Published online Mar 20, 2021. doi: 10.5493/wjem.v11.i2.17
Peer-review started: December 24, 2020
First decision: January 18, 2021
Revised: February 19, 2021
Accepted: March 12, 2021
Article in press: March 12, 2021
Published online: March 20, 2021
Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in the adult as well as in the neonate, with limited options for treatment and significant dysfunctionality.
To investigate the safety and preliminary efficacy of allogeneic mesenchymal stem cells (MSCs) in HIE patients.
Patients who had HIE for at least 6 mo along with significant dysfunction and disability were included. All patients were given Wharton’s jelly-derived MSCs at 1 × 106/kg intrathecally, intravenously, and intramuscularly twice a month for two months. The therapeutic effects and prognostic implications of MSCs were evaluated by multiple follow-ups. Functional independence measure (FIM), modified Ashworth, and Karnofsky scales were used to assess any side effects, neurological and cognitive functions, and overall outcomes.
The 8 subjects included in the study had a mean age of 33.25 ± 10.18 years. Mean HIE exposure and mean post-HIE durations were 45.63 ± 10.18 and 19.67 ± 29.04 mo, respectively. Mean FIM score was 18.38 ± 1.06, mean modified Ashworth score was 43.5 ± 4.63, and mean Karnofsky score was 20. For the first 24 h, 5 of the patients experienced a subfebrile state, accompanied by mild headaches due to intrathecally administration and muscle pain because of intramuscularly administration. Neurological and functional examinations, laboratory tests, electroencephalography, and magnetic resonance imaging were performed to assess safety of treatment. Mean FIM score increased by 20.88 ± 3.31 in the first month (P = 0.027) and by 31.38 ± 14.69 in 12 mo (P = 0.012). The rate of patients with an FIM score of 126 increased from 14.58% to 16.57% in the first month and 24.90% in 12 mo.
Multiple triple-route Wharton’s jelly-derived MSC administrations were found to be safe for HIE patients, indicating neurological and functional improvement. Based on the findings obtained here, further randomized and placebo research could be performed.
Core Tip: Occurring due to the disruption of oxygen supply to the brain, hypoxic-ischemic encephalopathy is associated with substantial rates of morbidity and mortality. In addition to supportive therapy and symptomatic treatment, research on the treatment of hypoxic-ischemic encephalopathy has focused new therapautic strategies as stem cell therapy. This multi-center and open-label phase I study was performed to investigate the safety and preliminary efficacy of multiple triple-route Wharton’s Jelly-Derived Mesenchymal Stem Cells administrations. The patients included in this study also had improvement in modified Ashworth scores, Functional Independence Measure scores over the course of a year, indicating long-term impact on brain functions.