Mesenchymal stem cell-derived neural progenitors in progressive MS

Abstract

ObjectiveTo determine the long-term safety and efficacy of repeated intrathecal (IT) administration of autologous mesenchymal stem cell-derived neural progenitors (MSC-NPs) in patients with progressive MS by evaluating subjects 2 years after treatment.MethodsTwenty subjects were enrolled as part of a phase I, open-label single-arm study of 3 IT injections of MSC-NPs spaced 3 months apart. Subjects were evaluated for adverse events and disability outcomes including the Expanded Disability Status Scale (EDSS) and the timed 25-foot walk (T25FW). Long-term evaluation was conducted 2 years after the third treatment. CSF was collected before and 3 months after treatment.ResultsEighteen of the 20 study participants completed the full 2-year follow-up protocol. There were no long-term adverse events associated with repeated IT-MSC-NP treatment. Seven subjects showed sustained improvement in EDSS after 2 years, although the degree of improvement was not maintained in 5 of the subjects. Three of the 10 ambulatory subjects showed sustained improvement in the T25FW after 2 years. CSF biomarker analysis revealed a decrease in C-C motif chemokine ligand 2 (CCL2) and an increase in interleukin 8, hepatocyte growth factor, and C-X-C motif chemokine ligand 12 (CXCL12) after treatment.ConclusionsSafety and efficacy of repeated IT-MSC-NP treatment was sustained for 2 years; however, the degree of disability reversal was not sustained in a subset of patients. CSF biomarkers altered in response to IT-MSC-NP treatment may reflect specific immunoregulatory and trophic mechanisms of therapeutic response in MS.Classification of evidenceThis study provides Class IV evidence that for patients with progressive MS, IT administration of MSC-NPs is safe and effective. The study is rated Class IV because of the absence of a non–IT-MSC-NP-treated control group.Clinicaltrials.gov identifierNCT01933802.

Effect of Multiple Sclerosis Cerebrospinal Fluid and Oligodendroglia Cell Line Environment on Human Wharton’s Jelly Mesenchymal Stem Cells Secretome

“…On the other hand, there is an increased MCP-1 level after treatment with methylprednisolone [47,48]. Analysis of the CSF biomarker in patients after three intrathecal injections of MSCs-derived neural progenitors, revealed a decrease in MCP-1 and an increase in interleukin 8 levels, that confirmed the immunoregulatory properties of MSCs [49].…”

Stem Cell Therapies for Progressive Multiple Sclerosis

“…The tolerability of the treatment was established by a phase 1 doseescalating IT administration study in people with PMS, which supported feasibility and long-term safety with post-treatment improvement of clinical scores in 4 (out of 6) participants (Harris et al, 2016). A follow-up single-arm phase 1 study, comprising 3 IT treatments of MSC-NPs administered at 3month intervals, found an improved mean EDSS score over 12 months of follow-up sustained by 7 (out of 20) participants at 2 years (Harris et al, 2018(Harris et al, , 2021. Effects were found to be more pronounced in ambulatory (low/medium-disability) SPMS participants, rather than (non-ambulatory), PPMS participants.…”

“…Effects were found to be more pronounced in ambulatory (low/medium-disability) SPMS participants, rather than (non-ambulatory), PPMS participants. Clinical outcomes also included signs of improved muscle strength (70% of participants) and bladder function (50% of participants) (Harris et al, 2018), while cerebrospinal fluid biomarker changes, including a decrease in CCL2 and increases in IL-8, HGF, and CXCL12, were found to reflect treatmentrelated immunoregulatory and trophic effects (Harris et al, 2021). These outcomes have inspired an ongoing placebocontrolled phase 2 crossover trial (NCT03355365), which is recruiting 50 PMS participants to receive a total of 6 IT treatments at 2-month intervals, with functional outcomes (including clinical scores and bladder function) assessed over 36 months of follow-up.…”

Shining the light on clinical application of mesenchymal stem cell therapy in autoimmune diseases

“…In another long-term phase I clinical study which was conducted by Harris et al [ 67 ], 20 patients with progressive MS were enrolled. The patients from 2014 to 2016 received three times IT injections of autologous MSC-NPs at an average dose of 9.4 × 10 6 cells (target dose was 1.0 × 10 7 cells).…”