Title:Comparative Outcomes of Intravenous, Intranasal, and Intracerebroventricular Transplantation of Human Neural Stem Cells
in Mice Model of Ischemic Stroke
Volume: 20
Issue: 2
Author(s): Mengze Zhang, Yaying Song, Chong Xie and Yangtai Guan*
Affiliation:
- Department of Neurology, Renji Hospital, School of Medicine Shanghai Jiaotong University, 160 Pujian Rd, Shanghai,
200127, P.R. China
Keywords:
Neural stem cells, ischemic stroke, delivery route, neurogenesis, glial scar, intravenous, intranasal, intracerebroventricular.
Abstract:
Background: Transplantation of neural stem cells improves ischemic stroke outcomes
in rodent models and is currently in the clinical test stage. However, the optimal delivery route to
achieve improved efficacy remains undetermined.
Objective: This study aims to evaluate three more clinically feasible delivery routes: intravenous
(IV), intranasal (IN), and intracerebroventricular (ICV). We compared the therapeutic efficacies
of the three routes of transplanting human neural stem cells (hNSCs) into mice with permanent
middle cerebral artery obstruction (pMCAO).
Methods: Behavioral tests and cresyl violet staining were used to evaluate the therapeutic efficacies
of functional recovery and lesion volumes. The expression of proinflammatory cytokines and
neurotrophic factors was measured by real-time PCR. The distribution and differentiation of hNSCs
were determined by immunofluorescence staining. The effect on endogenous neurogenesis
and astrocyte function were determined by immunofluorescence staining and western blot.
Results: hNSC transplantation using the three routes improved behavioral outcomes and reduced
lesion volumes; IV transplantation of hNSCs results in earlier efficacy and improves the inflammatory
microenvironment. The long-term distribution and differentiation of transplanted hNSCs in
the peri-infarct areas can only be evaluated using ICV delivery. IV and ICV transplantation of hNSCs
promote neurogenesis and modulate the dual function of astrocytes in the peri-infarct areas.
Conclusion: IV and IN delivery is suitable for repeated administration of hNSCs to achieve improved
prognosis. Comparatively, ICV transplantation provides long-term efficacy at lower doses
and fewer administration times.
