Transplantation of bone marrow stem cells into spinal cord lesions enhances axonal regeneration and promotes functional recovery in animal studies. There are two types of adult bone marrow stem cell; hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). The mechanisms by which HSCs and MSCs might promote spinal cord repair following transplantation have been extensively investigated. The objective of this review is to discuss these mechanisms; we briefly consider the controversial topic of HSC and MSC transdifferentiation into central nervous system cells but focus on the neurotrophic, tissue sparing, and reparative action of MSC grafts in the context of the spinal cord injury (SCI) milieu. We then discuss some of the specific issues related to the translation of HSC and MSC therapies for patients with SCI and present a comprehensive critique of the current bone marrow cell clinical trials for the treatment of SCI to date. Stem Cells 2011;29:169–178

Study design:This is a mixed-method consensus development project.Objectives:The objective of this study was to identify a top ten list of priorities for future research into spinal cord injury (SCI).Setting:The British Spinal Cord Injury Priority Setting Partnership was established in 2013 and completed in 2014. Stakeholders included consumer organisations, healthcare professional societies and caregivers.Methods:This partnership involved the following four key stages: (i) gathering of research questions, (ii) checking of existing research evidence, (iii) interim prioritisation and (iv) a final consensus meeting to reach agreement on the top ten research priorities. Adult individuals with spinal cord dysfunction because of trauma or non-traumatic causes, including transverse myelitis, and individuals with a cauda equina syndrome (henceforth grouped and referred to as SCI) were invited to participate in this priority setting partnership.Results:We collected 784 questions from 403 survey respondents (290 individuals with SCI), which, after merging duplicate questions and checking systematic reviews for evidence, were reduced to 109 unique unanswered research questions. A total of 293 people (211 individuals with SCI) participated in the interim prioritisation process, leading to the identification of 25 priorities. At a final consensus meeting, a representative group of individuals with SCI, caregivers and health professionals agreed on their top ten research priorities.Conclusion:Following a comprehensive, rigorous and inclusive process, with participation from individuals with SCI, caregivers and health professionals, the SCI research agenda has been defined by people to whom it matters most and should inform the scope and future activities of funders and researchers for the years to come.Sponsorship:The NIHR Oxford Biomedical Research Centre provided core funding for this project.

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Study design: Previous studies have shown that transplantation of bone marrow stromal cells (MSCs) in animal models of spinal cord injury (SCI) encourages functional recovery. Here, we have examined the growth in cell culture of MSCs isolated from individuals with SCI, compared with non-SCI donors. Setting: Centre for Spinal Studies, Midland Centre for Spinal Injuries, RJAH Orthopaedic Hospital, Oswestry, UK. Methods: Bone marrow was harvested from the iliac crest of donors with long-term SCI (43 months, n ¼ 9) or from non-SCI donors (n ¼ 7). Mononuclear cells were plated out into tissue culture flasks and the adherent MSC population subsequently expanded in monolayer culture. MSC were passaged by trypsinization at 70% confluence and routinely seeded into new flasks at a density of 5 Â 10 3 cells per cm 2 . Expanded cell cultures were phenotypically characterized by CD-immunoprofiling and by their differentiation potential along chondrocyte, osteoblast and adipocyte lineages. The influence of cellseeding density on the rate of cell culture expansion and degree of cell senescence was examined in separate experiments. Results: In SCI, but not in non-SCI donors the number of adherent cells harvested at passage I was age-related. The proliferation rate (culture doubling times) between passages I and II was significantly greater in cultures from SCI donors with cervical lesions than in those with thoracic lesions. There was no significant difference, however, in either the overall cell harvests at passages I or II or in the culture doubling times between SCI and non-SCI donors. At passage II, more than 95% of cells were CD34Àve, CD45Àve and CD105 þ ve, which is characteristic of human MSC cultures. Furthermore, passage II cells differentiated along all three mesenchymal lineages tested. Seeding passage I-III cells at cell densities lower than 5 Â 10 3 cells per cm 2 significantly reduced culture doubling times and significantly increased overall cell harvests while having no effect on cell senescence. Conclusion: MSCs from individuals with SCI can be successfully isolated and expanded in culture; this is encouraging for the future development of MSC transplantation therapies to treat SCI. Age, level of spinal injury and cell-seeding density were all found to relate to the growth kinetics of MSC cultures in vitro, albeit in a small sample group. Therefore, these factors should be considered if either the overall number or the timing of MSC transplantations post-injury is found to relate to functional recovery.

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