STEM CELLS

1) Dr. Tarcisio Barros et al (Sao Paulo, Brazil) have infused bone-marrow-derived stem cells into the spinal artery closest to the injury site in 32 subjects with clinically complete injuries (2-12 years post injury). The stems cells were isolated from the patient’s own blood after treatment with a drug that stimulates the bone-marrow production of these cells and, in turn, their spillover into the blood. After one-year follow-up, 18 patients have shown improvement in electrophysiological neuronal conduction, which, in some cases, has been translated into functional improvement. (Photo: Drs. Erika & Tarcisio Barros).

2) Dr. Andrey Bryukhovetskiy (Moscow, Russia), former director of the Russian Navy’s Neurology Department, has transplanted both embryonic/fetal stem cells and autologous (i.e., from the patient) adult stem cells into patients with chronic SCI. In addition in some patients, Bryukhovetskiy has transplanted autologous olfactory ensheathing cells (OECs) using procedures developed by England’s Dr. Geoffrey Raisman. Although not technically stem cells, as discussed above, OECs have considerable regeneration potential and have been the focus of much attention in the SCI research community.

Bryukhovetsiy no longer uses embryonic/fetal stem cells due to the ethical controversy surrounding their use, their rejection potential, and, most importantly, his belief that autologous, adult stem cells are more effective.

Basically, Bryukhovetskiy's transplantation procedures can be categorized as follows:

Embryonic Cells: In 1996, the Russian Health Ministry authorized Bryukhovetskiy to carry out limited clinical trials in SCI. In these early trials, stem cells, neurons, and glia obtained from a various tissues, including 12-week-old human fetuses, were transplanted into the spinal cord/fluid of 17 patients with SCI. Their ages ranged from 16-52 (average 30) years, and the time interval between injury and transplantation ranged from 1-20 (average 5) years. Six, ten, and one had cervical, thoracic, and lumbar injuries respectively. In addition to cell transplantation, all had a variety of other procedures performed depending upon their unique injuries.

Before treatment, 14 subjects were ASIA grade A and three were grade B. After transplantation (0.5 - 3-year follow-up period), four were grade A, five grade B, and seven grade C. Fifteen had some sensory improvement, seven had motor improvement, and 12 had improved bladder function.

SpheroGel & Autologous Cells: Bryukhovetskiy’s team has implanted SpheroGel (a biodegradable polymer matrix) with embedded cells in six patients who required reconstructive surgeries. In three, hematopoietic stem cells were embedded, and, in the three others, olfactory cells. At follow-up (3-8 months), two grade-A patients had improved to grade C, and one had advanced to grade B. In one patient (grade B initially), there was no improvement.

Intrathecal Stem-Cell Transfusion: The intrathecal transfusion of autologous hematopoietic stem cells is the procedure most currently used. Basically, in this relatively straight-forward procedure involving no surgery, the patient’s stem cells are collected without anesthesia and stored with viability until they are transfused back into the patient.

To stimulate hematopoietic stem-cell production and, in turn, cell accumulation in the blood, patients typically received eight subcutaneous injections over four days of granulocytic colony-stimulating factor, a drug also called Neupogen^® or Filgrastim. On day five, the patient is hooked up to a blood separator. Over 3-4 hours, blood is drawn from a vein, processed by the separator, which isolates the stems cells, and returned through another vein.

The collected stem cells are concentrated by centrifugation and slowly frozen in liquid nitrogen (-170^o centigrade) in the presence of dimethyl sulfoxide (DMSO), a cryopreservative that allows cells to be frozen with minimal damage. Care is taken to check for infections so that they will not be later introduced behind the protective blood-brain barrier during transfusion.

At the time of transfusion, the stem-cell suspension is thawed and about 5.3-million cells injected intrathecally into the subarachnoid space (i.e., into the spinal fluid) through a L3-L4 lumbar puncture using a local anesthetic (photo). The procedure, which I observed, is quick and straightforward. The patient can repeat the transfusion in two months. Bryukhovetskiy believes multiple transfusions enhance functional recovery.

In contrast to hematopoietic stem cells, positive results have been limited with the intrathecal transfusion of olfactory cells, previously isolated and cultured from the patient’s nasal tissue.

