The Latest in Stem Cell Therapy Research for Spinal Cord Injury

Apr 12, 2016 | Trends

Spinal Cord Injury/Disease SCI/D (or simply SCI) is defined as damage to any part of the spinal cord or nerves at the end of the spinal canal, the result of which is often permanent changes in the strength, sensation and other functions of the body from below the site of the injury. In 2013, WHO (World Health Organization) reported that as many as 500,000 people worldwide suffer from a spinal cord injury each year. In the US, 250,000 to 450,000 people live with SCI and there are 10,000-12,000 new cases annually. The causes are broad but around 70% of SCIs are caused by either vehicular injury or damage sustained by a fall and most of the rest are caused by violence (mainly gunshots violence) and sports-related injuries (mainly diving). Around 80% of SCI patients are men in their mid-teens to early thirties.

Quick Fact!

The spinal cord is a collection of millions of nerve cells that form a delicate tissue. This is surrounded and protected by vertebrae.

At the moment, post-accident therapies focus on extensive physical therapy, occupational therapy and other types of rehab therapies to help teach the SCI patients to adjust and adapt to their disability. Surgery is used as well as various medications for pain, muscle spasms, muscle spasticity and other SCI-related symptoms. There is no “cure” for SCI in humans, no way to fully regrow and heal the damaged tissue…at least not yet.

The One Size Doesn’t Fit All Problem

Each spinal cord injury is unique but can be grouped and classified based on meeting certain criteria:

  1. Which region of the spine in the injury in: cervical, lumbar and/or thoracic? Which vertebrae within these are injured?
  2. How severe and what is the extent of the injury? This is done on using the ASIA/ISCoS Exam Chart (ASIA Impairment Scale or AIS)
  3. Is the injury complete (meaning no function below the site of injury) or incomplete (meaning partial function still in tact)? If it’s incomplete, where is the damage, the front, back, side, center?
  4. When did the injury occur: is it recent or did it occur a while ago?

Stem Cell Therapy (SCT)

As we saw in a previous article, SCT has given much hope to many areas of medicine. In particular, diseases with inadequate treatment options like MS and SCI are eagerly exploring SCT. There are many possible ways SCT could play a significant role in treating SCI including replacing damaged/dead nerve cells; introducing new myelin-promoting cells to insulate damaged nerves and allow them to conduct signals more effectively; preventing further damage to the site of injury by secreting healing and protective factors; and preventing/reducing further injury by suppressing inflammation at the injury site. The most important aspect of SCT is the prospect for patients of having something that could give them any more function than they currently have, whether it’s the ability to brush their own teeth, use the bathroom unassisted or pick up a loved one’s hand.

When you hear of SCIs, the first question that comes to mind is: why don’t the nerve cells just grow back? When you cut your finger or have a tooth pulled, the tissue heals. Even peripheral neural damage results in regeneration. The answer lies in how the body responds to damage to the spinal cord and brain (collectively called the CNS or Central Nervous System). Normally injury results in a host of repair factors being released and the recruitments of tissue regeneration cells to the site of injury, however in SCI this response is usually turned off. The CNS is an immunosuppressive environment that is designed to minimize inflammation to avoid any damage that a sustained inflammatory response can cause. In SCI, factors that block axon growth flood into the site of SCI resulting in minimal nerve regrowth and recovery. This anti-repair process is really an anti-growth mechanism that under normal circumstances prevents aberrant growth of neurons. Sadly, this same mechanism leads to a severely reduced ability of the CNS to regenerate. The logic here is that it is better to have partial function or even no function below the site of the injury than to die of complications resulting from prolonged inflammation in the CNS.

Nerve cells are terminally differentiated and thus cannot proliferate to fill in any “gaps” caused by injury. The trick to repairing SCI may be to very carefully manipulating the site of injury to encourage healing and this is where stem cells come in.

