Regenerative medicine for the treatment of spinal cord injury: more than just promises?

Abstract

Spinal cord injury triggers a complex set of events that lead to tissue healing without the restoration of normal function due to the poor regenerative capacity of the spinal cord. Nevertheless, current knowledge about the intrinsic regenerative ability of central nervous system axons, when in a supportive environment, has made the prospect of treating spinal cord injury a reality. Among the range of strategies under investigation, cell-based therapies offer the most promising results, due to the multifactorial roles that these cells can fulfil. However, the best cell source is still a matter of debate, as are clinical issues that include the optimal cell dose as well as the timing and route of administration. In this context, the role of biomaterials is gaining importance. These can not only act as vehicles for the administered cells but also, in the case of chronic lesions, can be used to fill the permanent cyst, thus creating a more favourable and conducive environment for axonal regeneration in addition to serving as local delivery systems of therapeutic agents to improve the regenerative milieu. Some of the candidate molecules for the future are discussed in view of the knowledge derived from studying the mechanisms that facilitate the intrinsic regenerative capacity of central nervous system neurons. The future challenge for the multidisciplinary teams working in the field is to translate the knowledge acquired in basic research into effective combinatorial therapies to be applied in the clinic.

An in vitro spinal cord injury model to screen neuroregenerative materials

“…Such synergistic approaches have the potential to regenerate the injured spinal cord with varying degrees of efficacy, but none have been successfully translated into the clinic [41]. The full potential of combinatorial strategies utilising aligned nanofibers with combinations of cells and biomolecules has yet to be elucidated, due in part to a heavy reliance on in vivo SCI models, in the absence of highthroughput, biologically-relevant in vitro screening models of SCI [5,42].…”

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

“…1 Current therapeutic approaches are being combined to activate the intrinsic neuronal regeneration capacity, such as blocking axon growth-inhibitory factors, reducing excitotoxicity and the inflammatory response, administration of neurotrophic factors, or using various types of stem and progenitor cells. 2,3 In addition to these approaches, tissue-engineered scaffolds play an important role in providing supportive substrates that contribute to replacing lost tissue and re-establishing damaged connections after SCI. [4][5][6][7] In terms of SCI repair, biomaterials, with their own intrinsic biological activity that would encourage endogenous tissue repair without the need for additional bioactive molecules such as exogenous growth factors or peptides, may provide high treatment effectivity together with relative ease of application and scalable manufacturing potential.…”

Role of Anesthetists in Human Embryonic Stem Cells Transplantation in Patients with Spinal Cord Injury

“…It is generally a sports, motor vehicle crashes/accidents or fall related injury. It leads to paralysis, loss of sensory and motor functions, accompanied with other multiple health problems such as urinary, cardiac and respiratory dysfunction which deteriorate the quality of life of the patient [3,4]. A series of cellular and biochemical events occurring during the injury are followed by a cascade of reactive changes such as inflammation, hemorrhagic necrosis, edema and demyelination.…”

“…They, together, result in loss of neurons and myelinating oligodendrocytes, vascular destruction, scarring and axonopathy accompanied with de-nervation below the central lesion site and cell death [5,6]. The loss of oligodendrocytes and demyelination also leads to the progressive and delayed degeneration of residual axonal tracts [3].…”

“…routes of catheterization/administration have been previously reported [3,11]. Further developments of catheterization systems for various clinical studies involve various other routes for administering hESCs such as intramuscular, intravenous, intrathecal, epidural, caudal, brachial plexus, popliteal and/or deep spinal muscle injection, etc.…”