Cell Transplantation Sought After in the Age of Medical Tourism

By Edelle Field-Fote, PT, Ph.D.
Director of Spinal Cord Injury Research, Shepherd Center

With the many hundreds of medical and scientific journals publishing new articles all the time, it is often interesting to see which of these gets coverage in the mainstream media.  Such was the case with a recent report of the development of pain due to a spinal mass in a woman who had received a transplantation of cells into her spinal canal (Dlouhy and colleagues, 2014). 

The report, published in the Journal of Neurosurgery: Spine (and available online by clicking here) details the unexpected outcome of a mucosal cell autograft. In the procedure, which the woman had undergone eight years prior, cells from the olfactory (nasal) mucosa (which lines the lower nasal cavity) were transplanted into her spinal canal at the level of injury. The goal of the procedure was to achieve some restoration of motor and/or sensory function by encouraging the growth of beneficial olfactory ensheathing cells and progenitor cells that comprise the olfactory mucosa. 

However, in addition to these target cells, the olfactory mucosa may also contain other types of cells, such as respiratory mucosal cells whose function is to produce mucus. In this case, it appears that the latter cells made up most of the mass that developed in the woman’s spinal canal. The growth of the mass compressed the spinal cord, resulting in the pain that caused her to seek medical care.

While there are as yet few objective reports of significant improvements in motor and/or sensory due to neural transplant procedures applied on a large scale, the reports of significant adverse effects such as those detailed in this case report are also rare. In an age of “medical tourism” where consumers seeking health benefits have the opportunity to travel to countries with varying standards of consumer protection, this case report brings to light some important issues that warrant consideration. Perhaps the most important issues to be considered are:

1) the need for consumers to be fully aware of the details of the procedures they are considering, and;

2) the need to be aware of the distinction between a genuine clinical trial and a fee-for-service intervention that is experimental.

Above all, do no harm.

The oath “above all, do no harm” is the foundation of healthcare practice and underlies the compelling requirement for “safety first” in the application of potential interventions.  Before the question of efficacy of a possible intervention is even considered, the procedure must have been shown to be safe. Typically, in the United States at least, safety must have first been demonstrated in preclinical studies using an animal model that is relevant to the intended human application. 

For example, studies of animals with thoracic-level lesions may have limited value for informing procedures that will be used in individuals with cervical spinal cord injuries (SCI). Likewise, as was true in the case report referenced above, some of the complications that could result from an experimental procedure may not be apparent until long after the procedure.

For the informed consumer, the relevant questions are: 

• Does the animal model that was used to test the safety of this intervention have relevance for human spinal cord injury? 
• Was safety assessed for a reasonable amount of time following the procedure?

The devil is in the details.

A recent systematic review that included 10 studies of 1,193 patients with chronic SCI concluded that reasonable evidence exists for the safety of olfactory ensheathing cells in individuals with SCI (Li et al, 2014). However, in those studies for which the best results were obtained, the cells were highly purified and then grown according to the strict guidelines of good manufacturing practices (GMP) to increase the likelihood that only the cells of interest were included in the material to be transplanted into the recipient. 

Based on the outcome of the case reported by Dlouhy and colleagues, it appears that the material transplanted into the recipient included cells other than the olfactory ensheathing cells and progenitor cells. For the informed consumer, the relevant questions are: 

• What cells will be transplanted? 
• Will these be my cells that are harvested and grown, or will the cells come from another source? 
• How will the cells be prepared before they are transplanted? 
• Will the procedures used to prepare the cells meet the standards of GMP facilities?

Check it out.

There are a number of steps that a prospective participant can take to ensure that an experimental intervention is safe as possible and has at least some evidence of its potential efficacy. The first thing that a potential participant will want know is whether the trial being considered has a control group that does not receive the treatment. Whether or not there is a control group usually depends on whether the study is a phase 1, 2 or 3 trial. In clinical trials with a control group, participants are randomly assigned to either a treatment group or a control group so neither the participant nor the investigator knows the group assignment. This approach allows the value of the treatment to be evaluated in an unbiased way. In some trials, participants initially assigned to the control group can receive the treatment later.

