Tracking Induced Pluripotent Stem Cells–Derived Neural Stem Cells in the Central Nervous System of Rats and Monkeys

Abstract

Despite of the immense breakthroughs of induced pluripotent stem cells (iPSCs), clinical application of iPSCs and their derivates remains hampered by a lack of definitive in vivo studies. Here, we attempted to track iPSCsderived neural stem cells (NSCs) in the rodent and primate central nervous system (CNS) and explore their therapeutic viability for stem cell replacement in traumatic brain injury (TBI) rats and monkeys with spinal cord injury (SCI). Superparamagnetic iron oxide (SPIO) particles were used to label iPSCs-derived NSCs in vitro. Labeled NSCs were implanted into TBI rats and SCI monkeys 1 week after injury, and then imaged using gradient reflection echo (GRE) sequence by 3.0T magnetic resonance imaging (MRI) scanner. MRI analysis was performed at 1, 7, 14, 21, and 30 days, respectively, following cell transplantation. Pronounced hypointense signals were initially detected at the cell injection sites in rats and monkeys and were later found to extend progressively to the lesion regions, demonstrating that iPSCs-derived NSCs could migrate to the lesion area from the primary sites. The therapeutic efficacy of iPSCs-derived NSCs was examined concomitantly through functional recovery tests of the animals. In this study, we tracked iPSCs-derived NSCs migration in the CNS of TBI rats and SCI monkeys in vivo for the first time. Functional recovery tests showed obvious motor function improvement in transplanted animals. These data provide the necessary foundation for future clinical application of iPSCs for CNS injury.

The effect of magnetic nanoparticles on neuronal differentiation of induced pluripotent stem cell-derived neural precursors

“…45 Similarly, in iPSC-derived neural stem cells, labeling of cells with various contrast agents did not affect the differentiation potential into various types of neural precursor cells. 46 Our results from qRT-PCR analysis showed that the early neural marker nestin was downregulated and neuronal markers (β-III-tubulin and synaptophysin) were upregulated during the differentiation of iPSC-NPs.…”

Induced pluripotent stem cells: An update

“…The studies from this finding provide the necessary foundation for future clinical application of iPSCs for CNS injury [28].…”

iPS Cell Transplantation for Traumatic Spinal Cord Injury

“…Tang and colleagues transplanted human iPS cell-derived NSCs labelled in vitro with superparamagnetic iron oxide particles into both a rat model of traumatic brain injury and a monkey model of SCI at 1 week post-injury. Using recurrent in vivo magnetic resonance imaging (MRI) tracking until 30 days post-injury, the authors showed that transplant-derived cells could progressively migrate from injection sites, which was accompanied by significant motor function recovery [56]. Despite the graft integration shown in these studies, it has yet to be mechanistically determined how these cells are promoting therapeutic effects.…”