Although Bryukhovetskiy’s team has collected stem cells from about 120 patients, for a variety of reasons, including the presence of latent infections, only about 60 have had cells reintroduced. Of these 60, 18 have had the recommended multiple transfusions. In turn, 61% of the 18 showed some functional recovery, in some cases dramatic.

Because most patients’ transfusions were relatively recent at the time of this report, it is too early to assess long-term benefit. Early improvements are unlikely caused by comparatively slow neuronal regeneration or remyelination processes and are probably triggered by altering the injury site’s environment through the secretion of growth factors and other molecules.

Bryukhovetskiy hypothesizes that the stem-cells’ regenerative effects are mediated through an important growth factor called ciliary neurotrophic factor (CNTF) and its interaction with a key transmembrane receptor called gp130. This interaction, in turn, influences cell differentiation.

3) Dr. Samuil Rabinovich and colleagues (Novosibirsk, Russia) have transplanted various combinations of fetal OECs, cells from nervous and hematopoietic tissues, and spinal cord fragments into the injury site of 15 patients (Biomed Pharmacother 57(9), 2003). Ranging in age from 18 to 52, patients were one-month to six-years post injury and had complete, Frankel grade-A injuries (Frankel classification evolved into today’s ASIA scale). Each patient received one to four cell transplantations at various times, and was followed at least 1.5 years. Improvements were noted in 11 of 15 patients. Six improved to grade-C, incomplete level, and five were able to walk with crutches. In general, patients who had the transplantations sooner after injury accrued the most benefit.

According to an updating report posted on the investigators’ website www.transplantation.ru (visited September 2, 2005), 102 patients have been treated with a procedure in which the injury site is filled with a gel containing fetal stem cells. The initial transplantation is followed later by one or more additional transplantations of the cells underneath the spinal-cord membrane (i.e., subarachnoid). The time between injury and surgical transplantation ranged from several months to five years. The outcomes for 56 patients who have been followed for at least two years are reported in the table below. As can be seen, at least two years after treatment, only 18% of the patients remained in the most severe injury category compared to 75% before treatment. Investigators believe that since post-treatment improvements accrue gradually, these statistics will continue to improve over time. However, it should be noted that a significant number of patients were treated in a period after injury in which additional function - without any intervention - is often common.

Neurological status in terms of Frankel definition	Number (%) of patients
Neurological status in terms of Frankel definition	before treatment	after treatment
A	42 (75%)	10 (18%)
B	14 (25%)	29 (52%)
C	0 (0%)	12 (22%)
D	0 (0%)	5 (8%)

4) Dr. K-S Kang et al. (Seoul, South Korea) injected stems cells isolated from umbilical cord blood (UCB) into the injury area of a 37-year old woman who had sustained a T-10 complete injury 19 years earlier from a fall (Cytotherapy, 7(4), 2005). Unlike their embryonic counterparts, umbilical stem cells are not controversial. They also have less rejection potential than most other allogeneic donor tissue except embryonic tissue; i.e., some, but not strict, matching between donor and recipient is needed.

In this case, human UCB was obtained from the Seoul Cord Blood Bank, and the UCB cells isolated within 24 hours and, in turn, cultured in media. The investigators indicated that when grown in a neurogenic medium, the cells demonstrated features characteristic of neurons and neuronal support cells (i.e., glia).

With this patient, after a laminectomy, one milliliter containing one-million cells was injected “into the subarachinoid space of the most distal part of the normal spinal cord.” An additional one million stem cells were injected “diffusely into the intradural and extradural space of the injured cord.”

The investigators reported that the patient regained additional lower-limb function within 41 days of the transplantation, including, according to other press reports, some walker-assisted ambulatory ability. Various electrophysiological measurements supported these observations. The investigators suspected that injecting the cells directly into the spinal cord is more effective than infusing them into the fluid surrounding the cord. They do not exclude the possibility that functional improvement was due to laminectomy-related, spinal-cord decompression.

Unfortunately, according to more recent press reports, after her a second stem-cell treatment, her condition greatly deteriorated. She is now unable to sit erect for long time periods and spends most of her day in bed. According to her, “the improvements disappeared quickly. I underwent another treatment, and this is the result. I was unable to move and suffered from extreme pain.”

