Stem cell therapy for multiple sclerosis

Last updated Oct. 24, 2022, by Marisa Wexler, MS
Fact-checked by Ines Martins, PhD

Multiple sclerosis (MS) is an inflammatory disorder that causes damage in the brain and spinal cord, which can lead to a range of symptoms, including fatigue, depression, muscle spasms, and difficulty regulating the bladder and bowels. Several strategies using stem cells — self-renewing cells in the human body — are being explored as potential treatments for MS.

What are stem cells?

The majority of cells in the adult body are terminally differentiated, meaning they are fully mature and cannot grow into another cell type — a liver cell cannot turn into a brain or skin cell, for example. Stem cells are the undifferentiated cells in the body that are capable of self-renewing and have the potential to grow into all other types of cells. When these cells divide, they can originate a similar stem cell and a more differentiated cell, two daughter stem cells, or two more differentiated cells.

Stem cells play a key role in early development, and they are important for facilitating repair when the body’s tissues are damaged. For some types of tissue with rapid cell turnover, such as blood cells or the inner lining of the intestines, stem cells act as a source of self-renewal to continually regenerate cells that are lost.

These cells generally are divided into two main forms. Some are pluripotent, meaning they are able to grow into every single type of cell found within the human body. Pluripotent stem cells are mainly involved in early development and have been employed for cell studies in laboratories as they can be grown into other cell types.

Other stem cells are multipotent, meaning they can grow into some types of cells but not others — for example, hematopoietic stem cells can give rise to all blood cells, but not to other cell lineages, such as bone or nerve cells.

Different types of stem cells

There are a number of different stem cells, each with specific biological properties. Stem cell types that have been used in MS research include:

• hematopoietic stem cells, or HSCs, also known as blood stem cells. These multipotent cells, residing in the bone marrow, give rise to all blood cells in the body, including red blood cells that carry oxygen, and white blood cells that make up the immune system.
• mesenchymal stem cells (MSCs), which can grow into bone, cartilage, and fat cells, as well as various other types of organ cells. They also secrete many signaling molecules that coordinate the activity of surrounding cells.
• neural stem cells (NSCs). As the name implies, these cells are able to grow into neurons, or nerve cells. These multipotent cells also can differentiate into other brain cells, such as astrocytes, which provide support to nerve cells, and oligodendrocytes, the cells chiefly responsible for producing myelin — a fatty wrapping around nerve fibers that is damaged in MS.
• embryonic stem cells, or ESCs, which are pluripotent cells found in embryos during prenatal development. A few studies have explored ESC-based therapies in animal models, but there is minimal research involving humans outside of a few case reports. In addition to the ethical issues surrounding the use of cells from human embryos, a potential concern about ESCs is that these cells may cause tumors due to uncontrolled cell growth.
• induced pluripotent stem cells (iPSCs), made in the laboratory by “reverse engineering” differentiated cells, usually mature cells from the skin or blood. There is minimal research into iPSC-based treatments in people with MS, and as with ESCs, there is a concern that iPSCs could grow out of control to cause tumors. However, iPSCs are commonly used as a research tool, especially because they can be grown into neurons and other cells that are normally hard to access.

No stem cell therapy has been approved by the U.S. Food and Drug Administration (FDA) specifically to treat people with MS. But some stem cell-based therapies are in clinical testing for MS, and hematopoietic stem cell transplants are already cleared for use in certain blood disorders. HSCs and MSCs have thus far been the most used and tested for MS.

Hematopoietic stem cells (HSCs)

HSCs reside in the bone marrow and give rise to all the cells in the blood, including most cells in the immune system. Because MS is caused by a faulty immune system, these cells are sometimes used to help manage MS via a one-time treatment called a hematopoietic stem cell transplant, in which these cells are infused into a patient.

While it is possible to do the transplant with cells collected from a donor, HSC transplants in MS are more commonly autologous, meaning they use stem cells collected from the patient. This procedure is called an autologous hematopoietic stem cell transplantation (aHSCT).

When used in the context of MS, the terms “stem cell therapy,” “stem cell transplant,” “bone marrow transplant,” or “blood stem cell transplant” usually refer specifically to aHSCT.

The basic goal of aHSCT is to reset a person’s immune system in an attempt to reduce the excess inflammation that drives MS. There is no one standardized protocol for aHSCT in MS, and various regimens may be used.

