A Phase III Clinical Trial Showing Limited Efficacy of Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury

Oh, Sun Kyu; Choi, Kyoung Hyo; Yoo, Jong Yoon; Kim, Dae Yul; Kim, Sang Joon; Jeon, Sang Ryong

doi:10.1227/neu.0000000000001056

Cited by 146 publications

(98 citation statements)

References 58 publications

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“…However, performance of all lesioned animals plateaued 2 months after injury ( Figure 6E) and would not have been expected to improve spontaneously after month 12 (40). Moreover, human clinical trials would be designed to detect late, within-subjects improvement from a chronic, stable baseline score, as in this study, because patients typically show little or no improvement in function at chronic post-injury time points (41)(42)(43).…”

Section: Resultsmentioning

confidence: 98%

Prolonged human neural stem cell maturation supports recovery in injured rodent CNS

Ceto²,

Wang³

et al. 2017

Journal of Clinical Investigation

100

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Section: Resultsmentioning

confidence: 98%

Prolonged human neural stem cell maturation supports recovery in injured rodent CNS

Ceto²,

Wang³

et al. 2017

Journal of Clinical Investigation

100

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“…Although treatment with MSCs has been previously shown to exert positive effects in rodent models of SCI (Alexanian et al., 2011, Nakajima et al., 2012), their prolonged therapeutic effects and success in human clinical trials have been limited (Oh et al., 2016, Park et al., 2012). Genetic modification of MSCs, for example by overexpression of neurotrophic or growth factors, can further enhance their well-known beneficial effects and improve therapeutic outcome following CNS trauma (reviewed in Cui et al., 2013).…”

Section: Discussionmentioning

confidence: 99%

Cell-Based Delivery of Interleukin-13 Directs Alternative Activation of Macrophages Resulting in Improved Functional Outcome after Spinal Cord Injury

et al. 2016

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SummaryThe therapeutic effects of mesenchymal stem cell (MSC) transplantation following spinal cord injury (SCI) to date have been limited. Therefore, we aimed to enhance the immunomodulatory properties of MSCs via continuous secretion of the anti-inflammatory cytokine interleukin-13 (IL-13). By using MSCs as carriers of IL-13 (MSC/IL-13), we investigated their therapeutic potential, compared with non-engineered MSCs, in a mouse model of SCI. We show that transplanted MSC/IL-13 significantly improve functional recovery following SCI, and also decrease lesion size and demyelinated area by more than 40%. Further histological analyses in CX3CR1EGFP/+ CCR2RFP/+ transgenic mice indicated that MSC/IL-13 significantly decrease the number of resident microglia and increase the number of alternatively activated macrophages. In addition, the number of macrophage-axon contacts in MSC/IL-13-treated mice was decreased by 50%, suggesting a reduction in axonal dieback. Our data provide evidence that transplantation of MSC/IL-13 leads to improved functional and histopathological recovery in a mouse model of SCI.

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“…Unfortunately, no clinical improvement of the neurological function had occurred at the end of this study [85]. Similarly, there are also data indicating that there is no significant improvement in Basso, Beattie, and Bresnahan (BBB) score after MSC transplantation for SCI [86, 87]. Pal et al reported that there is no effectiveness of the treatment involved after MSC injection for a of total 20 SCI patients during 1–3 years follow-up [88].…”

Section: Function Of Msc Transplantation After Scimentioning

confidence: 99%

Roles of Mesenchymal Stem Cells in Spinal Cord Injury

Zhang

2017

Stem Cells International

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Spinal cord injury (SCI) represents one of the most complicated and heterogeneous pathological processes of central nervous system (CNS) impairments, which is still beyond functional regeneration. Transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of the injured spinal cord tissues in animal models, and therefore, there is much interest in the clinical use of these cells. However, many questions which are essential to improve the therapy effects remain unanswered. For instance, the functional roles and related molecular regulatory mechanisms of MSCs in vivo are not yet completely determined. It is important for transplanted cells to migrate into the injured tissue, to survive and undergo neural differentiation, or to play neural protection roles by various mechanisms after SCI. In this review, we will focus on some of the recent knowledge about the biological behavior and function of MSCs in SCI. Meanwhile, we highlight the function of biomaterials to direct the behavior of MSCs based on our series of work on silk fibroin biomaterials and attempt to emphasize combinational strategies such as tissue engineering for functional improvement of SCI.

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A Phase III Clinical Trial Showing Limited Efficacy of Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury

Abstract: Single MSCs application to intramedullary and intradural space is safe, but has a very weak therapeutic effect compared with multiple MSCs injection. Further clinical trials to enhance the effect of MSCs injection are necessary.

Cited by 146 publications

References 58 publications

Prolonged human neural stem cell maturation supports recovery in injured rodent CNS

Prolonged human neural stem cell maturation supports recovery in injured rodent CNS

Cell-Based Delivery of Interleukin-13 Directs Alternative Activation of Macrophages Resulting in Improved Functional Outcome after Spinal Cord Injury

Roles of Mesenchymal Stem Cells in Spinal Cord Injury

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