MSC Therapy for Progressive MS: What Changed in 93 Patients’ Spinal Fluid

MedClinics News & Blog

The 2024 Phase II trial left the New York research team with an awkward result. Some patients who already needed help walking performed better on selected tests after receiving MSC-NPs. Bladder function and grey-matter loss also produced encouraging findings. Yet the results varied from one measurement-and one patient-to another.

The clinical scores could not explain that variation. They showed what patients were able to do at an appointment, but offered few clues about what the injected cells had been doing in the months between visits.

Fortunately, fluid samples had been collected during the trial. Before patients received another lumbar injection, the team took cerebrospinal fluid and stored it for later analysis. Those samples offered another way to examine MSC therapy for progressive MS: instead of looking only at disability, the researchers could search for changes close to the brain and spinal cord.

For the follow-up paper, Violaine K. Harris and colleagues studied samples from the 50 Phase II participants and 43 patients treated through expanded access. CCL2 and SCF became lower after treatment. MMP9 and CHIT1 became higher. Blood samples did not follow the same pattern.

None of these proteins can currently predict whether a patient will improve. Their relevance is more immediate to the trial itself. They provide a possible record of how the central nervous system responded after MSC-NPs were introduced.

The findings were published in Stem Cells Translational Medicine on 18 September 2026.

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The Samples Came From Treatment Days

This was not a newly organised 93-person trial.

The first set of samples belonged to 50 participants in an earlier randomized Phase II study. The second set came from 43 people treated through an expanded-access program. Both programs used the same cell product and were run at the Tisch MS Research Center.

Secondary progressive MS accounted for 73 of the 93 cases. Twenty patients had primary progressive MS.

The Phase II group was younger and, on average, less disabled. Their mean age was 50, compared with 58 in expanded access. The median EDSS score was 5.3 in the first group and 6.5 in the second.

An EDSS score of 6.5 generally describes someone who needs assistance to walk even a relatively short distance. This was not a population with mild or newly diagnosed disease.

The schedules were different too. Phase II participants received six treatments at two-month intervals. Those in expanded access received three, spaced three months apart.

The timing of the samples followed those schedules. In the Phase II trial, the later sample was collected before the sixth injection, by which point the patient had already received five doses. In expanded access, it was collected before the third, after two previous doses.

That difference later became relevant for SCF, which seemed to change more slowly than some of the other proteins.

Combining the groups increased the number of patients available for analysis, but the real advantage was replication. The researchers could find a possible marker in one group and see whether it behaved similarly in another.

What Patients Actually Received

Preparation of bone marrow-derived MSC-NPs for progressive MS research

The treatment started with a bone marrow sample from the patient.

Mesenchymal stromal cells were separated from that sample and grown in a controlled manufacturing facility. The laboratory then cultured them in a way that shifted their characteristics towards a neural progenitor-like profile. The final product was known as MSC-NP.

One dose could contain up to 20 million cells. Instead of entering a vein, the MSC-NPs were placed into cerebrospinal fluid through an injection in the lower back.

The word “neural” needs some context. These were not mature nerve cells, and the treatment was not built around the expectation that they would replace large areas of lost tissue.

The researchers were interested in the cells’ secretions. MSCs release many biological signals into their surroundings. Some affect immune cells; others alter inflammation or the behaviour of nearby tissue. The additional neural progenitor-like preparation was intended to produce a cell population suited to the environment of the central nervous system.

This makes MSC-NP treatment different from AHSCT, despite both being described with the broad language of stem cells.

AHSCT uses blood-forming stem cells after intensive conditioning of the immune system. MSC-NPs are derived from mesenchymal stromal cells and are delivered into cerebrospinal fluid without that chemotherapy-based immune reset.

The distinction is practical as well as biological. These patients returned for a series of lumbar injections over several months. They were not undergoing transplantation in the haematological sense.

A Pattern That Stayed in the Spinal Fluid

Cerebrospinal fluid biomarker analysis in an MSC-NP study for progressive MS

The first analysis cast a wide net across proteins in CSF. From that work, the researchers selected a smaller group that could be checked with conventional laboratory assays.

Some of the early candidates could not be measured reliably with the follow-up tests. Others showed no meaningful movement. Four continued to stand out.

CCL2 was the most familiar of them.

It is involved in attracting immune cells and has been found in inflammatory activity involving microglia and astrocytes. Earlier studies of intrathecal MSC treatment had also reported lower CCL2 in cerebrospinal fluid.

Levels fell again in this research.

SCF moved in the same direction. The name stands for stem cell factor, though it is a normal signalling protein found in several tissues and is not a count of the cells that were injected.

Its decrease was clear after five previous doses in the Phase II group. Among expanded-access patients, who had received two previous doses, the fall was less pronounced and did not reach statistical significance.

CCL2 and SCF were connected in another way. Patients who started with higher levels of one tended to have higher levels of the other. The size of their changes also tended to match.

The other half of the pattern ran upwards.

MMP9 increased, as did CHIT1.

For a reader, the temptation is to turn that into a simple scorecard: lower inflammatory proteins are good; higher inflammatory proteins are bad. The biology in this case does not cooperate.

MMP9 can take part in the breakdown of the blood–brain barrier during active MS. It also remodels the material between cells. Remodelling is involved in several very different processes, including changes at nerve connections and events that accompany myelin repair.

CHIT1 is linked with the activity of microglia and macrophages. An increase tells us that these cells, or processes associated with them, have changed. It does not tell us why. Laboratory studies have also raised the possibility that CHIT1-related activity may influence the development of oligodendrocytes.

Nobody can yet say whether the rise in MMP9 and CHIT1 was helpful, harmful or largely neutral. The study captured movement in the system; it did not reveal the final consequence of that movement.