Typically, patients are first treated with medications to induce the production of more HSCs and stimulate their release (or mobilization) from the bone marrow into the bloodstream. This enables the collection of HSCs directly from the bloodstream, although some protocols skip the mobilization step and harvest cells directly with a bone marrow aspiration, which uses a special needle to collect a sample from the patient’s bone.

After the cells are harvested, the patient receives treatments like chemotherapy and/or radiation therapy that aim to completely wipe out the immune system — and specifically the abnormal immune cells causing neuronal damage. Finally, the HSCs are infused back into the patient to repopulate the immune system with healthy cells.

The procedure usually involves several weeks spent in a hospital. Before going home, patients have to wait for the HSCs to settle in the bone marrow and start producing healthy immune cells that can protect from infections. Because the immune system generally takes about one year to fully rebuild, there also are some recommended precautions to avoid infections after discharge.

While stem cell transplant is not specifically authorized by the FDA for MS, the National MS Society has supported aHSCT as a feasible treatment option for select patients with relapsing-remitting MS (RRMS).

These patients include individuals younger than 50 with disease duration less than 10 years who experienced continued disease activity — relapses and/or MRI activity — despite treatment with highly effective disease-modifying therapies (DMTs), or who are unable to take these medications.

How effective is HSC therapy for MS?

Studies have generally been consistent in showing treatment with aHSCT can reduce relapse rates and slow disability progression in people with MS — especially younger patients with highly active disease. Many patients also reported an improvement in quality of life and a reduction in MS symptoms after the transplant.

A 2022 meta-analysis — where researchers pool data from many previously published studies — examined disease outcomes after aHSCT in 4,831 people with MS. The data came from 50 published studies, including eight clinical trials.

Five years after the procedure, 73% of patients were alive and without disability progression, 81% were relapse-free, and 68% had no evidence of disease activity. No disease activity means these patients had no relapses, no worsening disability, and no new damage detected on MRI scans.

Several factors affect the efficacy of aHSCT for MS, including:

• type of MS: outcomes from aHSCT are generally better for people with RRMS than those with primary progressive MS.
• age: aHSCT generally is more effective in younger patients, particularly those younger than 50 years old.
• disease duration: the procedure is most effective early in the disease course, usually within the first decade after symptom onset.
• MS activity: aHSCT typically is more effective and durable in patients with highly active disease (multiple relapses or MRI lesion activity).
• disease severity: patients with accumulating disability who still retain the ability to walk are most likely to benefit from aHSCT.

Is HSC therapy for MS safe?

Early transplant-related complications, like fever, diarrhea, and low blood cell counts, are common after the aHSCT procedure.

More rarely, serious complications may occur. For example, because aHSCT involves wiping out the immune system, patients undergoing the procedure may be more vulnerable to infections and certain cancers, necessitating appropriate precautionary care.

Also, aHSCT can lead to early menopause and fertility problems, especially when more intensive chemotherapy regimens are used.

As with any complex surgical procedure, there is a risk of treatment-related death in aHSCT, although modern care has dramatically lowered mortality rates. Older trials have reported transplant-related mortality as high as 20%, but this figure is at about 4% for studies conducted between 2002 and 2021. Moreover, that figure drops to nearly 0% in studies using low-intensity chemotherapy.

Researchers have noted that stem cell transplant is an emerging area of medical tourism, in which patients travel to other countries with the intent of accessing medical care that is not easily accessible in their home country. However, many clinics offering this treatment lack adequate expertise to minimize the complications of aHSCT.

It is recommended MS patients considering aHSCT consult with their medical care team to choose an adequate treatment center, and determine which medical professionals should be involved in their care during and after the procedure. A list of accredited aHSCT centers in the U.S. is available on the Foundation for Accreditation of Cellular Therapy (FACT) website.

Ongoing clinical trials of stem cell transplant

Several ongoing studies are evaluating the safety and efficacy of aHSCT in people with MS, and comparing its outcomes against treatment with highly effective DMTs.