Opening the Doors to Human Studies

In SCI, the first SCT trial took place in 2010 (the “Geron Study“) and used a very low dose of human embryonic stem cell-derived oligodendrocyte progenitor cells (named “GRNOPC1”) . This phase I pioneering study was ended abruptly after only a year over financial feasibility concerns. It recruited only five participants and no official results were released, although in press releases the company indicated that the therapy was well-tolerated with no serious adverse events. While perhaps not adding any proof that SCT was a promising therapy, it broke the ice and paved the way for future studies. Now in 2016, according to there are at least 10 studies about to enroll or currently enrolling subjects for new studies and around 15 more have either been completed or are in the process of wrapping up. Most of these studies start off in rats, sometimes mice or even larger animals before moving into human studies.

Each study design includes a unique variety of factors. These include:

  • The type of stem cell they’ll use: oligodendrocyte precursor cells, neural stem cells, neural progenitor cells, mesenchymal stem cells and adult human olfactory bulb neural stem cells to name a few.
  • The type of SCI they’ll accept into the study.
  • The age of the injury they’ll accept: acute, sub-acute, chronic.
  • Type of injection: into injury site, IV, etc.
  • Different doses and dosing strategies.
  • Including a scaffold material or not.
  • Including different chemicals e.g. growth factors.
  • Other factors such as general health, patient’s history, medications the patient is using.

Some Exciting Ongoing Studies

StemCells, Inc. – Phase II Study
SCI type: neurologically complete, chronic, cervical SCI patients with the most severe degree of SCI by AIS.
Cell type: transplantation of HuCNS-SC human neural stem cells into the spinal cord region of injury
Six-month Interim Results: improvement in both muscle strength and motor function was detected in four of the six first cohort patients six months post transplant.

StemCells, Inc. – Phase I/I
SCI type: T2-T11 thoracic SCI with an A or B AIS rating
Cell type: transplantation of 20 million HuCNS-SC human neural stem cells into the spinal cord region of injury + 9-month course of immunosuppression
Top-line results reported: suggest a favorable safety profile and signs of biological activity and preliminary efficacy. Four out of eight subjects showed segmental sensory improvement.

Neuralstem – Phase I
SCI type: neurologically complete, chronic, T2-T12 thoracic SCI with an A AIS rating
Cell type: transplantation of 1.2 million human spinal cord-derived neural stem cells around the site of the spinal cord injury + physical therapy + 3 months immunosuppression.
Interim finding: well-tolerated by all four patients. One in four showed an ability to contract some muscles below the level of injury and this was confirmed via clinical and electrophysiological follow-up examinations.

The Miami Project – Multiple Studies
A number of phase I and II stem cell (and non stem cell) studies are taking place for acute and chronic SCI using autologous Schwann cells or HuCNS-SCs. Thus far it is very early in the process and thus there are no results as of yet.

Asterias Biotherapeutics – Phase I and Phase I/IIa
Phase I
SCI type: neurologically complete, acute, thoracic spinal cord injury
Cell type: 2 million human embryonic stem (hES) cell-derived oligodendrocyte progenitor cells (AST-OPC1) + 60 days of immunosuppression.
Results: no major safety issues and four of the five subjects showed a reduction of the volume of injury in the spinal cord in serial MRI scans.

Phase I/IIa
SCI type: neurologically complete, sub-acute, C-5 to C-7 SCI.
Cell type: 2 million a dose escalation starting with patients being dosed 2 million  human embryonic stem (hES) cell-derived oligodendrocyte progenitor cells that escalates into two patient cohorts at 10 million and 20 million cells, respectively.
Results: none yet.


Thus far, SCT for SCI has been shown to be well-tolerated by patients with no treatment-related serious adverse events. Now that safety and tolerability have been shown, the next step is to show efficacy. While many studies have only tried very small doses of cells, there have already been patients who showed improvement.  As it stands, phase I and II studies that are finished or wrapping up have been very different to each other making comparison difficult. Over the coming months and years, more studies will emerge with bolder regimes trying higher doses. Hopefully in these we’ll begin to see the peer-reviewed papers with statistically significant results that will better indicate which types of cells, doses and injection regimes work best for which types of SCI and the number of comparable studies will then increase to make review of this subject and thus a conclusion of the efficacy of SCT for SCI more clear.

Article by Olwen Reina. Contact Olwen at