Hematopoietic and mesenchymal stem cell therapies explored

By Colleen Doherty, MD 

 Medically reviewed by Nicholas R. Metrus, MD

Multiple sclerosis (MS) treatment usually centers around disease-modifying drugs that help reduce relapses or “flare-ups” of symptoms and slow the natural progression of the disease. While these drugs are beneficial, stem cell therapies potentially offer more promise by putting patients into long-term remission and/or repairing the damage done by the disease.

This article will discuss the risks, benefits, and research behind two types of stem cell treatments being used or explored in MS care. These treatments include autologous hematopoietic stem cell transplant and mesenchymal stem cell transplant.

What Is Stem Cell Therapy for MS?

A stem cell is a single cell that can divide and replicate itself or turn into a specialized cell type like a nerve or blood cell. Stem cell therapy is any treatment that uses stem cells to ease or treat a condition.

Autologous Hematopoietic Stem Cell Therapy (aHSCT)

Autologous hematopoietic stem cell therapy (aHSCT) is a type of bone marrow transplant that attempts to “reset” a person’s immune system using hematopoietic (blood-forming) stem cells taken from the person’s own body.

What Cells Can Hematopoietic Stem Cells Form?

Hematopoietic stem cells give rise to red blood cells, white blood cells, and platelets.

The main goal of aHSCT is to eliminate a patient’s overactive immune system and create a new, healthy one. This treatment works best for patients with relapsing-remitting MS whose disease continues to be highly active and aggressive despite the use of various disease-modifying drugs.1

Since aHSCTs are still considered experimental for patients with MS, doctors use slightly different protocols when performing them.

That said, the basic steps of aHSCT include:2

• Preparation: You are given medication to help your body make more blood-forming stem cells. You may also be given medication to help the stem cells move from your bone marrow into your bloodstream.

• Collection: The blood-forming stem cells are collected from your bloodstream and frozen in a laboratory.

• Suppression: You are given chemotherapy in the hospital over a period of several days to suppress your immune system.

• Transplant: The frozen blood-forming stem cells are thawed and infused back into your bloodstream.

• Rebuild: The transplanted stem cells move from your bloodstream into your bone marrow, and your immune system begins rebuilding itself.

Mesenchymal Stem Cell Transplant

Mesenchymal stem cells are found in many tissues throughout your body, including your bone marrow, skin, and fat tissue.3

These cells are believed to have regenerative properties, providing support to the tissue’s natural repair process should that specific tissue become damaged. They may also help reduce inflammation and protect nerves from damage.

Mesenchymal stem cell transplant involves first isolating the stem cells from a patient’s fat, skin, or bone marrow. The cells are then multiplied in a laboratory or treated with special factors and delivered back into the body using various methods (e.g., injecting them into the bloodstream or through the spinal canal).

Once back in your body, the cells may calm your immune system down and encourage the repair of damaged myelin within your brain and spinal cord.

Myelin Repair in Progressive MS

The promotion of myelin repair in MS may be an especially useful treatment option for patients with progressive MS. These patients experience few or no “relapses,” but their symptoms slowly worsen over time, and they become more and more disabled.

Risks and Benefits

Research studies on autologous hematopoietic stem cell transplants in MS have consistently found the procedure to be beneficial. The safety of the procedure has also improved over the years.

One meta-analysis evaluated over 700 transplant patients from 15 different trials. After pooling together all the data, the investigators found that 83% of the patients had no evidence of disease activity two years after the transplant.1

In a 2021 study, 71% of the participants with relapsing-remitting MS and 57% of participants with progressive MS continued to experience no worsening of disability 10 years after their transplant.4

The risk of undergoing aHSCT is that when the immune system is suppressed, patients are vulnerable to potentially life-threatening bacterial, viral, and fungal infections.

Moreover, undergoing a transplant is costly and time intensive. Patients usually stay in the hospital for three weeks, and they may experience unpleasant side effects from the chemotherapy.

Research on mesenchymal stem cell transplantation is still in its very early phases. Most studies have been done on animals, although there are both ongoing and completed clinical trials in humans. Preliminary results seem to suggest that this therapy is safe and possibly beneficial.

In one phase 2 clinical trial, 16 patients with primary progressive or secondary progressive MS underwent three injections of mesenchymal stem cells into their spinal canal every two months.5 The stem cells had been treated with factors intended to help nerve cells grow and survive.

Results found that some of the study patients had improvements in mobility, finger dexterity, and cognitive and visual dysfunction. Headache and back pain from the lumbar punctures were the most commonly reported side effects. No deaths or treatment-related adverse events due to worsening of MS occurred in the study.

However, larger and longer-term studies and ones with control groups are needed to adequately determine whether mesenchymal stem cell transplants are safe and effective.5

Future Steps and Development

For autologous hematopoietic stem cell transplants, the next big step is seeing how a transplant compares to taking a disease-modifying drug, in terms of inducing long-term MS remission and improving quality of life.6

One clinical trial called BEAT-MS is already seeking to do this by comparing aHSCT to some of the most effective disease-modifying therapies used to treat relapsing MS.

The study is following 156 patients over six years. The MS drugs being compared include Tysabri (natalizumab), Lemtrada (alemtuzumab), Ocrevus (ocrelizumab), and Rituxan (rituximab).

For mesenchymal stem cell transplants, it’s really a matter of carrying out more human studies to tease apart issues like which cells are easiest, safest, and most effective to use (if any). How to best deliver the mesenchymal stem cells into the patients also requires further investigation.

Summary

Stem cell treatments involve using self-replicating cells, or cells that can turn into a specialized type of cell, to treat a condition. Autologous hematopoietic stem cell and mesenchymal stem cell transplants are experimental stem cell treatments being used or explored in MS care.

Research is much further along for autologous hematopoietic stem cell transplants and indicates that the procedure is effective and safe for patients with highly active relapsing-remitting MS.

Sources

Sormani MP, Muraro PA, Schiavetti I, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a meta-analysis. Neurology. 2017;88(22):2115-2122. doi:10.1212/WNL.0000000000003987

National Multiple Sclerosis Society. aHSCT in MS (autologous hematopoietic stem cell transplantation).

National Multiple Sclerosis Society. Mesenchymal stem cells and iPSCs.

Boffa G, Massacesi L, Inglese M, et al. Long-term clinical outcome of hematopoietic stem cell transplantation in multiple sclerosis. Neurology. 2021;10.1212/WNL.0000000000011461. doi:10.1212/WNL.0000000000011461

Bejargafshe MJ, Hedayati M, Zahabiasli S, Tahmasbpour E, Rahmanzadeh S, Nejad-Moghaddam A. Safety and efficacy of stem cell therapy for treatment of neural damage in patients with multiple sclerosis. Stem Cell Investig. 2019;6:44. doi:10.21037/sci.2019.10.06

Burt RK, Balabanov R, Burman J, et al. Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis. JAMA. 2019;321(2):165-174. doi:10.1001/jama.2018.18743

Shroff G. A review on stem cell therapy for multiple sclerosis: special focus on human embryonic stem cells. Stem Cells Cloning. 2018;11:1–11. doi:10.2147/SCCAA.S135415

By Colleen Doherty, MD
 Colleen Doherty, MD, is a board-certified internist living with multiple sclerosis.