A nerve growth factor persistent delivery scaffold seeded with neurally differentiated bone marrow mesenchymal stem cells promoted the functional recovery of spinal cord injury in rats.

The objective was to design a scaffold that could continuously deliver nerve growth factor (NGF) combined with neurally differentiated bone marrow mesenchymal stem cells (BMSCs) to promote better recovery of spinal cord injury (SCI) in rats. BMSCs were induced to differentiate into neurons for 6 days in vitro, and then seeded on a NGF persistent delivery scaffold, both were transplanted to SCI rats in combination. Relevant extensive tests were conducted 1, 4 and 8 weeks after transplantation. The results showed that the scaffold had a stable ability to continuously release NGF and that the BMSCs on the scaffold could successfully differentiate into nerve cells. The results of Bacco, Beattie and Bresnahan (BBB) scores, inclined plane tests and electrophysiological investigations revealed that the rats in the combined regimen had better locomotor functional recovery. The results of H&E/Nissl staining, Golgi staining and immunofluorescence showed that the rats in the combined regimen retained the most neurons and had the least cavities and more formations of dendritic spines. Similarly, the positive rate was high for MAP2, NeuN and MBP, and low for GFAP. The graft of the NGF persistent delivery scaffold seeded with neurally differentiated BMSCs significantly reduced the formation of cavities and glial scars at the SCI sites and promoted neuronal survival, axonal regeneration and locomotor function recovery. Compared with the single graft of NGF persistent delivery scaffold or the single graft of neurally differentiated BMSCs, this combined scheme had a better effect in promoting the recovery of SCI.

[1]  Nageh K. Allam,et al.  Recent Advances in the Regenerative Approaches for Traumatic Spinal Cord Injury: Materials Perspective. , 2020, ACS biomaterials science & engineering.

[2]  Yihao Chen,et al.  A chitosan-based thermosensitive scaffold loaded with bone marrow-derived mesenchymal stem cells promotes motor function recovery in spinal cord injured mice , 2020, Biomedical materials.

[3]  Y. von Boxberg,et al.  Repair strategies for traumatic spinal cord injury, with special emphasis on novel biomaterial-based approaches. , 2020, Revue neurologique.

[4]  Yahong Zhao,et al.  Tubular scaffold with microchannels and an H‐shaped lumen loaded with bone marrow stromal cells promotes neuroregeneration and inhibits apoptosis after spinal cord injury , 2019, Journal of tissue engineering and regenerative medicine.

[5]  G. Perale,et al.  How can nanovectors be used to treat spinal cord injury? , 2019, Nanomedicine.

[6]  C. Angeli,et al.  Spinal Cord Epidural Stimulation for Lower Limb Motor Function Recovery in Individuals with Motor Complete Spinal Cord Injury. , 2019, Physical medicine and rehabilitation clinics of North America.

[7]  Wei Zhu,et al.  Biomimetic 3D-printed scaffolds for spinal cord injury repair , 2019, Nature Medicine.

[8]  Takahiro Shimizu,et al.  The effect of neutralization of nerve growth factor (NGF) on bladder and urethral dysfunction in mice with spinal cord injury , 2018, Neurourology and urodynamics.

[9]  E. Ling,et al.  Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury , 2018, Journal of biomedical materials research. Part A.

[10]  Š. Kubínová,et al.  Injectable hydroxyphenyl derivative of hyaluronic acid hydrogel modified with RGD as scaffold for spinal cord injury repair. , 2018, Journal of biomedical materials research. Part A.

[11]  Wei Li,et al.  Biodegradable Spheres Protect Traumatically Injured Spinal Cord by Alleviating the Glutamate‐Induced Excitotoxicity , 2018, Advanced materials.

[12]  J. Taxi,et al.  Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration. , 2017, Biomaterials.

[13]  Cunchuan Wang,et al.  A bridging SF/Alg composite scaffold loaded NGF for spinal cord injury repair. , 2017, Materials science & engineering. C, Materials for biological applications.

[14]  Brett J. Hilton,et al.  Cell transplantation therapy for spinal cord injury , 2017, Nature Neuroscience.

[15]  Xiaofeng Lian,et al.  Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury , 2017, Acta Pharmacologica Sinica.

[16]  Lars Olson,et al.  Rat models of spinal cord injury: from pathology to potential therapies , 2016, Disease Models & Mechanisms.

[17]  Sung-Rae Cho,et al.  Functional Recovery after the Transplantation of Neurally Differentiated Mesenchymal Stem Cells Derived from Bone Marrow in a Rat Model of Spinal Cord Injury , 2016, Cell transplantation.

[18]  M. Tuszynski,et al.  Bone Marrow Stromal Cell Intraspinal Transplants Fail to Improve Motor Outcomes in a Severe Model of Spinal Cord Injury. , 2016, Journal of neurotrauma.

[19]  S. Malik,et al.  Autologous mesenchymal stromal cell transplantation for spinal cord injury: A Phase I pilot study. , 2016, Cytotherapy.

[20]  Shu Liu,et al.  Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury. , 2016, Biomaterials.

[21]  S. Jeon,et al.  A Phase III Clinical Trial Showing Limited Efficacy of Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury. , 2016, Neurosurgery.

[22]  Lei Tao,et al.  An Injectable, Self‐Healing Hydrogel to Repair the Central Nervous System , 2015, Advanced materials.

[23]  Michael G Fehlings,et al.  Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. , 2008, Neurosurgical focus.

[24]  L. Weaver,et al.  NGF mRNA is expressed in the dorsal root ganglia after spinal cord injury in the rat , 2007, Experimental Neurology.

[25]  J. Fawcett.  Overcoming inhibition in the damaged spinal cord. , 2006, Journal of neurotrauma.

[26]  Adam R Ferguson,et al.  A simple post hoc transformation that improves the metric properties of the BBB scale for rats with moderate to severe spinal cord injury. , 2004, Journal of neurotrauma.

[27]  M. Fehlings,et al.  Epidemiology, demographics, and pathophysiology of acute spinal cord injury. , 2001, Spine.

[28]  A. Harvey,et al.  Neurotrophic Factors Used to Treat Spinal Cord Injury. , 2017, Vitamins and hormones.

[29]  H. Wong,et al.  Using NGF heparin-poloxamer thermosensitive hydrogels to enhance the nerve regeneration for spinal cord injury. , 2016, Acta biomaterialia.