Author Affiliations: Departments of Neurology, AHEPA University Hospital, Thessaloniki, Greece, and Thessaly University Hospital, Larissa, Greece.
We read with considerable interest the exploratory study by Karussis et al1 on the safety of intrathecally transplanted mesenchymal stem cells (MSCs) in patients with multiple sclerosis (MS) and those with amyotrophic lateral sclerosis (ALS). Nevertheless, the data presented in that study1 do not clearly support the positive conclusion drawn, at least in MS.
More specifically, the scientific basis of the intrathecal route is limited because there is only 1 relevant study on the animal disease model.2 Additionally, there is, to our knowledge, no scientific evidence that the presence of MSCs within the central nervous system (CNS) is an absolute necessity for the effect these cells might have in autoimmune demyelination.
Based on magnetic resonance imaging (MRI) findings, the presence of any significant unexpected pathology up to the 6-month follow-up may not be totally excluded because the unpredicted behavior of MSCs within the CNS at the microscopic level3 might potentially be harmful, though clinically silent or undetected by a 1.5-T MRI scanner. Moreover, it is questionable whether the transplanted MSCs migrated toward MS lesions as expected2 because no relevant MRI finding was evident according to the data.1
Although, based on previous in vitro studies, the authors accept that there is a low risk of treatment-related malignant neoplasm induction, recent data indicate the spontaneous malignant transformation is biohazard in long-term ex vivo expansion of human MSCs.4
Finally, the immunomodulatory effects induced by the intravenously administered MSCs lack any evidence about T-helper 17 lymphocyte (Th17) response profiles in treated patients, thereby imposing further weakness on the concept of safety despite the profound reduction of other proinflammatory factors or the increase of regulatory T cells in patients who received transplants. In addition, recent preliminary data5 indicate that MSCs may induce Th17 responses concomitantly with Th1 response suppression. Such behavior of migrated MSCs might potentially exacerbate immune reactions within the CNS, in situ.
Within the emerging and promising field of regenerative medicine, the results and conclusions of clinical studies describing cell-based therapies should be interpreted with great caution to minimize any treatment-related harm to the already-unfortunate patients.
Correspondence: Dr Karacostas, Department of Neurology, AHEPA University Hospital, Thessaloniki 54636, Greece (bneurol@med.auth.gr).
Financial Disclosure: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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