Human peripheral nerve-derived pluripotent cells can be stimulated by in vitro bone morphogenetic protein-2

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Authors
Sun, Renyi
Jia, Tanghong
Dart, Bradley
Shrestha, Sunaina
Bretches, Morgan
Heggeness, Michael H.
Yang, Shang-You
Advisors
Issue Date
2021-09-26
Type
Article
Keywords
Pluripotent stem cells , BMP-2 , Peripheral nerve , Human
Research Projects
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Citation
Sun, R., Jia, T., Dart, B., Shrestha, S., Bretches, M., Heggeness, M. H., & Yang, S. -. (2021). Human peripheral nerve-derived pluripotent cells can be stimulated by in vitro bone morphogenetic protein-2. Bioengineering, 8(10) doi:10.3390/bioengineering8100132
Abstract

We have recently identified a population of cells within the peripheral nerves of adult rodent animals (mice and rats) that can respond to Bone Morphogenetic Protein-2 (BMP-2) exposure or physical injury to rapidly proliferate. More importantly, these cells exhibited embryonic differentiation potentials that could be induced into osteoblastic and endothelial cells in vitro. The current study examined human nerve specimens to compare and characterize the cells after BMP-2 stimulation. Fresh pieces of human nerve tissue were minced and treated with either BMP-2 (750 ng/mL) or a PBS vehicle for 12 h at 37 °C, before being digested in 0.2% collagenase and 0.05% trypsin-EDTA. Isolated cells were cultured in a restrictive stem cell medium. Significantly more cells were obtained from the nerve pieces with the BMP-2 treatment in comparison with the PBS vehicle controls. Cell colonies started to form at Day 3. Expressions of the four transcription factors, namely, Klf4, c-Myc, Sox2, and Oct4, were confirmed at both the transcriptional and translational levels. The cells can be maintained in the stem cell culture medium for at least 6 weeks without changing their morphology. When the cells were transferred to a fibroblast growth medium, dispersed spindle-shaped motile cells were noted and became fibroblast activated protein-α (FAP) positive with immunocytochemistry staining. The data suggest that human peripheral nerve tissue also contains a population of cells that can respond to BMP-2 and express Klf4, Sox2, cMyc, and Oct4—the four transcription factors driving cell pluripotency. These cells are able to differentiate into FAP-positive fibroblasts. In summary, in human peripheral nerves also reside a population of quiescent cells with pluripotency potential that may be the same cells as rodent nerve-derived adult stem (NEDAPS) cells. It is proposed that these cells are possibly at the core of a previously unknown natural mechanism for healing an injury.

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Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Publisher
MDPI
Journal
Book Title
Series
Bioengineering;Vol. 8, Iss. 10
PubMed ID
DOI
ISSN
2306-5354
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