Doctors suggested she contracted an infection the second time due to either procedural aspects or bacterial contamination of the transplanted cells. As a result, the surrounding tissues have hardened.

5) Dr. Yoon Ha et al (South Korea) has transplanted bone-marrow cells (BMCs) into the injury site of patients with acute SCI (7-14 days post injury) in conjunction with granulocyte macrophage-colony stimulating factor (GMCSF), a factor that stimulates stem-cell production. The bone-marrow cells were aspirated from the patients’ iliac (i.e., hip) bone and further processed. Because these autologous cells are isolated from the patient, there is no rejection potential. After a laminectomy from one vertebra above to one below the contusion site, a total of 1.8 milliliters of bone-marrow cell paste were injected into six points near the injury site.

All patients were men, ranging in age from 17 to 51 years. Five and one had cervical and thoracic injuries, respectively, and all had ASIA-A complete injuries. Five received both bone-marrow cells and GMCSF, and one received only GMCSF.

GMCSF was subcutaneously injected for first five days of each month over five months. In addition to stimulating bone-marrow stem-cell proliferation, animal models suggest that it may also 1) activate macrophages (immune cells) to remove myelin debris that inhibit axonal regeneration, and 2) inhibit post-injury cell death through a process called apoptosis.

Although sensory improvements were noticed immediately after the procedure, sacral-region sensory recovery and significant motor improvements were observed three weeks to seven months afterwards. Four patients, including the one that received only GMCSF, improved from ASIA-A complete to ASIA-C incomplete injuries, one from ASIA-A to B, and one remained at ASIA-A. MRI assessments 4-6 months after injury showed slight enhancement.

Other than GMCSF-associated fever, the investigators concluded that this BMC-transplantation procedure has no serious complications, the study’s goal. Because this intervention and follow-up assessments were performed during a period relatively soon after injury in which some functional improvement is not uncommon, the investigators were careful to avoid conclusions concerning overall efficacy; however, they did quote studies indicating that only a relatively small number (~6%) of patients improve from ASIA-A complete to ASIA-B incomplete injuries.

6) Dr. Eva Sykova and colleagues (Prague, Czech Republic) have implanted autologous, bone-marrow stem cells harvested from the iliac bone (i.e., hip) into 20 patients (Cell Mol Neurobiol, April 22, 2006). Eight were subacute, receiving treatment within 10-33 days of injury; and 12 were defined as chronic, receiving treatment 2-18 months after injury. Soon after harvesting, cells were reintroduced into the patient through the vertebral artery or intravenously. With the subacute patients, four were treated by each route; with the chronic patients, two and 10 received cells via the artery and intravenous route, respectively. Patients were assessed periodically by various electrophysiological measurements and ASIA-impairment scales. Improvements were noted in 1) all subacute patients receiving the cells via the vertebral artery but only one receiving the cells intravenously, and 2) one of the two chronic patients receiving the cells via the vertebral artery. Of the patients who improved their ASIA grades, most advanced from grade A to B, and one from grade B to D (i.e., scale ranging from A, most paralyzed, to E, complete recovery). Although Sykova is cautious in over-interpreting these preliminary results, she believes more benefits accrued when the treatment was done sooner after injury and using the vertebral artery route, which introduces cells closer to the injury site.

7) Dr. Cornelis Kleinbloesem has created a stem-cell oriented company Cells4Health with headquarters in Netherlands but using Turkish surgeons and facilities. The C4H program collects bone-marrow cells from the patient through a puncture in the iliac crest bone (the hip bone) in which a large quantity of bone marrow is concentrated. The isolated stem and other bone-marrow cells are processed through a proprietary process.

The cells are then injected into the patient’s spinal cord at the lesion area through 20-40 microinjections. Cumulatively, about two-milliliters of the stem-cell preparation, corresponding to about 10-20 million cells, are injected above, below, and around the injury site using an insulin needle. In some later cases, cells were also intrathecally (into the spinal canal) or intravenously injected.

