Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord Injury

Abstract

Cervical spinal cord trauma represents more than half of the spinal cord injury (SCI) cases worldwide. Respiratory compromise, as well as severe limb motor deficits, are among the main consequences of cervical lesions. In the present work, a Gellan Gum (GG)-based hydrogel modified with GRGDS peptide, together with adipose tissuederived stem/stromal cells (ASCs) and olfactory ensheathing cells (OECs), was used as a therapeutic strategy after a C2 hemisection SCI in rats. Hydrogel or cells alone, and a group without treatment, were also tested. Four weeks after injury, compound muscle action potentials (CMAPs) were performed to assess functional phrenic motor neuron (PhMN) innervation of the diaphragm; no differences were observed amongst groups, confirming that the PhMN pool located between C3 and C5 was not affected by the C2 injury or by the treatments. In the same line, the vast majority of diaphragmatic neuromuscular junctions remained intact. Five weeks post-injury, inspiratory bursting of the affected ipsilateral hemidiaphragm was evaluated through EMG recordings of dorsal, medial and ventral subregions of the muscle. All treatments significantly increased EMG amplitude at the ventral portion in comparison to untreated animals, but only the combinatorial group presented increased EMG amplitude at the medial portion of the hemidiaphragm. No differences were observed in forelimb motor function, neither in markers for axonal regrowth (neuronal tracers), astrogliosis (GFAP) and inflammatory cells (CD68). Moreover, using Von Frey testing of mechanical allodynia, it was possible to find a significant effect of the group combining hydrogel and cells on hypersensitivity; rats with a SCI displayed an increased response of the contralateral forelimb to a normally innocuous mechanical stimulus, but after treatment with the combinatorial therapy this behavior was reverted almost to the levels of uninjured controls. These results suggest that our therapeutic approach may have beneficial effects on both diaphragmatic recovery and sensory function.

Multimodal therapy strategies based on hydrogels for the repair of spinal cord injury

“…Olfactory ensheathing cells (OECs) are an important and clinically relevant cell transplantation population for SCI, and they can produce a suitable environment for axonal growth in the damaged CNS [ 77 ]. Studies have indicated that both collagen and fibrin hydrogels could improve the delivery [ 78 , 79 ], survival and retention of transplanted OECs for SCI.…”

Sustained Release of Human Adipose Tissue Stem Cell Secretome from Star‐Shaped Poly(ethylene glycol) Glycosaminoglycan Hydrogels Promotes Motor Improvements after Complete Transection in Spinal Cord Injury Rat Model

“…[9] Likewise, this approach was capable of increasing diaphragmatic activity and partially restoring sensory function in cervical level 2 (C2) hemisection SCI in rats. [17] The impact of cell transplantation on regenerative processes is mainly conveyed through their secreted bioactive molecules (secretome), including soluble proteins (cytokines, growth factors, and chemokines) and a vesicular fraction (exosomes), both of which have neuroprotective, neuroregenerative, and immunomodulatory capabilities. [13,18] Thus, ASCs-derived secretome has been shown to protect pheochromocytoma (PC12) cells from glutamate excitotoxicity and apoptosis by reducing the levels of cleaved-caspase-3.…”

Spermidine Crosslinked Gellan Gum-Based “Hydrogel Nanofibers” as Potential Tool for the Treatment of Nervous Tissue Injuries: A Formulation Study

“…20 Based on the experience gained with the electrospinning of GG-based solutions, the present work deals with the development of a fibrous scaffold to be implanted at the site of nervous tissue injuries. It consists of electrospun nanofibers based on GG, an attractive anionic polysaccharide in neural applications, [21][22][23][24][25][26][27] and spermidine (SP), a biologic polyamine. SP was used as multifunctional agent for the preparation of nanofibers.…”