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Review
. 2024 Jan 12;25(2):993.
doi: 10.3390/ijms25020993.

Harnessing the Stem Cell Niche in Regenerative Medicine: Innovative Avenue to Combat Neurodegenerative Diseases

Gordana Velikic  1   2 , Dusan M Maric  1   3 , Dusica L Maric  4 , Gordana Supic  5   6 , Miljan Puletic  3 , Oliver Dulic  7 , Danilo Vojvodic  5   6
Affiliations
Review

Harnessing the Stem Cell Niche in Regenerative Medicine: Innovative Avenue to Combat Neurodegenerative Diseases

Gordana Velikic et al. Int J Mol Sci. .

Abstract

Regenerative medicine harnesses the body's innate capacity for self-repair to restore malfunctioning tissues and organs. Stem cell therapies represent a key regenerative strategy, but to effectively harness their potential necessitates a nuanced understanding of the stem cell niche. This specialized microenvironment regulates critical stem cell behaviors including quiescence, activation, differentiation, and homing. Emerging research reveals that dysfunction within endogenous neural stem cell niches contributes to neurodegenerative pathologies and impedes regeneration. Strategies such as modifying signaling pathways, or epigenetic interventions to restore niche homeostasis and signaling, hold promise for revitalizing neurogenesis and neural repair in diseases like Alzheimer's and Parkinson's. Comparative studies of highly regenerative species provide evolutionary clues into niche-mediated renewal mechanisms. Leveraging endogenous bioelectric cues and crosstalk between gut, brain, and vascular niches further illuminates promising therapeutic opportunities. Emerging techniques like single-cell transcriptomics, organoids, microfluidics, artificial intelligence, in silico modeling, and transdifferentiation will continue to unravel niche complexity. By providing a comprehensive synthesis integrating diverse views on niche components, developmental transitions, and dynamics, this review unveils new layers of complexity integral to niche behavior and function, which unveil novel prospects to modulate niche function and provide revolutionary treatments for neurodegenerative diseases.

Keywords: Alzheimer’s disease; Parkinson’s disease; artificial intelligence; morphogenetic fields; neurodegenerative diseases; neurogenesis; organoids; self-regeneration; stem cell niche; tumorigenesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 2
Figure 2
Key elements of the niche. The upper and lower plots in the middle depict healthy and diseased niches, respectively. The legend strip at the bottom illustrates the stages of the elements included in the middle plots. The text boxes on the sides list fundamental elements and the importance and challenge of the niches’ elements’ research and deployments.
Figure 1
Figure 1
Mechanisms behind the stemness of the niche. For the sake of simplicity, the arrows show basic signaling pathways that influence different stemness functions. See Figure 2 for icon details.
Figure 3
Figure 3
Basic elements of niche’s multidimensional landscape.
Figure 4
Figure 4
Sex-specific stem cell niches: understanding the unique biological mechanisms in men (XY) and women (XX) for enhanced neurodegenerative disease therapy.
Figure 5
Figure 5
Niche-based deployment.
See this image and copyright information in PMC

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