At the time of this report, at least 18 patients with SCI have been treated under this C4H program. Of the first nine patients with chronic SCI treated, eight reportedly have had positive results. In three of the first four treated in February, 2005, MRI imaging indicated that the lesion size was reduced by half three months after surgery, data suggesting the creation of new neural cells and supporting structure.

Reportedly, cell transplantation restored some function and sensation in three of these four initial patients. Two to three months after transplantation, the first patient, who sustained a T6-complete injury four years earlier from a car accident, reportedly recovered function to the T12- L1 level and was able to move legs, walk a few steps using a walker, and stand. The second patient, who had sustained a complete cervical-level C5-6 injury seven months earlier, a month and half after surgery was said to be able to move legs and fingers and feel toes, and regained rectal and bladder sensation. Several months after transplantation, the third patient, who sustained a complete C5-6 injury nine months earlier from a surgical complication, reportedly regained his ability to stand, ambulate using a walker with leg braces, and write. Also, his sensation returned to near normal, and he regained rectal control. The fourth patient accrued no benefit, perhaps because his spinal cord turned out to be transected not compressed.

It is important to underscore that many of the results were, in fact, reported by C4H, a for-profit organization, whose continued viability depends upon the generation of positive results. Independent sources have portrayed a less promising picture with many patients not gaining and some even losing function.

More recently, Kleinbloesem has created the XCell-Center located in Cologne, Germany, which appears to carry out many similar stem-cell procedures for a variety of disorders including SCI (http://xcell-center.de/). Specifically, stem-cell-rich bone marrow is obtained from the patient’s hip bone, the stem cells are processed from this marrow, and transplanted back into the patient’s injured cord after exposure by a surgical laminectomy or through a less invasive lumbar puncture into the spinal fluid.

8) Dr. Yongfu Zhang and colleagues (Zhengzhou, China) have transplanted autologous (i.e., isolated from the patient) bone-marrow stem cells into 90 patients with both acute and chronic SCI (1^st International SCI Treatments & Trials Symposium, Hong Kong, December 2005). Of these patients, 10 had cervical injuries, 62 thoracic injuries, and 18 lumbar injuries. The elapsed time from injury ranged from three days to six years. “The injection site was in the upper and lower area between injury and normal spinal cord.”

Thirty-three and 11 patients had improved sensory and muscular ability, respectively after cell transplantation as measured by Frankel assessments (which evolved into today’s ASIA standards). All patients with clinical improvements sustained their injuries within a year of the transplantation procedure. Treatment sooner after injury was associated with better outcomes. The investigators suggested that the bone-marrow stem cells improved blood circulation and inhibited glial scar formation at the injury site.

9) Dr. Venceslav Bussarsky (Sofia, Bulgaria) has treated 12 patients with SCI with autologous stem cells isolated from patient bone marrow from pelvis and chest bones. Only preliminary information was available at the time of this report.

10) Advanced Cell Therapeutics (ACT) According to the company’s website, ACT, registered in the Caribbean Turks and Caicos with connections in South Africa, provides “access to cord blood stem-cell therapy in locations where the treatment is lawful...” According to ACT-generated resources, their cord-blood stem-cell protocols have been used over 700 times for over 80 conditions, including SCI. There has been much adverse publicity concerning ACT operations, and the true nature of the cells.

ACT claimed to have enhanced the therapeutic effectiveness of their stem-cell preparations through a number of procedures. First, white and red blood cells were removed, minimizing rejection potential. Second, key CD133+ stem cells were amplified from the normal 10% of cord-blood stem cells to an elevated 70-80% level. These CD133+ as well as standard CD34+ cells are considered especially powerful stem cells due to their enhanced ability to zero in on a target tissue, differentiation, and engraftment. Third, ACT developed procedures to differentiate cord-blood stem cells into more specialized lines, such as neuronal stem cells for brain and spinal-cord regeneration or pancreatic stem cells for diabetes. Finally, the company supposedly developed freezing techniques that enhanced cell viability after thawing.

ACT reported treating eight patients with chronic SCI with cord-blood stem-cell preparations. Patient age range from 18 to 43; five and three had quadriplegia and paraplegia, respectively; and most injuries were incomplete. About 1.5-million stem cells were introduced into the patient by intravenous and/or subcutaneous injection. After a relatively short follow-up period, most patients reported some functional improvements, including increased sensation, ambulatory ability, and bowel-and-bladder function.

