Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells
Damage to the nervous system can cause devastating diseases or musculoskeletal dysfunctions and transplantation of progenitor stem cells can be an excellent treatment option in this regard. Preclinical studies demonstrate that untreated stem cells, unlike stem cells activated to differentiate into...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/1035374 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832559393159249920 |
|---|---|
| author | Vedavathi Madhu Abhijit S. Dighe Quanjun Cui D. Nicole Deal |
| author_facet | Vedavathi Madhu Abhijit S. Dighe Quanjun Cui D. Nicole Deal |
| author_sort | Vedavathi Madhu |
| collection | DOAJ |
| description | Damage to the nervous system can cause devastating diseases or musculoskeletal dysfunctions and transplantation of progenitor stem cells can be an excellent treatment option in this regard. Preclinical studies demonstrate that untreated stem cells, unlike stem cells activated to differentiate into neuronal lineage, do not survive in the neuronal tissues. Conventional methods of inducing neuronal differentiation of stem cells are complex and expensive. We therefore sought to determine if a simple, one-step, and cost effective method, previously reported to induce neuronal differentiation of embryonic stem cells and induced-pluripotent stem cells, can be applied to adult stem cells. Indeed, dual inhibition of activin/nodal/TGF-β and BMP pathways using SB431542 and dorsomorphin, respectively, induced neuronal differentiation of human adipose derived stem cells (hADSCs) as evidenced by formation of neurite extensions, protein expression of neuron-specific gamma enolase, and mRNA expression of neuron-specific transcription factors Sox1 and Pax6 and matured neuronal marker NF200. This process correlated with enhanced phosphorylation of p38, Erk1/2, PI3K, and Akt1/3. Additionally, in vitro subcutaneous implants of SB431542 and dorsomorphin treated hADSCs displayed significantly higher expression of active-axonal-growth-specific marker GAP43. Our data offers novel insights into cell-based therapies for the nervous system repair. |
| format | Article |
| id | doaj-art-03048d699c6d445ca2d149150c7cd554 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-03048d699c6d445ca2d149150c7cd5542025-02-03T01:30:00ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/10353741035374Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem CellsVedavathi Madhu0Abhijit S. Dighe1Quanjun Cui2D. Nicole Deal3Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA 22908, USAOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA 22908, USAOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA 22908, USAOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA 22908, USADamage to the nervous system can cause devastating diseases or musculoskeletal dysfunctions and transplantation of progenitor stem cells can be an excellent treatment option in this regard. Preclinical studies demonstrate that untreated stem cells, unlike stem cells activated to differentiate into neuronal lineage, do not survive in the neuronal tissues. Conventional methods of inducing neuronal differentiation of stem cells are complex and expensive. We therefore sought to determine if a simple, one-step, and cost effective method, previously reported to induce neuronal differentiation of embryonic stem cells and induced-pluripotent stem cells, can be applied to adult stem cells. Indeed, dual inhibition of activin/nodal/TGF-β and BMP pathways using SB431542 and dorsomorphin, respectively, induced neuronal differentiation of human adipose derived stem cells (hADSCs) as evidenced by formation of neurite extensions, protein expression of neuron-specific gamma enolase, and mRNA expression of neuron-specific transcription factors Sox1 and Pax6 and matured neuronal marker NF200. This process correlated with enhanced phosphorylation of p38, Erk1/2, PI3K, and Akt1/3. Additionally, in vitro subcutaneous implants of SB431542 and dorsomorphin treated hADSCs displayed significantly higher expression of active-axonal-growth-specific marker GAP43. Our data offers novel insights into cell-based therapies for the nervous system repair.http://dx.doi.org/10.1155/2016/1035374 |
| spellingShingle | Vedavathi Madhu Abhijit S. Dighe Quanjun Cui D. Nicole Deal Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells Stem Cells International |
| title | Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells |
| title_full | Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells |
| title_fullStr | Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells |
| title_full_unstemmed | Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells |
| title_short | Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells |
| title_sort | dual inhibition of activin nodal tgf β and bmp signaling pathways by sb431542 and dorsomorphin induces neuronal differentiation of human adipose derived stem cells |
| url | http://dx.doi.org/10.1155/2016/1035374 |
| work_keys_str_mv | AT vedavathimadhu dualinhibitionofactivinnodaltgfbandbmpsignalingpathwaysbysb431542anddorsomorphininducesneuronaldifferentiationofhumanadiposederivedstemcells AT abhijitsdighe dualinhibitionofactivinnodaltgfbandbmpsignalingpathwaysbysb431542anddorsomorphininducesneuronaldifferentiationofhumanadiposederivedstemcells AT quanjuncui dualinhibitionofactivinnodaltgfbandbmpsignalingpathwaysbysb431542anddorsomorphininducesneuronaldifferentiationofhumanadiposederivedstemcells AT dnicoledeal dualinhibitionofactivinnodaltgfbandbmpsignalingpathwaysbysb431542anddorsomorphininducesneuronaldifferentiationofhumanadiposederivedstemcells |