Rolling Feature ? Stem Cell Therapy: In search of a cure
This question has become very relevant in the last couple of months. During November last year the Southern African Spinal Cord Association (SASCA) hosted its biennial congress in Cape Town. One of the key note speakers at this conference was Dr Brian Kwon from Canada. He is one of the leading experts and most widely published authors in the field of Translational Research. This entails the field of study that seeks to translate success stories in the laboratory to clinical, practical and useful therapeutic interventions.
A second important event took place during the early part of December 2012. A procedure was performed by a leading Neuro-Surgeon in a private clinic in Cape Town, where the injured spinal cord of a chronically injured patient was resected and the defect was bridged with a form of stem cell therapy. This was done in the hope of curing the patient's paralysis. These two important events leads us to the question: "Where are we in finding the cure for spinal cord injury (SCI)?
To answer the above question adequately we first have to look at what has been done in the past: To this end an article was published in Spinal Cord (2013) 5: 2-9 entitled." Clinical trials in spinal cord injury : lessons learned on the path to translation, the 2011 International Spinal Cord, Ludwig Guttman memorial lecture.
This was authored by Prof. D P Lammertse who has been attached to the Graig Hospital in Denver for many years and is probably one of the leading researchers working in this field. This lecture was given at the last meeting of the International Spinal Cord Society (ISCOS) in London. In the article he deals at length with all the most important clinical trials that were conducted in the last thirty years. These start off with the controversies regarding the use of steroids in SCI; continues with the more advanced drug studies such as the Syngen study of the 1990's; and even deals with treatments such as structured rehabilitation programmes.
A number of lessons learned were summarised namely: "The control of bias- trial design is important. All of us are biased when we judge information regarding a possible cure for SCI. This is true of clinical research patients, people living with SCI for many years etc. The only way to control this is to have properly designed prospective randomised control group designed studies. In other words studies need to be designed so that bias is excluded to the highest degree possible. "Confirmatory evidence is the key. Significant results in a single trial are not sufficient to establish a standard of cure. Therefore, to work in isolation without repeating studies at multiple sites does not benefit the community at large." The primary outcome measurement choices are critical. We need to be able to accurately measure improvement or the lack of improvement in evaluating a treatment modality. We all know that virtually no two people with a SCI have exactly the same neurological picture. Within a similar group of injuries there is variation in levels of sensation sparing, spasticity patterns etc. Even in one individual this curves over times. Therefore, we have standard reporting measures to compare apples with apples. "Key outcome examiners should be trained on these outcome measures. It is of no use that I report on my results in a treatment that I believe in. My results should be tested by trained individual researchers, who are familiar with the outcome measures selected. These are some of the key parts to remember when evaluating any new form of treatment. This brings us to the next question: What about Stem cells?" Stem cells have been the subject of extraordinary high expectations, founded more on media hype than scientific data parts. However, they do remain among the most versatile and promising potential therapies for SCI.
What are stem cells?
Stem cells are cells that are able to renew themselves by cell division and in so doing, they can differentiate into different cell types. Two main types of stem cells are available, namely embryonic stem cells and adult stem cells. Now, embryonic stem cells are only found from the inner cell mass of the blastosyst, which is a very early stage of development of the human embryo. There are huge ethical and moral issues in using these stem cells for research and, or treatments as the only source of these stem cells are the fertilised embryo's held in fertility centres, or, secondary of your own cord blood saved at birth. The allure of these cells are that they are pleuri-potentic, meaning they can differentiate into virtually any cells, provided that they are guided by the right environmental factors. Therefore, we can literally grow new nerve cells that are exactly the same as the injured cells in the spinal cord and thus, hopefully cure diseases.
This has applications throughout medicine not only in spinal cord injuries.
The second major source of stem cells is adult stem cells. These cells are found in adult tissues. They are at best multi-potentic, which means that blood stem cells can divide into blood cells, nervous tissue into nerve cells, etc. They are therefore further along the line of differentiation, but have less bothersome ethical and moral issues in research.
