Implanted Adult Human Dental Pulp Stem Cells Induce Endogenous Axon Guidance

TLDR

The human central nervous system has limited regenerative capacity, but stem cell therapies may overcome this through neural replacement or secreted factors that alter host tissue. The study hypothesizes that implanted dental pulp stem cells secrete factors that guide axons in a receptive host nervous system. The authors transplanted human dental pulp stem cells into an avian embryonic model and found that axons were chemoattracted to the grafts via CXCL12/CXCR4 signaling. The study provides first direct evidence that DPSCs can induce neuroplasticity in a receptive host nervous system. Potential conflicts of interest are disclosed at the end of the article.

Abstract

Abstract The human central nervous system has limited capacity for regeneration. Stem cell-based therapies may overcome this through cellular mechanisms of neural replacement and/or through molecular mechanisms, whereby secreted factors induce change in the host tissue. To investigate these mechanisms, we used a readily accessible human cell population, dental pulp progenitor/stem cells (DPSCs) that can differentiate into functionally active neurons given the appropriate environmental cues. We hypothesized that implanted DPSCs secrete factors that coordinate axon guidance within a receptive host nervous system. An avian embryonic model system was adapted to investigate axon guidance in vivo after transplantation of adult human DPSCs. Chemoattraction of avian trigeminal ganglion axons toward implanted DPSCs was mediated via the chemokine, CXCL12, also known as stromal cell-derived factor-1, and its receptor, CXCR4. These findings provide the first direct evidence that DPSCs may induce neuroplasticity within a receptive host nervous system. Disclosure of potential conflicts of interest is found at the end of this article.