Long-term survival and development of fetal ventral spinal grafts into the motoneuron-depleted rat spinal cord: Role of donor age

Gulino, Rosario; Litrico, Laura; Leanza, Giampiero

doi:10.1016/j.brainres.2010.02.003

Cited by 13 publications

(7 citation statements)

References 31 publications

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“…Moreover, it has been shown that cell proliferation and differentiation, as well as bone matrix formation are improved within biomaterials containing hydroxyapatite when compared to scaffolds without hydroxyapatite 36 . As occurring in many transplantation models, the local tissue microenvironment is an important factor affecting cell behavior, along with the biomaterial composition and intrinsic properties of cells 6 , 24 , 25 , 32 , 37 . Therefore, further studies should address this question by implanting the scaffolds into other organs, including injured bone sites.…”

Section: Discussionmentioning

confidence: 99%

Human adipose-derived mesenchymal stem cells seeded into a collagen-hydroxyapatite scaffold promote bone augmentation after implantation in the mouse

Calabrese

Giuffrida²,

Forte³

et al. 2017

Sci Rep

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Traumatic injury or surgical excision of diseased bone tissue usually require the reconstruction of large bone defects unable to heal spontaneously, especially in older individuals. This is a big challenge requiring the development of biomaterials mimicking the bone structure and capable of inducing the right commitment of cells seeded within the scaffold. In particular, given their properties and large availability, the human adipose-derived stem cells are considered as the better candidate for autologous cell transplantation. In order to evaluate the regenerative potential of these cells along with an osteoinductive biomaterial, we have used collagen/hydroxyapatite scaffolds to test ectopic bone formation after subcutaneous implantation in mice. The process was analysed both in vivo, by Fluorescent Molecular Tomography (FMT), and ex vivo, to evaluate the formation of bone and vascular structures. The results have shown that the biomaterial could itself be able of promoting differentiation of host cells and bone formation, probably by means of its intrinsic chemical and structural properties, namely the microenvironment. However, when charged with human mesenchymal stem cells, the ectopic bone formation within the scaffold was increased. We believe that these results represent an important advancement in the field of bone physiology, as well as in regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Human adipose-derived mesenchymal stem cells seeded into a collagen-hydroxyapatite scaffold promote bone augmentation after implantation in the mouse

Calabrese

Giuffrida²,

Forte³

et al. 2017

Sci Rep

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“…The efficiency of CTB-SAP in producing selective motoneuron depletion after injection in the target muscle has been proven [ 7 – 10 ], thus providing an effective model of primary neurodegeneration. Similar methods of selective neurotoxic lesion have been already used in our laboratory [ 58 , 59 ]. Finally, a group of animals were left untreated and used as normal controls for western blot experiments (NC; n = 7).…”

Section: Methodsmentioning

confidence: 99%

Novel Mechanisms of Spinal Cord Plasticity in a Mouse Model of Motoneuron Disease

Gulino

Parenti

Gulisano

2015

BioMed Research International

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A hopeful spinal cord repairing strategy involves the activation of neural precursor cells. Unfortunately, their ability to generate neurons after injury appears limited. Another process promoting functional recovery is synaptic plasticity. We have previously studied some mechanisms of spinal plasticity involving BDNF, Shh, Notch-1, Numb, and Noggin, by using a mouse model of motoneuron depletion induced by cholera toxin-B saporin. TDP-43 is a nuclear RNA/DNA binding protein involved in amyotrophic lateral sclerosis. Interestingly, TDP-43 could be localized at the synapse and affect synaptic strength. Here, we would like to deepen the investigation of this model of spinal plasticity. After lesion, we observed a glial reaction and an activity-dependent modification of Shh, Noggin, and Numb proteins. By using multivariate regression models, we found that Shh and Noggin could affect motor performance and that these proteins could be associated with both TDP-43 and Numb. Our data suggest that TDP-43 is likely an important regulator of synaptic plasticity, probably in collaboration with other proteins involved in both neurogenesis and synaptic plasticity. Moreover, given the rapidly increasing knowledge about spinal cord plasticity, we believe that further efforts to achieve spinal cord repair by stimulating the intrinsic potential of spinal cord will produce interesting results.

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“…We have previously generated a model of selective MN degeneration by injecting cholera toxin-B saporin (CTB-Sap) [11,12] into the gastrocnemius muscle (GM) of wild-type mice [13]. This represents a reductionist model of focal depletion of SC MNs [12,13,14], where the effects of selective MN removal could be studied in experimental conditions that are markedly different than those in genetic models of disease. Considering that synaptic failure is one of the most recent and trusted hypotheses of ALS pathogenesis [6], this model could represent a promising tool for studying plastic changes after MN degeneration in the absence of other confounding factors that are present in other more complex animal models, as well as in patients.…”

Section: Introductionmentioning

confidence: 99%

Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss

Gulino

Vicario

Giunta

et al. 2019

IJMS

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Despite the relevant research efforts, the causes of amyotrophic lateral sclerosis (ALS) are still unknown and no effective cure is available. Many authors suggest that ALS is a multi-system disease caused by a network failure instead of a cell-autonomous pathology restricted to motoneurons. Although motoneuronal loss is the critical hallmark of ALS given their specific vulnerability, other cell populations, including muscle and glial cells, are involved in disease onset and progression, but unraveling their specific role and crosstalk requires further investigation. In particular, little is known about the plastic changes of the degenerating motor system. These spontaneous compensatory processes are unable to halt the disease progression, but their elucidation and possible use as a therapeutic target represents an important aim of ALS research. Genetic animal models of disease represent useful tools to validate proven hypotheses or to test potential therapies, and the conception of novel hypotheses about ALS causes or the study of pathogenic mechanisms may be advantaged by the use of relatively simple in vivo models recapitulating specific aspects of the disease, thus avoiding the inclusion of too many confounding factors in an experimental setting. Here, we used a neurotoxic model of spinal motoneuron depletion induced by injection of cholera toxin-B saporin in the gastrocnemius muscle to investigate the possible occurrence of compensatory changes in both the muscle and spinal cord. The results showed that, following the lesion, the skeletal muscle became atrophic and displayed electromyographic activity similar to that observed in ALS patients. Moreover, the changes in muscle fiber morphology were different from that observed in ALS models, thus suggesting that some muscular effects of disease may be primary effects instead of being simply caused by denervation. Notably, we found plastic changes in the surviving motoneurons that can produce a functional restoration probably similar to the compensatory changes occurring in disease. These changes could be at least partially driven by glutamatergic signaling, and astrocytes contacting the surviving motoneurons may support this process.

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Long-term survival and development of fetal ventral spinal grafts into the motoneuron-depleted rat spinal cord: Role of donor age

Cited by 13 publications

References 31 publications

Human adipose-derived mesenchymal stem cells seeded into a collagen-hydroxyapatite scaffold promote bone augmentation after implantation in the mouse

Human adipose-derived mesenchymal stem cells seeded into a collagen-hydroxyapatite scaffold promote bone augmentation after implantation in the mouse

Novel Mechanisms of Spinal Cord Plasticity in a Mouse Model of Motoneuron Disease

Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss

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