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Anti- N -methyl- d -aspartate (NMDA) receptor encephalitis is caused by altered patient immune reactions. This study reports the first patient with severe neurologic sequelae after NMDA receptor encephalitis treated with allogeneic umbilical cord–derived mesenchymal stem/stromal cells (UC-MSCs). A 5-year-old girl was diagnosed with NMDA receptor encephalitis and treated with immunosuppressive medicaments and intravenous immunoglobulin (IVIG). Despite intensive therapy, the patient’s condition worsened so that allogenic UC-MSC therapy was contemplated. The patient received three intrathecal infusions of xeno- and serum-free cultured UC-MSCs at a dose of 10 6 cells/kg. At baseline and after each UC-MSC administration, the patient was examined by the German Coma Recovery Scale (CRS), the Gross Motor Function Classification System (GMFCS), the Gross Motor Function Measure–88 (GMFM-88), the Manual Ability Classification System (MACS), the Modified Ashworth Scale, and the Denver II test. Before cell therapy, she was in a permanent vegetative state with diffuse cerebral atrophy. Her cognition and motor functions improved progressively after three UC-MSC infusions. At the last visit, she was capable of walking, writing, and counting numbers. Control of urinary and bowel functions was completely recovered. Cerebral atrophy was reduced on brain magnetic resonance imaging (MRI). Overall, the outcomes of this patient suggest a potential cell therapy for autoimmune encephalitis and its neurological consequences.

We recently reported a standardized xeno- and serum-free culture platform to isolate and expand umbilical cord-derived mesenchymal stem/stromal cells (UC-MSCs). Comparing populations from the same passage, cells that were cryopreserved and culture-rescued exhibited characteristics similar to those of their fresh counterparts, continuously cultured cells without interim cryopreservation. The culture rescue after thawing allowed for the cells to be fully recovered. However, since it would be more cost-effective and timesaving if cryopreserved cells can be used as an off-the-shelf product, we set out to compare the bioactivity of freshly thawed UC-MSCs versus culture-rescued UC-MSCs of the same batch that were recultured for an additional passage under our xeno- and serum-free protocol. UC-MSCs showed high viability in both the freshly thawed and the re-cultured group. Both populations displayed a similar proliferation capacity which is indicated by a comparable population doubling time and colony-forming ability. Both freshly thawed and culture-rescued UC-MSCs expressed the characteristic immunophenotype and were capable of differentiating into osteocytes, chondrocytes, and adipocytes. On the other hand, culture-rescued cells appeared to be more potent in immunosuppression than freshly thawed cells. In conclusion, freshly thawed and culture-rescued cell products share comparable bioactivity in cell growth and proliferation, immunophenotype, and differentiation potential. However, the culture-rescued cells that were allowed to grow for an additional passage appear to display a more favorable immunomodulatory potential when compared to their freshly thawed parent cells.