• BEAT-MS (NCT04047628) is comparing aHSCT against the best available DMT in people with highly active, treatment-resistant MS. The Phase 3 trial aims to enroll up to 156 people, ages 18 to 55, across more than 20 sites in the U.S. and one in the U.K.
• StarMS (ISRCTN88667898) is evaluating the use of aHSCT versus highly effective DMTs, including Mavenclad (cladribine), Lemtrada (alemtuzumab), Kesimpta (ofatumumab), and Ocrevus (ocrelizumab). The trial, launched in 2020, is recruiting people with highly active RRMS, ages 16 to 55, at more than a dozen sites in the U.K.
• RAM-MS (NCT03477500) is a Phase 3 clinical trial testing aHSCT against Lemtrada, Mavenclad, or Ocrevus in RRMS patients who had significant inflammatory activity in the previous year. An estimated total of 100 participants, ages 18 to 50, are being enrolled at sites in Denmark, the Netherlands, Norway, and Sweden.

There also are ongoing observational studies (NCT02674217) tracking the long-term outcomes of MS for patients who undergo aHSCT. Some of these studies, including one in California (NCT05482542), are comparing the safety and efficacy of different aHSCT procedures.

Mesenchymal stem cells (MSCs)

Mesenchymal stem cells, or MSCs, have potent immune-modulating properties that tend to promote an anti-inflammatory effect. These cells have been explored as a potential basis for therapies in multiple sclerosis.

Preclinical research has suggested MSC therapies can reduce inflammation and slow disease progression in models of MS.

MSCs are usually collected from bone marrow or adipose (fat) tissue, but MSCs derived from the blood and human umbilical cords have also been used in some studies. Like HSCs, mesenchymal stem cells can be collected from a healthy donor, but the most common practice in MS involves the use of autologous (from-the-self) cells, which don’t require patient-donor matching.

In addition to the different sources of MSCs, other factors contribute to a significant variability among MSC-based therapies. For example, the collected cells can either be expanded in the laboratory to several millions before being infused, or they can be expanded and treated with certain chemical cues to acquire greater immunosuppressive and neuroprotective characteristics.

Further, administration can vary. MSCs may be given via infusion into the bloodstream or through injection into the spinal canal. The interval between administrations also may vary.

How effective is MSC therapy for MS?

While numerous clinical trials have explored MSC-based therapies in people with MS, none have been definitive on efficacy. Almost all studies conducted thus far were small, early trials without a control group, and were mainly designed to assess the safety of different MSC treatment protocols.

Some early studies have reported these treatments reduced inflammation, eased disability, and/or improved quality of life, but other studies have not found consistent results. Therefore, the effectiveness of MSC-based treatments remains unclear.

Is MSC therapy for MS safe?

Because research on MSC therapies in MS is still in early stages, the safety profile of these potential treatments is incompletely understood. However, these treatments do not compromise a person’s immune system like aHSCT does, and most studies to date have not reported any serious safety concerns related to MSC therapies.

Side effects such as fever, headache, urinary tract infection, and fatigue have been reported in some studies.

Ongoing clinical trials of MSC therapies

An MSC-based therapy called IMS001 is being developed as a potential treatment for MS by ImStem Biotechnology. The experimental treatment is derived from human embryonic stem cells and is being evaluated in people with MS in a preliminary Phase 1 clinical study (NCT04956744). The trial is recruiting 30 participants at sites in the U.S.

Another MSC-based therapy, UMSC01, is being developed by Ever Supreme Bio Technology as a potential therapy for MS and other conditions. The therapy uses umbilical cord MSCs isolated from healthy donors. A Phase 1/2 trial (NCT05532943) testing UMSC01 in about 40 patients with RRMS or secondary progressive MS is ongoing.

BrainStorm Cell Therapeutics also is developing an MSC-based therapy. With NurOwn, a patient’s own bone marrow MSCs are matured in the lab to produce large amounts of neurotrophic factors which promote nerve cell growth and survival. In a Phase 2 clinical trial (NCT03799718), 18 people with progressive types of MS received NurOwn via three spinal canal injections, two months apart. Results showed the treatment to be generally well-tolerated, and some participants experienced clinically meaningful improvements in disability measures after treatment.

Other clinical studies also are ongoing, including a Phase 1/2 trial (NCT04749667) in Norway testing MSCs in progressive forms of MS; a U.S.-based Phase 2 trial (NCT05116540) investigating MSCs from adipose tissue in RRMS patients; and an early Phase 1 trial (NCT05003388) of umbilical cord MSCs called AlloRx, with study sites in Antigua and Barbuda, Argentina, and Mexico.

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