Mesenchymal Stem Cell-Based Therapy for Cerebellar Ataxia: From Bench to Bedside

Cerebellar ataxia (CA) encompasses hereditary and acquired disorders unified by Purkinje cell loss and neuroinflammation, for which no disease-modifying therapy exists. Human mesenchymal stem cells (hMSCs) offer multimodal neuroprotection through paracrine secretion of neurotrophic factors and immunomodulatory mediators.

We reviewed preclinical and clinical evidence for hMSC therapy across multiple CA etiologies, integrating findings from neuroinflammatory, toxic/developmental, and genetic mouse models alongside published clinical trials and case reports. A systematic literature search was conducted in PubMed/MEDLINE, Embase, and the Cochrane Library (search period: 2000-2026) using the following key terms: "mesenchymal stem cell" AND "cerebellar ataxia"; "MSC" AND "spinocerebellar ataxia"; "hMSC" AND "Purkinje cell"; "stem cell therapy" AND "ataxia". Inclusion criteria encompassed: peer-reviewed original research articles and reviews in English; in vivo animal model studies; clinical trials, case series, and case reports. Studies addressing non-CA neurological conditions without CA-relevant data were excluded.

hMSC transplantation consistently improved motor function, preserved Purkinje cell integrity, and attenuated neuroinflammation across LPS-induced, Ara-C-induced, and SCA2 transgenic models. A critical observation is that MSCs from CA patients exhibit markedly reduced anti-inflammatory secretome capacity compared with healthy-donor MSCs, justifying an allogeneic strategy. Therapeutic efficacy was maintained even after symptom onset in the SCA2 model. A published case report demonstrated safety and preliminary functional benefit of intrathecal allogeneic bone marrow-derived MSCs in a sporadic adult-onset ataxia patient.

hMSC therapy targets convergent CA pathomechanisms-microglial suppression, neurotrophin restoration, and Purkinje cell preservation-through a paracrine rather than cell-replacement mechanism. Post-symptomatic efficacy and an emerging clinical evidence base support advancing toward placebo-controlled randomized trials.