Adult Neural Stem Cells from Midbrain Periventricular Regions Show Limited Neurogenic Potential after Transplantation into the Hippocampal Neurogenic Niche

Abstract

The regulation of adult neural stem or progenitor cell (aNSC) proliferation and differentiation as an interplay of cell-intrinsic and local environmental cues remains in part unclear, impeding their role in putative regenerative therapies. aNSCs with all major properties of NSCs in vitro have been identified in a variety of brain regions beyond the classic neurogenic niches, including the caudal periventricular regions (PVRs) of the midbrain, though active neurogenesis is either limited or merely absent in these regions. To elucidate cell-intrinsic properties of aNSCs from various PVRs, we here examined the proliferation and early differentiation capacity of murine aNSCs from non-neurogenic midbrain PVRs (PVRMB) compared to aNSCs from the neurogenic ventricular-subventricular zone (PVRV-SVZ) 7 days after transplantation into the permissive pro-neurogenic niche of the dentate gyrus (DG) of the hippocampus in mice. An initial in vitro characterization of the transplants displayed very similar characteristics of both aNSC grafts after in vitro expansion with equal capacities of terminal differentiation into astrocytes and Tuj1+ neurons. Upon the allogenic transplantation of the respective aNSCs into the DG, PVRMB grafts showed a significantly lower graft survival and proliferative capacity compared to PVRV-SVZ transplants, whereby the latter are exclusively capable of generating new neurons. Although these differences might be—in part—related to the transplantation procedure and the short-term study design, our data strongly imply important cell-intrinsic differences between aNSCs from neurogenic compared to non-neurogenic PVRs with respect to their neurogenic potential and/or their sensitivity to neurogenic cues.

Plant‐derived exosomes extracted from Lycium barbarum L. loaded with isoliquiritigenin to promote spinal cord injury repair based on 3D printed bionic scaffold

“…GFAP was chosen to identify the multidirectional differentiation ability of NSCs 50 . As a principal constituent of the axonal cytoskeleton, β III Tuj1 is widely used as a marker to distinguish neurons from other cell types 51 . Thus, a positive staining indicated that the cultured cells were NSCs.…”

The roles of neural stem cells in myelin regeneration and repair therapy after spinal cord injury

“…Later, Zhao and colleagues revealed that adult NSCs transplantation improved locomotor function in spinal cord transection rats, which associated with nerve regeneration and IGF-1R expression [ 85 ]. Recently, Fauser and colleagues successfully transplanted adult NSCs from midbrain periventricular regions into the hippocampal neurogenic niche [ 86 ]. Lv and colleagues evaluated the safety and efficacy of adult NSCs transplantation for cerebral palsy [ 87 ].…”

Ginsenoside Rg1 attenuates D‐galactose‐induced neural stem cell senescence via the Sirt1‐Nrf2‐BDNF pathway

“…With the progressive ageing of the global population, neurodegenerative diseases have emerged as a prominent contributor to compromised quality of life and increased mortality rates among the elderly (Cacabelos, 2017; Chang et al, 2021; Fereshtehnejad et al, 2019). It is due to the limited regenerative capacity of the adult nervous system and the death or irreversible dysfunction of the neural cells (Achilleos & Trainor, 2012; Fauser et al, 2021; Matsubara et al, 2021). Currently, the drugs approved by the Food and Drug Administration (FDA) such as MDA receptor antagonists, levodopa, and donepezil are used to prolong neurodegeneration by supplementing neurotransmitters and neurotrophic factors (Gao et al, 2022; Honorio et al, 2022; Nagai et al, 2022; Osmaniye et al, 2023; Rants'o et al, 2022; Safarpour et al, 2022).…”