The Potential for Cellular Therapy Combined with Growth Factors in Spinal Cord Injury

Rosner, Jack; Avalos, Pablo; Acosta, Frank L.; Liu, John; Drazin, Doniel

doi:10.1155/2012/826754

Cited by 27 publications

(20 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although QL6 nanofibers themselves might improve cell survival 4,15 , nevertheless, the use of growth factors seems to be advantageous 16,17,18,19,20,21 . They can be administered either by hydrogels releasing growth factors 22 , or by application via osmotic pumps (as described above).…”

Section: Discussionmentioning

confidence: 99%

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury

Zweckberger

Liu

Wang

et al. 2015

JoVE

View full text Add to dashboard Cite

Spinal cord injuries (SCI) cause serious neurological impairment and psychological, economic, and social consequences for patients and their families. Clinically, more than 50% of SCI affect the cervical spine 1 . As a consequence of the primary injury, a cascade of secondary mechanisms including inflammation, apoptosis, and demyelination occur finally leading to tissue scarring and development of intramedullary cavities 2,3 . Both represent physical and chemical barriers to cell transplantation, integration, and regeneration. Therefore, shaping the inhibitory environment and bridging cavities to create a supportive milieu for cell transplantation and regeneration is a promising therapeutic target 4 . Here, a contusion/ compression model of cervical SCI using an aneurysm clip is described. This model is more clinically relevant than other experimental models, since complete transection or ruptures of the cord are rare. Also in comparison to the weight drop model, which in particular damage the dorsum columns, circumferential compression of the spinal cord appears advantageous. Clip closing force and duration can be adjusted to achieve different injury severity. A ring spring facilitates precise calibration and constancy of clip force. Under physiological conditions, synthetic selfassembling peptides (SAP) self-assemble into nanofibers and thus, are appealing for application in SCI 5 . They can be injected directly into the lesion minimizing damage to the cord. SAPs are biocompatible structures erecting scaffolds to bridge intramedullary cavities and thus, equip the damaged cord for regenerative treatments. K2(QL)6K2 (QL6) is a novel SAP introduced by Dong et al. 6 In comparison to other peptides, QL6self-assembles into β-sheets at neutral pH 6 .14 days after SCI, after the acute stage, SAPs are injected into the center of the lesion and neural precursor cells (NPC) are injected into adjacent dorsal columns. In order to support cell survival, transplantation is combined with continuous subdural administration of growth factors by osmotic micro pumps for 7 days. Video LinkThe video component of this article can be found at

show abstract

Section: Discussionmentioning

confidence: 99%

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury

Zweckberger

Liu

Wang

et al. 2015

JoVE

View full text Add to dashboard Cite

show abstract

“…Our future studies will be aimed at investigating a combinatorial effect of SCs and OECs with selected growth factors (e.g., bFGF) in transplantation to promote cell migration, axon regeneration, and functional recovery in SCI. This purpose is strengthened by Rosner and colleagues (), who highlighted the importance of cellular therapy combined with some growth factors to create a neuroprotective environment in SCI.…”

Section: Discussionmentioning

confidence: 99%

Viability of olfactory ensheathing cells after hypoxia and serum deprivation: Implication for therapeutic transplantation

Pellitteri

Catania

Bonaccorso

et al. 2014

J of Neuroscience Research

View full text Add to dashboard Cite

Olfactory ensheathing cells (OECs) represent glial cells supporting neuronal turnover in the olfactory system. In vitro, OECs promote axonal growth as a source of neurotrophic growth factors; in vivo, they produce myelin, promoting remyelination of damaged axons. Consequently, OEC transplantation appears to be a promising treatment for spinal cord injury, although the functional recovery is limited. This might be ascribed to the microenvironment at the lesion site, lacking growth factors (GFs), nutrients, and oxygen. To mimic this condition, we used an in vitro approach by growing primary neonatal mouse OECs under hypoxic conditions and/or serum deprivation. In addition, we compared OECs survival/proliferation with that of primary cultures of Schwann cells (SCs) and astrocytes under the same experimental conditions. Cultures were analyzed by immunocytochemistry, and cell viability was evaluated by MTT assay. Different GFs, such as NGF, bFGF, and GDNF, and their combination were used to rescue cells from serum and/or oxygen deprivation. We show that the cell types were differently sensitive to the tested stress conditions and that OECs were the most sensitive among them. Moreover, OEC viability was rescued by bFGF under serum-deprived or hypoxic condition but not under conditions of drastic serum deprivation and hypoxia. bFGF was effective also for the other cell types, whereas the effect of the other GFs was negligible. This model suggests that administration of bFGF might be considered useful to sustain cell survival/proliferation after transplantation of OECs either alone or in combination with other glial cell types.

show abstract

“…Spinal cord injury (SCI) is a major health issue which causes profound changes in almost all physical systems and functional abilities. It may cause symptoms ranging from pain to complete loss of motor and sensory functions below the level of injury . The estimated annual global incidence of SCI is 40–80 cases per million population.…”

Section: Introductionmentioning

confidence: 99%

A novel method for constructing an acellular 3D biomatrix from bovine spinal cord for neural tissue engineering applications

Arslan

Efe

Arslan

2019

Biotechnology Progress

View full text Add to dashboard Cite

In this study, we aimed at generating 3‐dimensional (3D) decellularized bovine spinal cord extracellular matrix‐based scaffolds (3D‐dCBS) for neural tissue engineering applications. Within this scope, bovine spinal cord tissue pieces were homogenized in 0.1 M NaOH and this viscous mixture was molded to attain 3D bioscaffolds. After resultant bioscaffolds were chemically crosslinked, the decellularization process was conducted with detergent, buffer, and enzyme solutions. Nuclear remnants in the native tissue and 3D‐dCBS were determined with DNA content analysis and agarose gel electrophoresis. Afterward, 3D‐dCBS were biochemically characterized in depth via glycosaminoglycan (GAG) content, hydroxyproline (HYP) assay, and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE). Cellular survival of human adipose‐derived mesenchymal stem cells (hAMSCs) on the 3D‐dCBS for 3rd, 7th, and 10th days was assessed via MTT assay. Scaffold and cell/scaffold constructs were also evaluated with scanning electron microscopy and histochemical studies. DNA contents for native and 3D‐dCBS were respectively found to be 520.76 ± 18.11 and 28.80 ± 0.20 ng/mg dry weight (n = 3), indicating a successful decellularization process. GAG content, HYP assay, and SDS‐PAGE results proved that the extracellular matrix was substantially preserved during the decellularization process. In conclusion, it is believed that the novel decellularization method may allow fabricating 3D bioscaffolds with desired geometry from soft nervous system tissues.

show abstract

The Potential for Cellular Therapy Combined with Growth Factors in Spinal Cord Injury

Cited by 27 publications

References 122 publications

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury

Viability of olfactory ensheathing cells after hypoxia and serum deprivation: Implication for therapeutic transplantation

A novel method for constructing an acellular 3D biomatrix from bovine spinal cord for neural tissue engineering applications

Contact Info

Product

Resources

About