11) Dr. Emilio Jacques (Monterrey, Mexico) has transplanted umbilical cord stem cells into the injury area. Based on limited information, Jacques’ procedures apparently removed the scar tissue by laser, decompressed the spinal cord, injected stem cells into the injury area, and placed patient-derived fatty tissue over the injury area to minimize scar-tissue formation. The procedure is followed by monthly stem-cell injections into surrounding muscles. Sources indicate that Jacques has also started transplanting embryonic stem cells.

One patient who sustained a T5-9 injury about a year and half before treatment briefly described to this report author some of the functional improvement that accrued three months after surgery. Specifically, he feels touch two inches below the T9 level and pressure all the way down to his waist. Furthermore, he can peddle a bike on his own for over 30 minutes, move his hips, push 25 pounds with his legs, and using a harness and treadmill, swing his legs forward.

Jacques’ stem-cell procedures were summarized in a 2005 talk at the 2005 International Congress of Surgeons in Acapulco, Mexico. The submitted abstract indicated that he implanted the undefined stem cells “exactly in the spinal cord injured zone, combined with post-operative use of neuro-muscular rehabilitation, electro-acupuncture, infrared laser, and 4amp drug.”

Of the 59 treated patients (average age 21), 51 and 49% were male and female, respectively; 50 and 9 had incomplete and complete injuries, respectively; and 52, 38, and 10% sustained cervical, thoracic, and lumbar/sacral injuries, respectively. Jacques reported that 68% “gained sensory and motor levels; 16% gained only motor level and the remaining 16% were still the same.” Patients who had sustained lower level injuries, who were younger, and who had less time elapsing since injury did the best.

12) Medra, Inc. under Dr. William Rader’s medical direction, provides a fetal stem-cell program for a wide range of neurological and other disorders, including SCI (see www.medra.com). Although headquartered in Malibu, California, the surgeries are carried out in the Dominican Republic. Very few specifics relevant to SCI-related procedures have been obtained. Derived from elective abortions, fetal hematopoietic stem cells are apparently administered intravenously and fetal neuronal stem cells subcutaneously into the lymph nodes. The program claims that these cells will migrate to the location where they are needed and also release function-restoring growth factors. The program states that the key advantage of using fetal stem cells over, for example, bone-marrow stem cells is that the undifferentiated nature of the former minimizes immunological rejection. This claim, however, ignores the fact that a number of emerging SCI-related stem-cell programs (see above) use autologous stem cells (i.e., isolated from the patient) which are even more immunologically compatible than fetal cells. When contacted several times by the author of this report, the company did not respond.

13) Dr. Geeta Shroff (New Delhi, India) has used human embryonic stem cells (ESC) to treat over 300 patients, including 70 with SCI. Impressive results have accrued, and especially important given the theoretical risks of ESC, no adverse side effects have occurred.

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. Clearly, Shroff’s success was facilitated by her extensive experience working with embryonic cells as a fertility doctor. Her 70% success-rate in making women pregnant through IVF is quite high compared with most other programs. Apparently, the skills she acquired in developing healthy embryos translated well into the creation of robustly therapeutic stem cells. Her cells are prepared with “Good Manufacturing Practice (GMP)” and “Good Laboratory Practice (GLP)” quality-control standards.

Shroff’s key breakthrough is that she has grown ESC without using any animal products, including animal feeder cells often used by other researchers. 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.

Shroff’s ESC 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 many countries, these are insightful guidelines.

Countering criticism she’s using the vulnerable and disadvantaged 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.

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. All patients are carefully followed to document progress.

One of Shroff’s more well-known patients was Ajit Jogi, a 60-year-old Indian parliament member and former chief minister of an Indian state, who sustained a cervical injury from a 2004 auto accident. After injury, Jogi 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.

