Induced Pluripotent Stem Cells for Traumatic Spinal Cord Injury

Khazaei, Mohamad; Ahuja, Christopher S.; Fehlings, Michael G.

doi:10.3389/fcell.2016.00152

Cited by 57 publications

(54 citation statements)

References 90 publications

(98 reference statements)

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“…The various cell types that have been assessed in preclinical studies include neural stem or precursor cells, oligodendrocyte precursor cells, olfactory ensheathing cells, Schwann cells, umbilical cord mesenchymal stem cells, amongst others 176,193 . Cell transplantation into the transected cord has been shown to promote the recovery of motor function, including coordinated walking 194 , paw use and climbing 195 , in addition to improved bladder function 196 and phrenic nerve activity 197 in animal models.…”

Section: [H2] Current Clinical Studiesmentioning

confidence: 99%

Traumatic spinal cord injury

Ahuja

Wilson

Nori

et al. 2017

Nat Rev Dis Primers

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1,353

1,166

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Traumatic spinal cord injury (SCI) has devastating consequences for the physical, social and vocational well-being of patients. The demographic of SCIs is shifting such that an increasing proportion of older individuals are being affected. Pathophysiologically, the initial mechanical trauma (the primary injury) permeabilizes neurons and glia and initiates a secondary injury cascade that leads to progressive cell death and spinal cord damage over the subsequent weeks. Over time, the lesion remodels and is composed of cystic cavitations and a glial scar, both of which potently inhibit regeneration. Several animal models and complementary behavioural tests of SCI have been developed to mimic this pathological process and form the basis for the development of preclinical and translational neuroprotective and neuroregenerative strategies. Diagnosis requires a thorough patient history, standardized neurological physical examination and radiographic imaging of the spinal cord. Following diagnosis, several interventions need to be rapidly applied, including haemodynamic monitoring in the intensive care unit, early surgical decompression, blood pressure augmentation and, potentially, the administration of methylprednisolone. Managing the complications of SCI, such as bowel and bladder dysfunction, the formation of pressure sores and infections, is key to address all facets of the patient's injury experience.

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Section: [H2] Current Clinical Studiesmentioning

confidence: 99%

Traumatic spinal cord injury

Ahuja

Wilson

Nori

et al. 2017

Nat Rev Dis Primers

Self Cite

1,353

1,166

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“…However, using hiPSCs avoids the controversial ethical issues associated with human embryo derived hESCs. Furthermore, hiPSCs can be more readily used for clinical treatment, as patient‐derived hiPSCs reduce the risk of immune rejection when transplanted back into the original patient …”

Section: Introductionmentioning

confidence: 99%

Engineering Neural Tissue from Human Pluripotent Stem Cells Using Novel Small Molecule Releasing Microspheres

2018

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Here a novel technique for engineering neural tissue consisting of motor neurons by combining human‐induced pluripotent stem cells (hiPSCs) with small molecules releasing microspheres is demonstrated. First, the small molecule purmorphamine (puro) is successfully encapsulated into poly ε‐caprolactone (PCL) microspheres using a single emulsion oil‐in‐water (o/w) method for the first time with an efficiency of (84% ± 2.12%). These microspheres release 91% ± 1.7% of the encapsulated puro in a controlled fashion over 46 days. Puro microspheres, along with previously characterized retinoic acid (RA) releasing microspheres, are then incorporated into hiPSC aggregates to engineer neural tissue. The combination of puro and RA microspheres promotes hiPSC differentiation as indicated by the expression of multiple neural markers, including the neuronal marker β‐tubulin III (βT‐III), and the transcription factor Olig2 (7.69 ± 8.38%) on day 28. These tissues express the motor neuron marker HB9 (24.85 ± 4.51%) on day 35, and the mature motor neuron marker ChaT (12.35 ± 4.17%) on day 60. These engineered tissues can be used for regenerative medicine applications such as treating spinal cord injury (SCI), disease modeling, and drug screening.

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“…ncRNAs can reduce the amount of reprogramming factors as they specifically target multiple pathways. Traditionally, lentivirus has been the reprogramming vector of choice; other viral vectors such as Sendai and adenovirus to lower transformation risks have been used with lower efficacy [122][123][124]. Excellent reviews describing more details for reprogramming protocol improvements are available [125][126][127].…”

Section: Induced Pluripotent Stem Cells (Ipscs)mentioning

confidence: 99%

Culturing Adult Stem Cells for Cell-Based Therapeutics: Neuroimmune Applications

Moreno‐Manzano¹,

Oltra²

2019

Cell Culture

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Pluripotent stem cells can be successfully isolated from a variety of tissues from adult organisms. This fact opens the exciting possibility of cell-based therapies for a large number of clinical treatments. However, the development of optimized protocols to obtain, grow, and cryopreserve cells, as well as that of effective clinical treatment procedures, is no easy task. The therapeutic potential of cells expanded in vitro depends on a multitude of factors including isolation procedures, donor and tissue types, expansion and preservation methods, etc. Researchers are investing great efforts to determine which of these many variables significantly impact downstream performance of in vitro expanded stem cells by studying associated changes in molecular profiles and their effect on the host immune system. This chapter reviews the current status of stem cell production and its derivatives, which are paving the way to different treatments in the clinic. Due to the research interests of our labs, particular emphasis is placed on the potential benefits of stem cell-based therapeutics for the treatment of spinal cord injuries and the neuroimmune disease myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) not only derived from differentiation and cell engraftment mechanisms but also due to the antiinflammatory and immunoregulatory capacities of these cells.

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Induced Pluripotent Stem Cells for Traumatic Spinal Cord Injury

Cited by 57 publications

References 90 publications

Traumatic spinal cord injury

Traumatic spinal cord injury

Engineering Neural Tissue from Human Pluripotent Stem Cells Using Novel Small Molecule Releasing Microspheres

Culturing Adult Stem Cells for Cell-Based Therapeutics: Neuroimmune Applications

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