Cell-Based Therapies: New Hope for the Treatment of Multiple Sclerosis

Mar 11, 2016 | Trends

Multiple sclerosis (MS) is an autoimmune/inflammatory disease that affects the brain, optic nerves and spinal cord (together called the central nervous system, CNS). It is an incurable, painful disease that affects 2.3 million people worldwide. Symptoms range from numbness and tingling to blindness and paralysis that progresses over time.

Traditionally, treatment for MS has been focused on symptom management through forms of immunosuppression. This is done using a combination of pharmaceutical drugs, plasmapheresis and deep brain stimulation. Here, we explore a cell-based technological solution that is a promising next step in MS treatment: stem cell therapies. First, let’s go over the basics of MS and cell-based treatments.

What is MS? What Causes It?

MS is characterized by T cell-activated mononuclear cell infiltration into the CNS and by an immune attack on the myelin protective sheath covering neuronal cell fibers. The resulting damage leads to a reduction or even a loss of function over time. The myelin sheath is an insulating layer surrounding nerve cells allows them to conduct neural impulses and it is this sheath that it the target of autoimmune damage. As the myelin is lost, the neurons lose their ability to conduct signals and overtime even the neurons themselves become damaged. While the disease starts with this neuroinflammation (called relapsing-remitting MS), as it progresses the immune cell involvement dies down and the disease at this point is characterized by neurodegeneration (called progressive MS), as large numbers of neurons are now stripped of their myelin. Currently, there are no treatments options available that reverse this neurodegeneration but stem cell therapy research offers potential options in the future (see oligodendrocyte precursor cell therapy research below).

It is not known what causes MS but there are genetic dispositions and perhaps an environmental effect may also play a part. Currently, there is no cure but there are treatment options that can help to manage the disease symptoms and promote remission and recovery from attacks during the relapse-remission stage.

What are Cell-Based Therapies?

“Cell-based therapies” are the transplantation, delivery or stimulation of cells in the hope of positively affecting nervous system repair and dampening autoimmune responses. Such therapies include somatic cell, dendritic cell and T cell-based treatments. While some cell-based therapies are in clinical use for other diseases like cancer, they are relatively new and so there is still a long way to go. In this article, we’ll focus on some of the stem cell therapies currently being evaluated as MS interventions: hematopoietic stem cells, mesenchymal stem cells and oligodendrocyte precursor cells. Thus far, none of these therapies are freely available for routine clinical use but are mainly restricted to clinical trials, animal studies and cell studies.

Hematopoietic Stem Cells (HSCs)

HSCs are found in the bone marrow, umbilical cord blood and blood. They have been studied as potential treatments for MS for about 2 decades and we’ve learnt much during this time. Here, a hard reboot is done on an MS patient’s immune system. This aggressive treatment is also used for lupus, rheumatoid arthritis, and type 1 diabetes. There are four steps for HSC transplantations (HSCT):

  1. HCSs are stimulated, captured and stored.
  2. The immune system is depleted using chemotherapy and/or radiation therapy.
  3. HSCs are reintroduced.
  4. HSCs migrate to the bone marrow and, over time, repopulate the immune system.

The cells used can be autologous (patient’s own cells) or allogeneic (cells from a donor) but autologous is more common (commonly referred to as AHSCT).

A recent study showed that from a cohort of 123 people with relapsing-remitting MS, AHSCT was linked to a 64% reduction in disability on average. Despite this promising results and others like it, there are huge safety risks, mainly due to the need to totally ablate the patient’s immune system. This leaves them very susceptible to infection in the 12 or so months it takes for the immune system to be repopulated and such it has a mortality rate of 1.3%.

Another downside is that such transplants are currently only open to relapsing-remitting stage MS patients and only then as part of clinical studies. There are also other restrictions. However, it is very effective in some people and offers MS patients another treatment option where before there was none.

Mesenchymal Stem Cells (MSC) and MSC-Derived Neural Progenitor Cells (MSCNPs)

MSCs are found in many parts of the body including the bone marrow, fat tissue, umbilical cord tissue, amniotic fluid and adipose tissue. They are currently being investigated as a potential therapy for reversing neurodegeneration. Mesenchymal stem cells have the potential to turn into several types of tissues and they are thought to also encouraging the body’s natural repair mechanisms. There are three steps to transplants:

  1. An individual’s MCS are isolated.
  2. Cells are cultured in the lab to increase their purity and numbers.
  3. They are then reintroduced into the body by intravenous (into the vein) or intrathecally (by lumbar puncture) injection.

A subtype of MSCs that has become particularly interesting in MS research and is now commonly used in MSC studies are MSCNPs which have been found to have immune regulatory and pro-myelination properties in mice. Less is known about how MSCs and MSCNPs work and how well they’re tolerated but a phase I study with the Tisch MS Research Center NY has shown that they are well-tolerated and that the next step is to examine different sources of MSCs, different routes of administration, different dosages and different injection schedules. Tisch has recently received approval for a phase II clinical study.

Oligodendrocyte Precursor Cells (OPCs)

OPCs are the endogenous stem cell population in the CNS. They differentiate into oligodendrocytes capable of both remyelinating cells and repairing neuronal damage. In late-stage MS, these OPCs are present but fail to differentiate. Two methods of harnessing these cell as a therapy are being explored:

  1. Stimulating their differentiation by manipulation of their microenvironment and
  2. Implanting OPCs into sites of neuroinflammation that are directly capable of inducing remyelination of the damaged axons.

Studies in mice using human OPCs have already proven effective. Another approach is to promote OPC transport to the site of MS lesions, a school of thought that fits very well with the former ideas. While not currently being tested in humans with MS, OPCs might be useful in repairing the nervous system. It is thought that they could be used to regrow the cells that make myelin: oligodendrocytes. OPCs live in the brain and are responsible for repair. Human or murine OPCs can be grown and expanded in vitro and then injected into MS animal models.

Another approach is being explored by the Salzer lab. In 2015, they published a paper showing that by chemically blocking Gli1 you could stimulate the myelin-repairing properties of oligodendrocytes in vivo in murine models of MS (Experimental Autoimmune Encephalomyelitis, EAE). While results found in mouse MS models like EAE don’t often carry through to humans, the principle here is intriguing.


While the use of stem cells as a therapy is not a recent concept, translational research has only recently started to see the emergence of clinical studies promising enough to suggest a clinically-available therapy isn’t far off. More controlled clinical trials are needed to figure out the optimal types of stem cells, sources for stem cells (such as induced pluripotent stem cells vs. the native cell type population) which route of delivery, and which types and stages of disease, would be the most promising approach for treating MS. Additionally, drugs that directly stimulate stem cells in vivo are another possibility.

Certainly, stem cells therapies offer potential as MS solutions that may slow-down and even reverse MS. Tell us what cell-based technologies you’ve read about and what you think of stem cell therapies in the comments below!

Article by Olwen Reina. Contact Olwen at olwen@tempobioscience.com.