Cell Therapy from Bench to Bedside Translation in CNS Neurorestoratology Era

Abstract

Recent advances in cell biology, neural injury and repair, and the progress towards development of neurorestorative interventions are the basis for increased optimism. Based on the complexity of the processes of demyelination and remyelination, degeneration and regeneration, damage and repair, functional loss and recovery, it would be expected that effective therapeutic approaches will require a combination of strategies encompassing neuroplasticity, immunomodulation, neuroprotection, neurorepair, neuroreplacement, and neuromodulation. Cell-based restorative treatment has become a new trend, and increasing data worldwide have strongly proven that it has a pivotal therapeutic value in CNS disease. Moreover, functional neurorestoration has been achieved to a certain extent in the CNS clinically. Up to now, the cells successfully used in preclinical experiments and/or clinical trial/treatment include fetal/embryonic brain and spinal cord tissue, stem cells (embryonic stem cells, neural stem/progenitor cells, hematopoietic stem cells, adipose-derived adult stem/precursor cells, skin-derived precursor, induced pluripotent stem cells), glial cells (Schwann cells, oligodendrocyte, olfactory ensheathing cells, astrocytes, microglia, tanycytes), neuronal cells (various phenotypic neurons and Purkinje cells), mesenchymal stromal cells originating from bone marrow, umbilical cord, and umbilical cord blood, epithelial cells derived from the layer of retina and amnion, menstrual bloodderived stem cells, Sertoli cells, and active macrophages, etc. Proof-of-concept indicates that we have now entered a new era in neurorestoratology.

Cell-based neurorestorative therapy for postpoliomyelitis syndrome: a case report

“…25,26 It was applied for olfactory ensheathing cells, neural progenitor cells, stromal cells, Schwann cells, and so on. 12 Also, pathways of cell therapy include intracerebral, intraspinal, intravenous, intramuscular, intrathecal injection, and so on. Basic and clinical researches performed by our team gave some good results.…”

“…With rapid development and clinical advancement in neurorestoration, neurorestoratology has become a distinct discipline within neurosciences. [8][9][10][11][12][13] Various neurorestorative strategies or therapies have been widely used in clinical practice. Evidence has shown the benefits of cell-based neurorestorative therapy for patients with spinal cord injury, amyotrophic lateral sclerosis, stroke, multiple sclerosis, cerebral palsy, and other refractory nerve diseases.…”

Olfactory ensheathing cell transplantation for a patient with chronic sciatic nerve injury

“…After being transplanted, they can restore, promote, and maintain the integrity of impaired or lost neuronal functions and/or structures through mechanisms of neuroprotection, supporting axonal regeneration, remyelination, neurorepair, neuroplasticity, neuromodulation, neurogenesis, angiogenesis, anti-inflammatory response, etc. 17,18 Following OEC transplantation, patients with complete chronic SCI, amyotrophic lateral sclerosis, chronic stroke, cerebral palsy, multiple system atrophy, Alzheimer's disease, etc could benefit from the restoration of some neurological functions and their quality of life could be improved. [19][20][21][22][23][24][25] During the period of recovery after acute phase, Schwann cells play an important role in peripheral nerve axonal regeneration and remyelination through providing neurotrophic support, guiding axonal regeneration, and myelinating the regenerated axons.…”

Developmental history of neurorestoratology

“…Over 30 types of cells and tissues have been successfully used in preclinical experiments. 34 A number of cell transplantation clinical studies worldwide were started during this period. The earliest clinical trial of cultured human neuronal cell transplantation into brain parenchyma for patients with stroke was done by Kondziolka et al 35 The earliest clinical trials or studies of OEC transplantation into spinal cord parenchyma were started for spinal cord injury (SCI) by Huang et al and Rabinovich et al 36,37 Olfactory mucosa tissue transplantation was done by Lima et al in 2001.…”