Stem Cell-Based Cell Therapy for Spinal Cord Injury

Abstract

Traumatic injuries to the spinal cord lead to severe and permanent neurological deficits. Although no effective therapeutic option is currently available, recent animal studies have shown that cellular transplantation strategies hold promise to enhance functional recovery after spinal cord injury (SCI). This review is to analyze the experiments where transplantation of stem/progenitor cells produced successful functional outcome in animal models of SCI. There is no consensus yet on what kind of stem/progenitor cells is an ideal source for cellular grafts. Three kinds of stem/progenitor cells have been utilized in cell therapy in animal models of SCI: embryonic stem cells, bone marrow mesenchymal stem cells, and neural stem cells. Neural stem cells or fate-restricted neuronal or glial progenitor cells were preferably used because they have clear capacity to become neurons or glial cells after transplantation into the injured spinal cord. At least a part of functional deficits after SCI is attributable to chronic progressive demyelination. Therefore, several studies transplanted glial-restricted progenitors or oligodendrocyte precursors to target the demyelination process. Directed differentiation of stem/progenitor cells to oligodendrocyte lineage prior to transplantation or modulation of microenvironment in the injured spinal cord to promote oligodendroglial differentiation seems to be an effective strategy to increase the extent of remyelination. Transplanted stem/progenitor cells can also contribute to promoting axonal regeneration by functioning as cellular scaffolds for growing axons. Combinatorial approaches using polymer scaffolds to fill the lesion cavity or introducing regeneration-promoting genes will greatly increase the efficacy of cellular transplantation strategies for SCI.

Intrathecal transplantation of human neural stem cells overexpressing VEGF provide behavioral improvement, disease onset delay and survival extension in transgenic ALS mice

“…45 F3.VEGF cells were derived from F3 human NSC line and known to give rise to both neurons and glial cells. 28,46 F3 human NSC line has been shown to improve clinical outcome following brain transplantation in animal models of stroke, 45,46 spinal cord injury, 47 Parkinson disease, 48 Huntington disease 49 and lysosomal storage disease. 50 We identified that 12% of intrathecally introduced F3.VEGF cells migrated into the spinal cord and 52% cells were found along the meninges of the lumbar spinal cord 4 weeks after the injection.…”

Assessment of a Nuclear Affinity Labeling Method for Tracking Implanted Mesenchymal Stem Cells

“…Technically, these discrepancies may be caused in part by the use of peutic implantation of mesenchymal stem cells (MSCs), in particular, has been attempted in several clinical trials different cell labeling/tracking methods, cell administration protocols, timing of cell transplantation after tissue for hematological disorders, cardiovascular diseases, osteogenesis imperfecta, neurological pathologies, and even injury, and possibly misinterpretation of microscopy results (4). cancer therapy (9, 14,23). The ease of isolation, capacity for large-scale expansion, and alleged immunoprivileged Many cell labeling techniques have been used for tracking implanted stem cells in vivo.…”

Acquisition and Expansion of Adult Rat Bone Marrow Multipotent Mesenchymal Stromal Cells

“…The MFIs for CD90 cells were 9 552, 9 356 and 9 250; for nestin 3 620, son's and Alzheimer's disease, and amyothrophic lateral sclerosis), muscular dystrophy, myocardiopathies, and myocardial infarctions, belong to serious pathological conditions connected with high morbidity and mortality [6,10,13,21,22]. The treatment modalities of these diseases [3].…”

“…and with positive results, tested a modified method of harvesting and expansion of adult rat bone marrow MSCs enabling an easy autotransplantation to donors, thus avoiding possible adverse immune reaction [2,3,4,10,19,20].…”