scholarly journals Human Peripheral Nerve-Derived Pluripotent Cells Can Be Stimulated by In Vitro Bone Morphogenetic Protein-2

2021 ◽  
Vol 8 (10) ◽  
pp. 132
Author(s):  
Renyi Sun ◽  
Tanghong Jia ◽  
Bradley Dart ◽  
Sunaina Shrestha ◽  
Morgan Bretches ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Peripheral Nerve ◽  
Bone Morphogenetic Protein ◽  
Peripheral Nerves ◽  
Bone Morphogenetic Protein 2 ◽  
Nerve Tissue ◽  
Morphogenetic Protein ◽  
Human Nerve

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.

scholarly journals Pluripotent Stem Cells Can Be Isolated from Human Peripheral Nerves after in vitro BMP-2 Stimulation

2019 ◽  
Author(s):  
Ren-Yi Sun ◽  
Michael H. Heggeness ◽  
Tanghong Jia ◽  
Sunaina Shrestha ◽  
Bradley Dart ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Peripheral Nerves ◽  
Nerve Tissue ◽  
Isolated Cells ◽  
Adult Mice ◽  
Stem Cell Medium ◽  
Natural Mechanism ◽  
Human Nerve

AbstractWe have recently identified a population of cells within the peripheral nerves of adult mice that can respond to 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 (750ng/ml) or vehicle for 12 hours at 37°C, before digested in 0.2% collagenase and 0.05% trypsin-EDTA. Isolated cells were cultured in restrictive stem cell medium. Significantly more cells were obtained from the nerve pieces with BMP-2 treatment in comparison with the non-treated controls. Cell colonies were starting to form at day 3. Expressions of the 4 transcription factors Klf4, c-Myc, Sox2 and Oct4 were confirmed at both transcriptional and translational levels. The cells can be maintained in the stem cell culture medium for at least 6 weeks without changing morphologies. When the cells were switched to fibroblast growth medium, dispersed spindle-shaped cells were noted and became fibroblast activated protein-α (FAP) positive following immunocytochemistry staining. The data suggested that human peripheral nerve tissue also contain a population of cells that can respond to BMP-2 and express all four transcription factors KLF4, Sox2, cMyc, and Oct4. These cells are capable to differentiate into FAP-positive fibroblasts. It is proposed that these cells are possibly at the core of a previously unknown natural mechanism for healing injury.

The Effect of Bone Morphogenetic Protein-2 on Rat Intervertebral Disc Cells in Vitro

Spine ◽  
2003 ◽  
Vol 28 (16) ◽  
pp. 1773-1780 ◽  
Author(s):  
S. Tim Yoon ◽  
Keun Su Kim ◽  
Jun Li ◽  
Jin Soo Park ◽  
Tomoyuki Akamaru ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Disc Cells

Bone morphogenetic protein 2 controls steroid-induced osteonecrosis of the femoral head via directly inhibiting interleukin-34 expression

2021 ◽  
Author(s):  
Meng Wang ◽  
Hong Sung Min ◽  
Haojie Shan ◽  
Yiwei Lin ◽  
Wenyang Xia ◽  
...  
Keyword(s):  
Femoral Head ◽  
Bone Morphogenetic Protein ◽  
Inflammatory Responses ◽  
Gene Knockout ◽  
Osteoclast Differentiation ◽  
Bone Morphogenetic Protein 2 ◽  
Qrt Pcr ◽  
Morphogenetic Protein ◽  
Local Expression

Increased inflammatory responses is one of the major characteristics of osteonecrosis of the femoral head (ONFH). We aimed to investigate the function of bone morphogenetic protein 2 (BMP-2)/interleukin (IL)-34 axis in the inflammatory responses of ONFH. The systemic and local expression of BMPs in ONFH patients were detected by qRT-PCR and ELISA. In vitro osteoclast differentiation and ONFH mouse models, induced by 20 mg/kg methylprednisolone through intramuscular injection, were established using wild type and BMP-2-/- mice to explore the regulatory role of BMP-2 in pro-inflammatory responses and bone defects of ONFH. IL-34 expression and function were examined in vitro and in vivo through qRT-PCR, TRAP staining, and gene knockout. The systemic and local expression of BMPs were elevated in ONFH patients. BMP-2 reduced the production of pro-inflammatory cytokines and inhibited the differentiation of osteoclasts. Mechanistically, BMP-2 inhibited osteoclasts formation through suppressing IL-34 expression, and then promoted bone repair and alleviated ONFH. In conclusion, our study reveals that BMP-2 inhibits inflammatory responses and osteoclast formation through down-regulating IL-34.

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