Bone marrow stromal cells can achieve cure of chronic paraplegic rats: Functional and morphological outcome one year after transplantation

Zurita, Mercedes; Vaquero, Jesús

doi:10.1016/j.neulet.2006.03.069

Cited by 118 publications

(65 citation statements)

References 14 publications

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“…[2][3][4][5][6][7] However, there is also evidence to suggest that SCI in humans may influence the activity of other bone marrow cells. SCI is known to depress natural and adaptive immunity and in vitro studies have demonstrated not only decreased lymphocyte function 15,16 but also reduced long-term colony formation of haemopoietic stem cells.…”

Section: Discussionmentioning

confidence: 99%

“…MSC transplantation has been demonstrated to be beneficial in acute/subacute and chronic models of SCI, and therefore these are all clinical targets. [2][3][4][5][6][7] However, following local ethical guidelines, bone marrow aspirates were harvested only from individuals with a complete long-term Frankel grade A SCI, a minimum of 3 months post-injury.…”

Section: Discussionmentioning

confidence: 99%

“…1 Somewhat surprisingly, MSCs have received considerable interest as possible donor cells in the development of cell transplantation therapies for spinal cord injury (SCI). [2][3][4][5][6][7] There are, however, a number of reasons for this. First and foremost, MSC transplantation has been demonstrated to enhance axonal regeneration and promote functional recovery in a variety of animal models of SCI.…”

Section: Introductionmentioning

confidence: 99%

“…First and foremost, MSC transplantation has been demonstrated to enhance axonal regeneration and promote functional recovery in a variety of animal models of SCI. [2][3][4][5][6][7] These studies have shown that transplanted MSCs integrate into host tissue following transplantation, supporting and remyelinating axons that traverse the injury site. MSCs also synthesize a number of growth factors that may contribute to tissue sparing and axonal regeneration, including nerve growth factor and brain-derived neurotrophic factor.…”

Section: Introductionmentioning

confidence: 99%

“…8 Importantly, though, MSCs represent an attractive donor source for various cell transplantation programmes, as they can be repeatedly isolated from bone marrow with relative ease, normally expanded into large numbers in vitro and reintroduced into patients as autografts, which prevents the need for immune rejection drugs in the clinical setting. 9 If donor cell number is a critical factor to the success of cell grafting for SCI treatment, as is likely to be the case, then it is important to note that the typical injury in rodent models of SCI is only a few millimetres in length, [2][3][4][5][6][7] whereas the length of lesions in humans can reach several centimetres. Recently, using an in vitro model, we have shown that human MSCs promote nerve growth over inhibitory molecules present at the lesion site in SCI; furthermore, the number of nerves that were subsequently able to grow over these molecules was related to the number of MSCs present.…”

Section: Introductionmentioning

confidence: 99%

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The cell culture expansion of bone marrow stromal cells from humans with spinal cord injury: implications for future cell transplantation therapy

et al. 2008

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The cell culture expansion of bone marrow stromal cells from humans with spinal cord injury: implications for future cell transplantation therapy

et al. 2008

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The evolving concept of mesenchymal stromal cells in regenerative medicine

Teixeira

Pires

Serra

et al. 2016

The Biology and Therapeutic Application of Mesenchymal Cells

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Stem Cells: Current Approach and Future Prospects in Spinal Cord Injury Repair

Zhang

Huang²,

Qian

et al. 2010

The Anatomical Record

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Spinal cord injury (SCI) invariably results in the loss of neurons and axonal degeneration at the lesion site, leading to permanent paralysis and loss of sensation. There has been no successful treatment for severe spinal cord injuries to recover back to normal function yet. Studies have shown that the transplantation of stem cells may provide an effective treatment for SCI because of the self-renewing and multipotential nature of these cells. Stem cells have the capability to repair injured nervous tissue through replacement of damaged cells, neuroprotection, or the creation of an environment conducive to regeneration by endogenous cells. Up to today several types of stem cells have been transplanted into the injured spinal cord. However, the question of which cell type is most beneficial for SCI treatment is still unresolved. There are still several limitations to the current data sets which require further investigation. Anat Rec, 293:519-530, 2010. V V C 2009 Wiley-Liss, Inc.

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Bone marrow stromal cells can achieve cure of chronic paraplegic rats: Functional and morphological outcome one year after transplantation

Cited by 118 publications

References 14 publications

The cell culture expansion of bone marrow stromal cells from humans with spinal cord injury: implications for future cell transplantation therapy

The cell culture expansion of bone marrow stromal cells from humans with spinal cord injury: implications for future cell transplantation therapy

The evolving concept of mesenchymal stromal cells in regenerative medicine

Stem Cells: Current Approach and Future Prospects in Spinal Cord Injury Repair

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