Intrathecal administration of MSC secretome: benefits and risks

Intrathecal application means that the preparation is delivered by lumbar puncture into the cerebrospinal fluid. A thin needle is placed into the subarachnoid space of the lumbar spine, below the end of the spinal cord. From there the fluid bathes the spinal cord, the nerve roots and the surface of the brain.^[1]

The same access is used every day in neurology for CSF diagnostics, for spinal anaesthesia and for approved intrathecal medicines. In ALS, tofersen is given by this route.^[12]

Because this route places the preparation inside the central nervous system from the outset. After an infusion into a vein, extracellular vesicles are cleared from the blood within minutes. They are taken up mainly by liver, spleen and lung, and only a small fraction reaches the central nervous system.^[5],[6] Intrathecal administration places the preparation inside the central nervous system from the outset, so the blood–brain barrier does not lie on this route.^[1]

In external preclinical studies, intrathecally administered extracellular vesicles distributed widely in the central nervous system and were taken up by neurons, in mice and in non-human primates.^[11] That the route reaches the nervous system is therefore well supported. It does not show that MSC secretome is effective. There is no controlled clinical trial of MSC secretome in ALS.

Distribution is not uniform. Structures next to the cerebrospinal fluid are exposed most: the spinal cord, the nerve roots and the surfaces of brainstem and brain. Deeper regions of the brain are reached to a lesser and more variable degree.^[9]

It is carried out under local anaesthetic by your treating physician and takes only a few minutes. The plan is individual and usually follows this sequence:

• Before the application: no routine MRI is needed. We only arrange imaging of the lumbar spine when there is a reason for it — previous spinal surgery, a known spinal deformity, or symptoms that point to a problem at the puncture site.
• Who performs it: your treating physician at ANOVA IRM. Where imaging guidance is used, a radiologist performs the puncture — for example Dr Stehling.
• Imaging: there is no routine CT before an intrathecal application. CT guidance is optional and used only when the anatomy calls for it — after spinal surgery, with pronounced scoliosis, with marked facet joint arthrosis, or when an earlier puncture without imaging was difficult.
• Anaesthesia: a local anaesthetic at the puncture site. Where it is useful, one of our anaesthetists monitors the procedure.
• Afterwards: you stay with us for about one to one and a half hours. The anaesthetist or your treating physician then discharges you.

Imaging is carried out in the same building, which is why CT-guided punctures are possible at short notice. The diagnostic pathway is described on our diagnostics page.

An intrathecal application is a standard procedure carried out in many clinics every day, and its most common complication is post-dural-puncture headache; bleeding and infection are rare. Your doctor discusses the risks with you beforehand and documents your consent.

• Post-dural-puncture headache is the most common complication. It usually appears within two days and subsides on its own; rest, fluids and simple pain relief are the usual measures.
• Back pain at the puncture site and transient paraesthesia may occur and are usually short-lived.
• Bleeding and infection are rare. They are the reason for sterile technique, for asking about blood-thinning medication, and for checking the skin at the puncture site.

What we do: the puncture is performed by physicians who carry it out regularly, under sterile conditions and, where the anatomy calls for it, under CT guidance. You remain under observation afterwards and are discharged by a physician. In published clinical studies of intrathecally administered extracellular vesicles, the adverse events reported related predominantly to the puncture itself; long-term data are not available.

In most cases the initial assessment already shows whether an intrathecal application is possible for you. We ask about previous spinal surgery, spinal deformities, earlier punctures, blood-thinning medication and infections.

Reasons can also arise at short notice, for example an acute infection at the puncture site, newly started anticoagulation or an acute increase in intracranial pressure. In that case we postpone the application or, after medical assessment, discuss the intravenous route with you.

In short: the route delivers the preparation where it is needed, but it is more invasive than an infusion.

What speaks for this route

• The preparation is delivered into the central nervous system directly; no barrier lies on the route.
• Structures adjacent to the cerebrospinal fluid — spinal cord and nerve roots — are exposed most, which is where the target lies in ALS and in spinal cord injury.
• The access is routine in neurology and is used for approved intrathecal medicines.

What speaks against it

• It is more invasive than an infusion and carries the risks of a puncture.
• Distribution in the nervous system is not uniform; deep regions of the brain are reached less reliably.
• Not every patient is suitable; anatomy and medication can rule the route out.
• Reaching the nervous system is not the same as clinical benefit: the efficacy of MSC secretome is not established.

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Questions people usually ask next. Each is answered in full on its own page.

• Who are we?
• Is ANOVA legal?
• Is stem cell therapy safe?
• What is MSC secretome (MSEC)?
• What is BMC (Bone Marrow Concentrate)?
• What are stem cells?
• What should I ask when looking for a stem cell treatment?
• Which conditions do we treat?
• Does the secretome pass the blood–brain barrier?

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ANOVA IRM shares its premises in Offenbach with two further institutions owned by Dr. Stehling: the Institut für Bildgebende Diagnostik (IBDO), providing MRI and CT imaging, and the Vitus Prostate Center. Because imaging is carried out in the same building, condition-specific diagnostics — including CT-guided procedures — are performed in-house rather than referred elsewhere. See diagnostics at ANOVA IRM.

• [1] Pardridge WM. Drug transport in brain via the cerebrospinal fluid. Fluids Barriers CNS. 2011;8:7.
• [5] Wiklander OPB, Nordin JZ, O'Loughlin A, et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles. 2015;4:26316.
• [6] Kang M, Jordan V, Blenkiron C, Chamley LW. Biodistribution of extracellular vesicles following administration into animals: a systematic review. J Extracell Vesicles. 2021;10(8):e12085.
• [9] Iliff JJ, Wang M, Liao Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes. Sci Transl Med. 2012;4(147):147ra111.
• [11] Lam BWS, Tan M, Gao C, et al. Extracellular vesicles administered via intrathecal injection mediate safe delivery of nucleic acids to the central nervous system for gene therapy. J Extracell Vesicles. 2025;14(7):e70116.
• [12] Miller TM, Cudkowicz ME, Genge A, et al. Trial of antisense oligonucleotide tofersen for SOD1 ALS. N Engl J Med. 2022;387:1099–1110.
• [17] Penn RD, Savoy SM, Corcos D, et al. Intrathecal baclofen for severe spinal spasticity. N Engl J Med. 1989;320:1517–1521.
• [18] Ertzgaard P, Campo C, Calabrese A. Efficacy and safety of oral baclofen in the management of spasticity: a rationale for intrathecal baclofen. J Rehabil Med. 2017;49(3):193–203.
• [19] Siderowf A, Concha-Marambio L, Lafontant D-E, et al. Assessment of heterogeneity among participants in the PPMI cohort using α-synuclein seed amplification: a cross-sectional study. Lancet Neurol. 2023;22(5):407–417.