Discussion
infection, bleeding, nerve injury, intravascular infusion
CEREBROSPINAL FLUID LEAKAGE, INFECTION, BLEEDING, SECONDARY
This study is a randomized controlled clinical trial with a small sample size and evaluates the safety and efficacy of intranasal delivery of NSCs composite patches for the treatment of CP. No severe AEs associated with NSCs treatment were observed throughout the treatment duration and follow-up. The clinical assessment of scales showed that NSCs intranasal administration could improve the gross motor, fine motor, self-care ability, expressive ability, social skills, and sleep quality of CP patients. The data from EEG and MRI provide evidence for brain functional and structural improvements after NSCs treatment.The most suitable administration route of stem cells is still unknown. Intrathecal administration and intravenous/intraarterial injection are the most commonly used delivery strategies for stem cell therapy in CP. Many AEs (such as bleeding at the puncture site, infection, and cerebrospinal fluid leakage) caused by the intrathecal injection may reduce the surgical tolerance of CP children and the secondary injury introduced by the transplantation method neutralizes part of the effects mediated by stem cells. During intravascular infusion, stem cells tend to accumulate in organs with rich capillary networks owing to the large volume [Meanwhile, the limitation of BBB makes it difficult for stem cells to enter the central nervous system through intravascular infusion, reducing the utilization rate of stem cells [The detection of FBN is helpful in measuring the recovery of brain function. We all know that the normal operation of brain networks requires neuronal activity with plasticity and stability [Another manifestation of recovery from nerve injury is morphological reconstruction [This study is the first attempt at nasal administration of stem cells in the human body, which provides a reference basis for future nasal transplantation of stem cells. At the same time, we first introduced the FBN analysis based on graph theory to evaluate brain function changes after stem cell therapy in terms of sleep EEG, which provides objective evidence for assessing of the efficacy of stem cell therapy. There were also some limitations exist for this study. First, the open-label design might be a possible limitation for this explorative study. But it is unlikely to affect AEs detection and efficacy assessment as intranasal administration is a minimally invasive operation and the efficacy assessment was regulated to be conducted by independent physicians other than the treating physician. Second, further study should include a placebo-controlled group based on a large-scale double-blinded, randomized controlled trial. Third, extending the follow-up time to obtain long-term safety and efficacy data. Finally, using stem cell tracers and other imaging data, such as magnetic resonance spectroscopy, can help better understand the potential mechanism of stem cells in neuronal repair.