Wharton's Jelly-Derived Mesenchymal Stem Cell Transplantation in a Patient with Hypoxic-Ischemic Encephalopathy: A Pilot Study

Abstract

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been introduced as a possible therapy in hypoxic-ischemic encephalopathy (HIE). We report a 16-year-old boy who was treated with WJ-MSCs in the course of HIE due to post-cardiopulmonary resuscitation. He received a long period of mechanical ventilation and tracheostomy with spastic quadriparesis. He underwent the intrathecal (1×10⁶/kg in 3 mL), intramuscular (1×10⁶/kg in 20 mL) and intravenous (1×10⁶/kg in 30 mL) administrations of WJ-MSCs for each application route (twice a month for 2 months). After stem cell infusions, progressive improvements were shown in his neurological examination, neuroradiological, and neurophysiological findings. To our best knowledge, this is a pioneer project to clinically study the neural repair effect of WJ-MSCs in a patient with HIE.

Keywords: hypoxic-ischemic encephalopathy; post-cardiopulmonary resuscitation; stem cell therapy; wharton’s jelly.

Fig. 1.

(A,B) cranial MRI including DWI sequences; after 4 days post-CPR demonstrated increased signal intensity in the bilateral anterior/ posterior watershed zone, basal ganglia, and occipital lobes; (C,D) after 6 months from the insult and 3 months a.f.i. showed no pathological signal; (E,F) after 12 months from the insult and 9 months a.f.i. showed no pathological signal.

Fig. 2.

(A,D) Morphology of cultured WJ-MSC at P3, (B) morphology and (C) Oil Red O Staining of neutral lipid vacuole formation in WJ-MSC cultured in adipogenic differentiation medium, (E) mineral nodules that stained by Alizarin Red S, of WJ-MSCs cultured in osteogenic differentiation medium, (F) Alcian Blue Staining of WJ-MSCs cultured in chondrogenic differentiation medium, (G) flow cytometric analysis of cell surface markers of WJ-MSCs at P3, (H) chromosome karyotype analysis of the cultered WJ-MSCs.