4.6 Article

Promoting motor functions in a spinal cord injury model of rats using transplantation of differentiated human olfactory stem cells: A step towards future therapy

Journal

BEHAVIOURAL BRAIN RESEARCH
Volume 405, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.bbr.2021.113205

Keywords

Human olfactory ecto-mesenchymal stem cells; (hOE-MSCs); motor neuron; Engraftment; Spinal cord injury; Stem cells

Funding

  1. ENT and Head & Neck Research Center
  2. Department in Iran University of Medical Sciences [9822215316]

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The study demonstrated that motor neuron-like cells derived from human olfactory ecto-mesenchymal stem cells (hOE-MSCs) have potential therapeutic effects for spinal cord injuries. Through cell transplantation and induction, significant improvements were observed in locomotor and sensory scores of rats with spinal cord injuries, indicating the potential of hOE-MSCs for SCI treatment.
Human olfactory ecto-mesenchymal stem cells (hOE-MSCs) derived from the human olfactory mucosa (OM) can be easily isolated and expanded in cultures while their immense plasticity is maintained. To mitigate ethical concerns, the hOE-MSCs can be also transplanted across allogeneic barriers, making them desirable cells for clinical applications. The main purpose of this study was to evaluate the effects of administering the hOE-MSCs on a spinal cord injury (SCI) model of rats. These cells were accordingly isolated and cultured, and then treated in the neurobasal medium containing serum-free Dulbecco?s Modified Essential Medium (DMEM) and Ham?s F-12 Medium (DMEM/F12) with 2% B27 for two days. Afterwards, the pre-induced cells were incubated in N2B27 with basic fibroblast growth factor (bFGF), fibroblast growth factor 8b (FGF8b), sonic hedgehog (SHH), and ascorbic acid (vitamin C) for six days. The efficacy of the induced cells was additionally evaluated using immunocytochemistry (ICC) and real-time polymerase chain reaction (RT-PCR). The differentiated cells were similarly transplanted into the SC contusions. Functional recovery was further conducted on a weekly basis for eight consecutive weeks. Moreover, cell integration was assessed via conventional histology and ICC, whose results revealed the expression of choline acetyltransferase (ChAT) marker at the induction stage. According to the RT-PCR findings, the highest expression level of insulin gene-enhancer protein (islet-1), oligodendrocyte transcription factor (Olig2), and homeobox protein HB9 was observed at the induction stage. The number of engraftment cells also rose (approximately by 2.5 % ? 0.1) in the motor neuron-like cells derived from the hOEMSCs-grafted group compared with the OE-MSCs-grafted one. The functional analysis correspondingly revealed that locomotor and sensory scores considerably improved in the rats in the treatment group. These findings suggested that motor neuron-like cells derived from the hOE-MSCs could be utilized as an alternative cell-based therapeutic strategy for SCI.

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