14) Dr. Satish Totey and colleagues (Bangalore, India) have initiated a pilot study to evaluate the effectiveness of transplanting bone-marrow-derived, mesenchymal stem cells isolated from the patient (i.e., autologous) back into the patient with SCI (www.manipalhospital.org). The cells are extracted from the patient’s hip bone and cultured for several weeks before being transplanted back into the patient. Fifteen individuals with complete (ASIA A), C4-T10 injuries sustained within the previous half year will be recruited into the study. Approximately, one-million stem cells per kilogram of body weight will be injected by relatively non-invasive lumbar puncture (i.e., no laminectomy or opening of the spinal cord membrane) into the spinal-cord fluid (i.e., into the subarachnoid space). To evaluate potential improvements or changes, various electrophysiological, imaging, and clinical assessments will be carried out before and three months after transplantation.

At the time of this report, four subjects had been recruited, of whom one had completed the three-month assessments. This individual, a 32-year-old male, initially received two stem-cell transplantations nearly two weeks apart. In addition to improvements noted by various electrophysiological assessments, the patient reported improved bowel-and-bladder function; increased sensation; improved muscle function and strength, including some ambulation and toe wiggling, and overall enhanced strength.

After completion of this preliminary study, the investigators intend to initiate a more rigorously designed, double-blind-clinical trial.

15)Dr. Robert Trossel (Rotterdam, Netherlands) is reportedly one of the physicians who has treated individuals with SCI with umbilical stem cells provided by ACT. Although available information is scanty at the time of this report, one press report briefly described Trossel’s treatment of a woman with a high-level injury. In this case, 1.5-million stem cells were intravenously injected at the base of her skull where she was injured and at five other locations down each side of her neck.

Trossel’s therapy has generated considerable controversy in The Netherlands for a variety of reasons, including the source and true nature of the implanted cells.

16) Beike Biotechnology Company (Shenzhen, China): Created through funding by or collaborations with several major Chinese medical schools, Beike Biotechnology Company (Shenzhen, China) has treated a variety of neurological disorders, including SCI, with umbilical stem cells (see www.stemcellschina.com). Foreign patients are treated in a hospital located in Shenzhen across the border from Hong Kong. The experience of several patients with incomplete cervical C5-6 injuries has been reported:

In the first case, a 27-year-old male patient from the USA was treated ~2.5 years after injury. Umbilical stem cells together with nerve growth factor were injected above and below the injury site (i.e., surgical implantation) combined with decompression (a potential confounding factor discussed in the “decompression” section). Cells were also intrathecally (into the spinal cord fluid) and intravenously injected into the patient. Since the procedure, the patient has regained additional muscle strength and function in legs and hands, more overall sensation, and enhanced sweating ability, an especially important recovery for him due to living in hot and humid Florida.

The second patient was a 27-year-old Romanian male who was injured ~11 years before treatment in a diving accident. In contrast to the previous case, the patient had the umbilical stem-cell-nerve-growth-factor mixture injected only into the spinal fluid and intravenously (i.e., no surgical implantation). Relatively soon after the procedure, the patient regained new sensation throughout his body, additional strength and movement in hands and legs, stronger abdominal and back muscles, and enhanced bowel and bladder function.

Although it is difficult to draw conclusions with just two anecdotal cases, it has been noted that the second case’s far-less-invasive transplantation procedures produced just as impressive results as the more invasive surgical procedures in the first case.

17) Dr. Gustavo Moviglia et al (Bueno Aires, Argentina) has treated two individuals with bone-marrow-derived mesenchymal stem cells that have been transformed into neural stem cells by culturing with patient-derived autoimmune cells (Cytotherapy 8 2006). Compared to other programs, the science behind this program has an additional, more-difficult-to-understand dimension. Specifically, it combines a stem-cell approach with some of the immunological principles that underlie Dr. Michal Schwartz’ “activated macrophage” program for acute SCI discussed later.

In this program, mesenchymal stem cells were obtained from the marrow of the patient’s iliac crest (i.e., hip) bone, a location where a large quantity of marrow is concentrated. Called the jack-of-all-trades stem cell, mesenchymal stem cells have the potential to differentiate into a wide variety of cell types. After further purification, these stem cells were transformed into neural stem cells by culturing them with autoimmune cells previously isolated from the patient. Because all cells are from the patient (i.e., autologous), there is no rejection potential when implanted back into the patient.

