my daytime mental acuity. Because the monsoon rains had not started, temperatures exceeded 110o F in the dusty city. Hardly noticed by the locals, the ubiquitous din of horn honking didn’t fade until the middle of the night. Many spoke fluent English. As in many countries I have visited, a McDonalds was nearby - although perhaps unique in the world of McDonald’s, no beef was served. 

Shroff’s Nu Tech Mediworld clinic is located next to Father Agnel Catholic School, and uniformed students often enthusiastically played in the park in front of the clinic. Although most patients are treated on an outpatient basis, the clinic is a 20-bed small hospital where they can stay if required. It includes a modest physical-rehabilitation area with therapists motivating patients to new levels of achievement. This area was a congregating point for sharing good news and positive developments between patients and family members.

Overall, I was impressed with the optimistic outlook that pervaded the clinic. In addition to patient optimism, staff at all levels, from the doorman to physicians, projected an attitude that they were part of something special that was helping their fellow man and truly making a difference. Shroff and her collaborating physician Dr. Ashish Verma have an informal, open-door policy in which patients drop in and provide progress updates.  

Treating SCI

Due to a booming economy, India has a burgeoning SCI population. Because of the societal impact of so much SCI, policymakers believe new approaches - such as Shroff’s stem-cell program - are desperately needed.

Shroff has treated about 70 persons with SCI. Although she believes that treatment would be optimal when started close to injury, most of her patients have been injured for at least a year. Basically, she decided not to treat the more acutely injured patients because critics would dismiss improvements as something that would have occurred anyway during a period in which functional gain is not uncommon.

Patients often visit the clinic several times for a series of transplantations. The cells are introduced through a variety of routes, including intravenous or intramuscularly injections, and more infrequent intrathecal transplantations directly into the spinal-cord region. The number of transplanted cells increases over time.

During my visit, I interacted with many of Shroff’s patients, including:

Ajit Jogi (photo), a 60-year-old Indian parliament member and former chief minister of an Indian state, sustained a cervical injury from a 2004 auto accident. He was unable to sit up and had difficulty breathing and even writing. Since treatment, he can walk about 10 steps with braces, has regained significant bowel and bladder function, has full sensation down to his toes, and, with the renewed, very-evident energy has resumed a politician’s busy life style.

Sonja Smith, a 45-year-old mother from Brisbane, Australia, sustained a thoracic T11-12 injury 18 months earlier when she attempted to stop her car from rolling down a hill with her three young daughters inside (photo: Smith with mother & sister). After two months of transplantations and physical therapy, she has regained sensation and strength in her legs and feet, can walk with the assistance of braces and a walker, and has regained some bowel and bladder control.

Several years ago, Dr. Nalin Bhatia (photo with wife), an Indian military physician, acquired a T4-6 injury after his car went off a cliff, an injury aggravated by rescue workers crudely hauling him up the cliff with ropes.  Although Bhatia has focused his ESC-treatment on healing a bad pressure sore and regaining bladder control, he is now able to walk with some support and has increased muscle strength.

Other patients less fluent in English included a jockey, injured when his horse rolled over him; a math teacher who fell off his house roof; and a salesman who acquired tubercular paraplegia. They all stressed that they have regained substantial, life-enhancing function of some sort since initiating treatment. In addition, the salesman highlighted an often expressed, but more intangible, outcome. Specifically, his most important benefit was a renewed, life-force energy that coursed through him once again, a force which manifested in his everyday outlook and activities.

All patients are carefully followed to document progress.


Although many SCI stem-cell programs are emerging, Shroff’s approach is unique because it transplants ESCs, a procedure only in the planning stages in the U.S. Being the “mother of all stem cells,” ESC have great potential to differentiate into therapeutically useful tissue. The concern that they could turn into something bad has not been realized so far in Shroff’s program. Nevertheless, people considering any stem-cell procedure should carefully weigh, relative to their unique situation, potential benefits that may or may not accrue against undefined risks.


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 (CNS) develops, ESCs evolve into more specialized adult neural stem cells, which eventually turn into neurons and related tissue.

Omnipotent ESC have the greatest potential to differentiate into a wide range of cell types, although scientists 1) have had difficulty steering them in the desired direction and 2) are concerned that they could turn into something undesirable (e.g., tumors, etc). Adult stem cells are found in most tissues, including the CNS. Generally, they differentiate into the specialized cells connected with the originating tissue; however, when certain cues are provided, they can transform into cells associated with other tissue. For example, under appropriate circumstances, bone-marrow-derived stem cells can differentiate into nerve cells and, indeed, are being used in several SCI-transplantation programs.

When adult stem cells are obtained from the patient, there is no immunological rejection when they are transplanted back into the person. Supposedly, this is the case also when ESC are transplanted because these cells have yet to develop an immunological signature that’s viewed as foreign.

However, as the embryo develops into a fetus (~8-12 weeks), the cells have matured sufficiently to develop such a signature, and, in turn, possess more rejection potential. Hence, ESCs seem to be ideal transplantation candidates because they combine maximum potential to morph into therapeutically useful tissue with minimal rejection potential.


Adapted from article appearing in August 2007 Paraplegia News (For subscriptions, call 602-224-0500) or go to www.pn-magazine.com