A phase 1 trial typically does not have a control group; rather, the study is performed in a small group of participants with the goal of establishing that the treatment is safe for human participants. If found to be safe, then a phase 2 trial is done to establish preliminary evidence that the treatment is associated with positive outcomes. Phase 2 trials typically have a small treatment group and a small control group. If the phase 2 trial shows evidence of efficacy, then the study proceeds to phase 3 and involves larger treatment and control groups. Some questions to ask include:  

• Is it possible that I would be assigned to a control group? 
• If there is a control group, will those initially assigned to the control group be given the opportunity to receive the treatment at a later time?

When considering participation in a clinical trial, as noted above, safety is the first consideration. Assuming there is evidence the study treatment is safe, the participant will want to know what positive benefits might be expected because of participation. It is important to weigh the potential benefits against the possible risks, and this is very much an individual decision. For some people, having a small improvement in sensory function may be sufficient to warrant the risks associated with participation. Others may wish to participate in a trial only if there is evidence of meaningful change in motor function.  However, even “meaningful change” is defined differently by different people, and may depend on the level and severity of injury. 

For example, for someone with tetraplegia anticipating some recovery of arm/hand function, a change of five points on the upper-extremity motor scale may make a meaningful difference to function. While in an individual with paraplegia, the same five-point change in lower-extremity motor function may or may not make a meaningful difference to function. Some questions to ask are: 

• What changes might I expect as a result of participation? 
• How will these changes be measured? 
• What will these changes mean in terms of my real-world function?

Resources for identifying and evaluating available trials

Today, the internet makes it easy to learn about experimental treatments that are available, but it is sometimes difficult to distinguish between legitimate clinical trials and questionable fee-for-service treatments. Perhaps the most important consideration is that legitimate studies never charge participants for the treatment they receive as part of a clinical trial, as it is considered unethical to charge for a treatment of uncertain value.  There are dozens of “treatments” for spinal cord injury being offered via the internet.  Many of these have an associated blog where those who have been through the treatment offer their opinions about the outcomes. However, the majority of these lack objective measures of change that have been evaluated by someone not associated with the person or group offering the treatment.

In the United States and some other countries, legitimate clinical trials must be registered; the most commonly used registry is clinicaltrials.gov. The investigator leading a clinical trial is required to enter the trial into the registry before enrollment begins. A registry allows people who may be interested in participating in a clinical trial to learn about the purpose of a particular trial, who may participate, the length of the study and the schedule of procedures or tests, possible risks and other important information. The study personnel of clinical trials are available to answer questions about the trial, and also can provide contact information of experts not involved in the study who can offer independent advice. 

Along with resources for identifying available clinical trials, the International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) has an excellent guide for evaluating the strengths of these trials (Steeves and colleagues, 2007). The guide provides additional details related to each of the criteria described above, as well as a checklist of questions to ask of the investigators involved in the trial. 

Also, Shepherd Center researchers are available to answer questions about studies you may be considering. For more information, contact Edelle Field-Fote, PT, Ph.D., at Edelle_Field-Fote@Shepherd.org.

For more information on Shepherd Center research, click here.

REFERENCES

Dlouhy BJ, Awe O, Rao RC, Kirby PA, Hitchon PW. Autograft-derived spinal cord mass following olfactory mucosal cell transplantation in a spinal cord injury patient. J Neurosurg Spine. 2014 Jul 8:1-5.

Li L, Adnan H, Xu B, Wang J, Wang C, Li F, Tang K. Effects of transplantation of olfactory ensheathing cells in chronic spinal cord injury: a systematic review and meta-analysis. Eur Spine J. 2014 Jul 8. [Epub ahead of print].

Steeves JD, Fawcett JW,  Tuszynski MH, et al. International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) February 2007.  ISBN 978-0-9782959-0-5. http://icord.org/wp-content/uploads/2012/08/Experimental_treatment_ for_SCI-full-open-revised17Jan08.pdf. Accessed July 14, 2014.

EDELLE FIELD-FOTE, PT, Ph.D., is the director of spinal cord injury research at Shepherd Center. She joined the staff in May 2014 after serving for 20 years as the director of the Neuromotor Rehabilitation Research Laboratory at the Miami Project to Cure Paralysis. Her research focuses on restoring motor function after spinal cord injury by making use of spinal pathways not damaged by injury.