Before stem-cell implantation, the previously isolated autoimmune cells were intravenously infused into the patient. This infusion primes the injury site by generating an inflammation response, creating a more receptive microenvironment for the introduced stem cells. Two days later, the processed mesenchymal/neural stem cells were infused into an artery serving the injury-site area.

The first patient treated was a 19-year-old male who had sustained a thoracic T-8 injury eight months before treatment from a car accident. He received two stem-cell infusions separated by three months. Electrophysiological measurements suggested improved nerve conduction through the injury site, and MRI (magnetic resonance imaging) evaluations indicated increased spinal-cord diameter. After the second treatment, his coordination and walking ability improved. Reportedly, he regained function to the sacral S-1 level.

The second patient was a 21-year-old woman with a cervical C3-5 injury cause by a car accident 30 months before implantation. After one treatment, both electrophysiological and MRI assessments suggested improvements, and the patient regained upper body strength and control, including hand function. Reportedly, she regained function to the thoracic T1-2 level.

Although the regained function reported in these patients is dramatic, experts have questioned the rigor of pre- and post-treatment evaluations that determined the amount of improvement.

18) Dr. R. Ravi Kumar and colleagues (India) have transplanted autologous (i.e., obtained from the patient) stem cells into over 120 patients with SCI (17 & 18). Stem-cell preparation was done in association with the Nichi-In Center for Regenerative Medicine, a Japanese laboratory located in India that specializes in the preparation of autologous - no-rejection - stem cells (19). Stem cells were extracted from 100 ml of bone marrow obtained from the patient. The concentrated preparation, containing about 2-4 million cells, was injected into the lumbar spinal fluid (i.e., intrathecal).

According to presentations at 2007 stem-cell meetings (18), 120 patients who received stem cells in this fashion were followed for six months. Of these patients, 85 were male and 35 female; age ranged from 8-55 years; and time lapsing from injury varied from three months to 11 years. Nine patients had cervical injuries, 38 upper thoracic (T1-T7) injuries, 60 lower thoracic (T7-T12), and 12 lumbar injuries.

Six months after transplantation, 12 and 8 patients improved at least two or one grade(s) of motor power, respectively (greater improvement noted for lower-level injuries); three could walk independently; 14 had sensory improvement or pain reduction; and 18 had improved bladder control. No significant adverse side effects were noted.

19) Reported at the 13^th Annual Meeting of the International Society for Cellular Therapy (June 2007), Dr. Luis Geffner (Ecuador) and colleagues have treated 25 patients with stem cells isolated from the patients’ own bone marrow (i.e., autologous). The time elapsing from injury to treatment ranged from 0.5 months to 22 years (average 4 years). Because considerable functional improvement may accrue without any intervention in the first year post-injury, any improvement of subjects treated soon after injury confounds overall results. Approximately, 1.2-million stem cells per kilogram body weight were implanted, and 4-7 days later, a long-term rehabilitation program was started. Improvement was assessed by a variety of means, including electrophysiological evaluations of nerve conduction, MRI imaging of the spinal cord, urinary function, spasticity, walking ability, and ASIA impairment scales. According to the investigators: “Patients demonstrated improvements in sensitivity, motility, bladder sensation, even controlling sphincters, erection, and ejaculation. Fifteen patients (60%) could stand up, 10 (40%) could walk on the parallels with braces, 7 (28%) could walk without braces, and 4 (16%) could walk with crutches.” Although it is unclear how this data compares to pretreatment function, the ASIA scores improved considerably after the intervention. No adverse effects were observed, and no patient deteriorated due to treatment.

20) Doctors at Tiantan Puhua Hospital, Beijing, China have transplanted bone-marrow-derived stem cells into patients with SCI, five with chronic injuries sustained at least a year before treatment. Because the cells are isolated from the patient’s own bone marrow (i.e.,autologous), they will not be immunologically rejected when transplanted back into the patient. Considering the injury-site “glial” scar as a barrier to regenerating neurons, the doctors ablate (remove) the scar by “medicine” before the cells are transplanted. The cells are grown and amplified in culture for about 3-4 weeks to obtain about 4,000,000 cells, which are then transplanted back into the patient in 3-4 injections spaced two weeks a part. The cells are either implanted into the patient’s spinal cord fluid by lumbar puncture or surgically implanted directly into the injured cord.

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