Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats.

Neural precursor cells (NSCs) hold great potential to treat a variety of neurodegenerative diseases and injuries to the spinal cord. However, current delivery techniques require an invasive approach in which an injection needle is advanced into the spinal parenchyma to deliver cells of interest. As such, this approach is associated with an inherent risk of spinal injury, as well as a limited delivery of cells into multiple spinal segments.

Feasibility of Human Neural Stem Cell Transplantation for the Treatment of Acute Subdural Hematoma in a Rat Model: A Pilot Study.

Human neural stem cells (hNSCs) transplantation in several brain injury models has established their therapeutic potential. However, the feasibility of hNSCs transplantation is still not clear for acute subdural hematoma (ASDH) brain injury that needs external decompression. Thus, the aim of this pilot study was to test feasibility using a rat ASDH decompression model with two clinically relevant transplantation methods.

Long-term Phase 1/2 intraspinal stem cell transplantation outcomes in ALS.

Objective: Intraspinal human spinal cord-derived neural stem cell (HSSC) transplantation is a potential therapy for amyotrophic lateral sclerosis (ALS); however, previous trials lack controls. This post hoc analysis compared ambulatory limb-onset ALS participants in Phase 1 and 2 (Ph1/2) open-label intraspinal HSSC transplantation studies up to 3 years after transplant to matched participants in Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) and ceftriaxone datasets to provide required analyses to inform future clinical trial designs.

Methods: Survival, ALSFRS-R, and a composite statistic (ALS/SURV) combining survival and ALS Functional Rating Scale revised (ALSFRS-R) functional status were assessed for matched participant subsets: PRO-ACT  = 1108, Ph1/2  = 21 and ceftriaxone  = 177, Ph1/2  = 20.

Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of phase 1 and 2 trials.

Objective: To test the safety of spinal cord transplantation of human stem cells in patients with amyotrophic lateral sclerosis (ALS) with escalating doses and expansion of the trial to multiple clinical centers.

Methods: This open-label trial included 15 participants at 3 academic centers divided into 5 treatment groups receiving increasing doses of stem cells by increasing numbers of cells/injection and increasing numbers of injections. All participants received bilateral injections into the cervical spinal cord (C3-C5).

Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-I: A Novel Cellular Therapy for Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder and a leading cause of dementia. Current treatment fails to modify underlying disease pathologies and very little progress has been made to develop effective drug treatments. Cellular therapies impact disease by multiple mechanisms, providing increased efficacy compared with traditional single-target approaches.

Pig models of neurodegenerative disorders: Utilization in cell replacement-based preclinical safety and efficacy studies.

An important component for successful translation of cell replacement-based therapies into clinical practice is the utilization of large animal models to conduct efficacy and/or safety cell dosing studies. Over the past few decades, several large animal models (dog, cat, nonhuman primate) were developed and employed in cell replacement studies; however, none of these models appears to provide a readily available platform to conduct effective and large-scale preclinical studies. In recent years, numerous pig models of neurodegenerative disorders were developed using both a transgenic approach as well as invasive surgical techniques.