Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection
Spinal cord injury (SCI), involving damaged axons and glial scar tissue, often culminates in irreversible impairments. Achieving substantial recovery following complete spinal cord transection remains an unmet challenge. Here, we report of implantation of an engineered 3D construct embedded with hum...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-10-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fnins.2017.00589/full |
| _version_ | 1818131042387623936 |
|---|---|
| author | Javier Ganz Erez Shor Shaowei Guo Anton Sheinin Ina Arie Izhak Michaelevski Izhak Michaelevski Sandu Pitaru Daniel Offen Shulamit Levenberg |
| author_facet | Javier Ganz Erez Shor Shaowei Guo Anton Sheinin Ina Arie Izhak Michaelevski Izhak Michaelevski Sandu Pitaru Daniel Offen Shulamit Levenberg |
| author_sort | Javier Ganz |
| collection | DOAJ |
| description | Spinal cord injury (SCI), involving damaged axons and glial scar tissue, often culminates in irreversible impairments. Achieving substantial recovery following complete spinal cord transection remains an unmet challenge. Here, we report of implantation of an engineered 3D construct embedded with human oral mucosa stem cells (hOMSC) induced to secrete neuroprotective, immunomodulatory, and axonal elongation-associated factors, in a complete spinal cord transection rat model. Rats implanted with induced tissue engineering constructs regained fine motor control, coordination and walking pattern in sharp contrast to the untreated group that remained paralyzed (42 vs. 0%). Immunofluorescence, CLARITY, MRI, and electrophysiological assessments demonstrated a reconnection bridging the injured area, as well as presence of increased number of myelinated axons, neural precursors, and reduced glial scar tissue in recovered animals treated with the induced cell-embedded constructs. Finally, this construct is made of bio-compatible, clinically approved materials and utilizes a safe and easily extractable cell population. The results warrant further research with regards to the effectiveness of this treatment in addressing spinal cord injury. |
| first_indexed | 2024-12-11T08:14:38Z |
| format | Article |
| id | doaj.art-592ec32337884285b7a5e5ff53dcd11a |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-11T08:14:38Z |
| publishDate | 2017-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-592ec32337884285b7a5e5ff53dcd11a2022-12-22T01:14:48ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2017-10-011110.3389/fnins.2017.00589289724Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord TransectionJavier Ganz0Erez Shor1Shaowei Guo2Anton Sheinin3Ina Arie4Izhak Michaelevski5Izhak Michaelevski6Sandu Pitaru7Daniel Offen8Shulamit Levenberg9Department of Human Molecular Genetics and Biochemistry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Biomedical Engineering, Technion, Haifa, IsraelDepartment of Biomedical Engineering, Technion, Haifa, IsraelDepartment of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelDepartment of Oral Biology, School of Dental Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelDepartment of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel, IsraelDepartment of Oral Biology, School of Dental Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Human Molecular Genetics and Biochemistry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Biomedical Engineering, Technion, Haifa, IsraelSpinal cord injury (SCI), involving damaged axons and glial scar tissue, often culminates in irreversible impairments. Achieving substantial recovery following complete spinal cord transection remains an unmet challenge. Here, we report of implantation of an engineered 3D construct embedded with human oral mucosa stem cells (hOMSC) induced to secrete neuroprotective, immunomodulatory, and axonal elongation-associated factors, in a complete spinal cord transection rat model. Rats implanted with induced tissue engineering constructs regained fine motor control, coordination and walking pattern in sharp contrast to the untreated group that remained paralyzed (42 vs. 0%). Immunofluorescence, CLARITY, MRI, and electrophysiological assessments demonstrated a reconnection bridging the injured area, as well as presence of increased number of myelinated axons, neural precursors, and reduced glial scar tissue in recovered animals treated with the induced cell-embedded constructs. Finally, this construct is made of bio-compatible, clinically approved materials and utilizes a safe and easily extractable cell population. The results warrant further research with regards to the effectiveness of this treatment in addressing spinal cord injury.http://journal.frontiersin.org/article/10.3389/fnins.2017.00589/fullspinal cord injuryoral mucosastem cellstissue engineeringregenerative medicine |
| spellingShingle | Javier Ganz Erez Shor Shaowei Guo Anton Sheinin Ina Arie Izhak Michaelevski Izhak Michaelevski Sandu Pitaru Daniel Offen Shulamit Levenberg Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection Frontiers in Neuroscience spinal cord injury oral mucosa stem cells tissue engineering regenerative medicine |
| title | Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection |
| title_full | Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection |
| title_fullStr | Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection |
| title_full_unstemmed | Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection |
| title_short | Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection |
| title_sort | implantation of 3d constructs embedded with oral mucosa derived cells induces functional recovery in rats with complete spinal cord transection |
| topic | spinal cord injury oral mucosa stem cells tissue engineering regenerative medicine |
| url | http://journal.frontiersin.org/article/10.3389/fnins.2017.00589/full |
| work_keys_str_mv | AT javierganz implantationof3dconstructsembeddedwithoralmucosaderivedcellsinducesfunctionalrecoveryinratswithcompletespinalcordtransection AT erezshor implantationof3dconstructsembeddedwithoralmucosaderivedcellsinducesfunctionalrecoveryinratswithcompletespinalcordtransection AT shaoweiguo implantationof3dconstructsembeddedwithoralmucosaderivedcellsinducesfunctionalrecoveryinratswithcompletespinalcordtransection AT antonsheinin implantationof3dconstructsembeddedwithoralmucosaderivedcellsinducesfunctionalrecoveryinratswithcompletespinalcordtransection AT inaarie implantationof3dconstructsembeddedwithoralmucosaderivedcellsinducesfunctionalrecoveryinratswithcompletespinalcordtransection AT izhakmichaelevski implantationof3dconstructsembeddedwithoralmucosaderivedcellsinducesfunctionalrecoveryinratswithcompletespinalcordtransection AT izhakmichaelevski implantationof3dconstructsembeddedwithoralmucosaderivedcellsinducesfunctionalrecoveryinratswithcompletespinalcordtransection AT sandupitaru implantationof3dconstructsembeddedwithoralmucosaderivedcellsinducesfunctionalrecoveryinratswithcompletespinalcordtransection AT danieloffen implantationof3dconstructsembeddedwithoralmucosaderivedcellsinducesfunctionalrecoveryinratswithcompletespinalcordtransection AT shulamitlevenberg implantationof3dconstructsembeddedwithoralmucosaderivedcellsinducesfunctionalrecoveryinratswithcompletespinalcordtransection |