Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

Laroni, Alice; Rosbo, Nicole Kerlero de; Uccelli, Antonio

doi:10.1016/j.imlet.2015.08.007

Cited by 60 publications

(39 citation statements)

References 124 publications

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“…Mesenchymal stem cells (MSCs) have to date been one of the most promising progenitor cell types, associated with diverse functional capabilities and extensive tissue regenerative potential. MSCs can migrate to areas of injury [1] and integrate with damaged tissues, where they mediate immunomodulatory [2][3][4], antiapoptotic, and anti-inflammatory effects through the secretion of various neurotrophic factors and cytokines and signaling pathway activation through specific receptors on target cells [5]. These specific features, along with multiple studies reporting the ability of MSCs to promote regeneration of nervous tissues in the brain and spinal cord, support the potential of MSCs as treatments of neurodegenerative conditions and traumatic brain and spinal cord injury (SCI) [6,7].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

et al. 2019

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Here, we provide a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix, in small (rat) and large (pig) spinal cord injury (SCI) models during subacute period of spinal contusion. Results of behavioral, electrophysiological, and histological assessment as well as immunohistochemistry and real-time polymerase chain reaction analysis suggest that application of AD-MSCs combined with a fibrin matrix within the subacute period in rats (2 weeks after injury), provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in: (1) restoration of locomotor activity and conduction along spinal axons; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of microglial and astroglial activation. The effect of an autologous application of AD-MSCs during the subacute period after spinal contusion was also confirmed in pigs (6 weeks after injury). Effects included: (1) partial restoration of the somatosensory spinal pathways; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of astroglial activation in dorsal root entry zone. However, pigs only partially replicated the findings observed in rats. Together, these results indicate application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

et al. 2019

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“…Furthermore, a phase 2a proof-of-concept study showed an improvement of visual acuity and shortening of delayed visual-evoked response latency after intravenous infusion of autologous bone marrow MSCs in SPMS patients (ClinicalTrials.gov: NCT00395200) [71]. Both clinical trials are based on preclinical data showing immunomodulatory as well as neuroprotective effects in EAE [72,73] and are particularly important for safety reasons as available data also demonstrated possible disease worsening in CD8 þ T-cell-driven myelin oligodendrocyte glycoprotein-EAE (MOG-EAE) [74]. However, it cannot be ignored that MSCs mainly exert positive immunomodulatory effects such as an impairment of T-cell trafficking across the BBB [75] and induction of neuroprotective microglia phenotypes [76].…”

Section: Exogenous Cell-based Approachesmentioning

confidence: 99%

Recent achievements in stem cell-mediated myelin repair

Jadasz

Lubetzki

Zalc

et al. 2016

Current Opinion in Neurology

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“…Mesenchymal stem cells (MSCs) have to date been one of the most promising progenitor cell types, associated with diverse functional capabilities and extensive tissue regenerative potential. MSCs can migrate to area of injury (Nitzsche et al, 2017) and integrate with damaged tissues, they also have immunomodulatory (Hashemi et al, 2013;Laroni et al, 2015;, anti-apoptotic, and anti-inflammatory effects due to secretion of various neurotrophic factors and cytokines (a paracrine mechanism of MSCs action), which activating signaling pathways through specific receptors on target cells (Samsonraj et al, 2017). These specific features of MSCs support their potential for treatment of neurodegenerative conditions and traumatic brain and spinal cord injury.…”

Section: Introductionmentioning

confidence: 97%

Mesenchymal stem cells therapy for spinal cord contusion: a comparative study on small and large animal models

Mukhamedshina

Shulman

Ogurcov

et al. 2019

Preprint

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Here, we provided a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix in a small (rat) and large (pig) spinal cord injury (SCI) model during sub-acute period of spinal contusion. Results of behavioral, electrophysiological, histological assessment, as well as results of immunohistochemistry and RT-PCR analysis suggest that application of AD-MSCs combined with a fibrin matrix in a subacute period in rats (2 weeks after injury) provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in (1) restoration of locomotor activity and conduction along spinal axons, (2) reduction of post-traumatic cavitation and enhancing tissue retention, and (3) modulation of microglial and astroglial activation. The effect of therapy with an autologous application of AD-MSCs was also confirmed in subacute period after spinal contusion in pigs (6 weeks after injury), however, with only partial replication of the findings observed in rats, i.e. (1) partial restoration of the somatosensory spinal pathways, (2) reduction of post-traumatic cavitation and enhancing tissue retention, and (3) modulation of astroglial activation in dorsal root entry zone. The results of this study suggest that application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.

show abstract

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

Cited by 60 publications

References 124 publications

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

Recent achievements in stem cell-mediated myelin repair

Mesenchymal stem cells therapy for spinal cord contusion: a comparative study on small and large animal models

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