What studies have been done in the field of cell based therapies? Numerous laboratory and early clinical studies are being performed.
The following are a quick overview of the different studies:
I. Schwann cells: Schwann cells are the myelin forming cells of the peripheral nervous system. Their ability to form cellular bands and to support axonal nerve re-growth after injury was recognised almost a century ago. Pros of Schwamm cells are:
- Extensively studied and shown to guide cescens and provide neuro-protection;
- Can be harvested from the patient for autologious transplant (self-transplant). Cons of Schwann cells are:
- Requires adjuvant or added treatment to convey efficacy;
- Limited integration into the host compare to neural stem cells;
- Optimal source of Schwann cells yet to be determined. II. Olfactory Ensheating Cells (OEC's):
- These cells are found at the base of the skull and at the top of the nose, and are of interest because they are the only nerve cells that continue to grow life-long.
Pros of OEC are:
- Good integration into host spinal cord;
- Behavioural improvements in the experimental animals have been reported by multiple studies;
- Offer the possibility of autogenous transplant. (Self-harvest) Cons of OEC are:
- In thoracic injury, model results are not promising;
- Human protocols for OEC still need refinement;
- Most cases need co-treatment to increase efficacy. III. Neural Stem / Progender cells (NSPC) :
- These are true stem cells harvested in laboratory rat embryos from certain parts of the brain.
Pros of NSPC are:
- Show good integration into the host spinal cord;
- Can differentiate into nerve cells and supporting structural cells;
- Most studies do show improvements in fractures in laboratory animals. Cons of NSPC are:
- They do not provide optimal bridges for axonal re-growth;
- Sourcing of these cells are problematic;
- There is the possibility of tumours forming and we do not necessarily how to switch these cells off. IV. Bone marrow derived stem cells (BMSC):
- Blood cells are harvested from the bone marrow and then taken back along the path of differentiation.
Pros of BMSC are:
- Easily harvested;
- Proven to be effective in laboratory SCI models;
- Large animal and primate studies have been successful. Cons of BMSC are: â€¢ Integration into the spinal cord has been problematic;
- Differentiation and quality of cells are difficult to predict. Are cell based therapies the only therapies that are being investigated?
"No definitely not," according to Dr Brian Kwon and Prof. Michael Fehlings in their book NAME OF BOOK on translational issues, the breakthrough in the last twenty years can be summarised as follows:
- There have been at least ten major breakthroughs that can be grouped into four major groups.
- Stem Cells Neuro restoration: â†’ Plasticity enhancement
- Axonal regeneration: (making new nerves) (nerve cells performance
- Repair of injured site. different function) â†’ Neuro Modulation â†’ ABRT:
- (Activity based rehab therapies,
- here are things such as
- FES / locomut /
- weight bearing etc.) Medical Management: Surgical Management:
- Blood pressure management; Early decompression possibly advantageous.
- Neuroprotective agents ie.
- Steroids, management of chronic
- problems. Where does this leave me as an individual living with a SCI?
- There is going to be a cure for spinal cord injury but it is unlikely to be a single bullet type of approach where one drug or therapy is going to be the be-all and end-all of therapy. This is very similar to other chronic conditions in medicine i.e. hypertension, diabetes or heart disease. There is no single pill or operation that cures any of these either.
What should I know when I am considering going for stem cell therapies or what should I do when confronted by articles in newspapers that claim to have found the cure?
In a letter to the editor of the Spinal Cord Journal (2209) 47: 773 - 780, Blight and a group of the world's leading minds on spinal cord injuries had the following statement:
"We do not rule out the possibility that cell based therapies may improve function and quality of life for recipients and justify the risks, but insist that the onus is on the providers to deliver such proof from a valid clinical trial program. It is unethical to sell unproven therapies, we do not advise patients to volunteer for such treatment procedures. Unfortunately, in the context of an entrepreneurial enterprise, it is unlikely that accurate, reliable or useful medical evidence will ever be generated."
This is the official position of SASCA and we encourage all health care practitioners to form part of our search for a cure.