The Saline Period Gave the Team a Useful Check

Twenty-six people in the Phase II trial had originally been assigned to saline. They later crossed over and received MSC-NPs.

Their earlier CSF samples offered a useful comparison. If repeated lumbar injections alone were responsible for the four-protein pattern, something similar should have appeared during the saline period. It did not.

CCL2, MMP9 and SCF remained stable after saline. CHIT1 decreased. Once treatment switched to MSC-NPs, CCL2 and SCF moved down, while MMP9 and CHIT1 moved up.

That comparison involved only part of the Phase II group, but it gives the result more weight. The response was linked more closely with the cells than with the procedure used to deliver them.

Blood samples added another piece.

The researchers measured the same proteins in serum from the Phase II participants. None changed significantly after treatment, and serum levels did not follow the CSF results in a consistent way.

The cells had been delivered into cerebrospinal fluid. That is where the signal appeared.

This may be the most practical outcome of the paper. In another MSC-NP study, the research team could measure these four proteins and see whether the expected reaction occurred. If it did not, questions about the dose or the potency of the cell product could be raised early.

What the panel cannot currently do is tell a patient whether the biological reaction will be followed by clinical improvement.

NfL and GFAP Told a Different Story

Neurofilament light chain and GFAP are already familiar in MS research, so both were included.

NfL is released when nerve fibres are injured. It often rises with active inflammatory damage. GFAP comes mainly from astrocytes and has drawn increasing attention in progressive disease.

NfL did not fall after MSC-NP treatment. It remained stable in the Phase II group and increased slightly in expanded access. GFAP was also stable.

Most participants entered the programs with non-active progressive MS and relatively low NfL. The absence of a large decline is therefore not entirely surprising.

There is also a technical point. The assays used for NfL and GFAP were not the newer ultra-sensitive methods now common in this field. A smaller change may have gone undetected.

At baseline, the measurements behaved much as expected. NfL rose with age. GFAP was related to age and disability.

They may still be useful for describing the patient and the disease. In these samples, they were poor indicators of what happened after MSC-NP injections.

The Clinical Trial Came Before the Biomarker Paper

Clinical assessment during an MSC-NP trial for progressive multiple sclerosis

The current publication did not set out to produce another list of walking scores. Those results belong to the Phase II paper published in 2024.

That trial compared MSC-NPs with saline using a crossover design. Its results were not uniform.

Among patients who already needed assistance to walk, some walking measurements improved after treatment. The researchers also reported changes in bladder function and less loss of grey matter. Other disability measures were less persuasive.

There are many ways to read such a result.

Progressive MS is not the same biological situation in every patient. One person may still have inflammation that can be influenced. Another may have little active inflammation but extensive damage left by earlier disease. Both can have the same diagnosis and a similar disability score.

The cells add another source of variation. Every MSC-NP product was grown from an individual patient’s marrow. Two preparations made by the same laboratory may meet all quality standards and still differ in the amount or balance of signals they release.

The new protein panel offers a possible way to examine those differences.

A future trial could compare the potency of each cell preparation with the change in CCL2, SCF, MMP9 and CHIT1. It could then follow the patients long enough to see whether a particular CSF response accompanies better walking or slower progression.

No such relationship was found in the present paper. People with the largest biomarker changes were not consistently the ones with the strongest clinical results.

What the Study Has Added

Before these findings, the Phase II trial had already provided reasons to continue the MSC-NP program. Some clinical measurements had improved, and the treatment had produced no signal that brought the study to a halt.

The biomarker work answers a different question. It shows that the central nervous system responded after the cells were introduced.

That response had a recognizable shape. It appeared in two patient groups. It was absent from the blood and looked different during saline treatment.

For future work on MSC therapy for progressive MS, this is more useful than simply knowing that “something” changed. Researchers now have four measurements they can follow from the first dose onwards.

The next study will have to do the harder part. It must place those measurements beside clinical outcomes over time and find out whether the pattern forecasts anything that matters to the patient.

Perhaps it will identify an effective dose. Perhaps it will expose weak cell preparations. It may help separate patients who respond biologically from those who do not.

Or the four proteins may turn out to be markers of exposure with little connection to function. That possibility remains.

What This Means for Patients Today

MSC-NP treatment has not become part of routine care for primary or secondary progressive MS.

The 93-patient figure should not be read as the number of people who improved. It is the number of treated participants whose biological samples contributed to this analysis.

The study also offers no personal test of likely benefit. CCL2, SCF, MMP9 and CHIT1 are research measurements, not biomarkers used in ordinary MS clinics.

Still, the paper moves the research beyond a simple account of injections and later disability scores. It identifies activity in the space between them.

For a treatment intended to work through cellular signals rather than direct replacement of damaged nerves, that information is useful. Its clinical value will depend on what happens next.

Frequently Asked Questions

Did all 93 patients belong to one trial?

The samples came from two programs at the Tisch MS Research Center. Fifty patients had joined a randomized Phase II trial, and 43 were treated through expanded access.

Were donor cells involved?

No donor supplied the MSCs. Each patient’s cell product was grown from mesenchymal stromal cells obtained from their own bone marrow.

Why were the cells injected into the lower back?

A lumbar intrathecal injection places the cells in cerebrospinal fluid, close to the brain and spinal cord. The researchers were trying to direct their biological signals towards the central nervous system.

Which laboratory results changed?

CCL2 and SCF became lower in cerebrospinal fluid. MMP9 and CHIT1 became higher. The same overall pattern was not present in serum.

Do the results mean that myelin was repaired?

Myelin repair was not demonstrated. Some of the proteins have possible roles in remodelling or oligodendrocyte biology, but the study could not show that these processes led to remyelination in the patients.