Systemic Dental Pulp Stem Cell Secretome Therapy in a Mouse Model of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron (MN) disease with no cure. Accumulating evidence indicates ALS involves a complex interaction between central glia and the peripheral immune response and neuromuscular interface. Stem cell secretomes contain various beneficial trophic factors and cytokines, and we recently demonstrated that administration of the secretome of adipose-derived stem cells (ASCs) during early neuromuscular junction (NMJ) denervation in the mutant superoxide dismutase (mSOD1G93A) ALS mouse ameliorated NMJ disruption. In the present study, we hypothesized that administration of dental pulp stem cell secretome in the form of conditioned medium (DPSC-CM) at different stages of disease would promote NMJ innervation, prevent MN loss and extend lifespan. Our findings show that DPSC-CM significantly improved NMJ innervation at postnatal day (PD) 47 compared to vehicle treated mSOD1G93A mice (p < 0.05). During late pre-symptomatic stages (PD70-P91), DPSC-CM significantly increased MN survival (p < 0.01) and NMJ preservation (p < 0.05), while reactive gliosis in the ventral horn remained unaffected. For DPSC-CM treated mSOD1G93A mice beginning at symptom onset, post-onset days of survival as well as overall lifespan was significantly increased compared to vehicle treated mice (p < 0.05). This is the first study to show therapeutic benefits of systemic DPSC secretome in experimental ALS, and establishes a foundation for future research into the treatment effects and mechanistic analyses of DPSC and other stem cell secretome therapies in ALS.

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Intraspinal Stem Cell Transplantation in Amyotrophic Lateral Sclerosis

Neurosurgery ◽

10.1227/neu.0000000000000156 ◽

2013 ◽

Vol 74 (1) ◽

pp. 77-87 ◽

Cited By ~ 62

Author(s):

Jonathan Riley ◽

Jonathan Glass ◽

Eva L. Feldman ◽

Meraida Polak ◽

Jane Bordeau ◽

...

Keyword(s):

Spinal Cord ◽

Amyotrophic Lateral Sclerosis ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Neural Stem Cell ◽

Ventral Horn ◽

Perioperative Morbidity ◽

Group D ◽

Lateral Sclerosis

Abstract BACKGROUND: The first US Food and Drug Administration approved clinical trial for a stem cell-based treatment of amyotrophic lateral sclerosis has now been completed. OBJECTIVE: Primary aims assessed the safety of a direct microinjection-based technique and the toxicity of neural stem cell transplantation to the ventral horn of the cervical and thoracolumbar spinal cord. Results from thoracolumbar-only microinjection groups have been previously published. Cervical and cervical plus thoracolumbar microinjection group perioperative morbidity results are presented. METHODS: Eighteen microinjection procedures (n = 12 thoracolumbar [T10/11], n = 6 cervical [C3-5]) delivered NSI-566RSC (Neuralstem, Inc), a human neural stem cell, to 15 patients in 5 cohorts. Each injection series comprised 5 injections of 10 μL at 4-mm intervals. The patients in group A (n = 6) were nonambulatory and received unilateral (n = 3) or bilateral (n = 3) thoracolumbar microinjections. The patients in groups B to E were ambulatory and received either unilateral (group B, n = 3) or bilateral (group C, n = 3) thoracolumbar microinjection. Group D and E patients received unilateral cervical (group D, n = 3) or cervical plus bilateral thoracolumbar microinjection (group E, n = 3). RESULTS: Unilateral cervical (group D, n = 3) and cervical plus thoracolumbar (group E, n = 3) microinjections to the ventral horn have been completed in ambulatory patients. One patient developed a postoperative kyphotic deformity prompting completion of a laminoplasty in subsequent patients. Another required reoperation for wound dehiscence and infection. The solitary patient with bulbar amyotrophic lateral sclerosis required perioperative reintubation. CONCLUSION: Delivery of a cellular payload to the cervical or thoracolumbar spinal cord was well tolerated by the spinal cord in this vulnerable population. This encouraging finding supports consideration of this delivery approach for neurodegenerative, oncologic, and traumatic spinal cord afflictions.

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People with amyotrophic lateral sclerosis and their caregivers: what matters most?

BMJ Supportive & Palliative Care ◽

10.1136/bmjspcare-2020-002741 ◽

2021 ◽

pp. bmjspcare-2020-002741

Author(s):

Paola Brunori ◽

Maria Grazia Celani ◽

Angelo Alberto Bignamini ◽

Marzia Carlini ◽

Rossella Papetti ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Disease Burden ◽

Anger Management ◽

Care Service ◽

Group Discussion ◽

Future Research ◽

Text File ◽

Medical Issues ◽

Research Questions ◽

Lateral Sclerosis

ObjectivesThe aim of this study is to collect the perspectives and values of people affected by amyotrophic lateral sclerosis (ALS) and their carers to offer clinicians, researchers and policymakers aspects which are precious in prioritising future research questions and reshaping care service organisations in a participatory approach.Design and settingCohort study using ALS Umbria, the electronic database in Italy.ParticipantsEleven patients and 33 carers who agreed to participate in the study were divided into six focus groups by ‘status’ (patient or carer) and by four severity levels of ‘burden of disease’.MethodsA semiquantitative analysis was undertaken. Each recorded group discussion was transcribed into text file and independently read by two psychologists and two ALS specialists to blindly identify needs, emotions and medical issues, which are the key semantic meanings expressed. Any disagreement in interpretation was resolved through consultation among authors.ResultsCarers pronounced significantly more words related to patient’s disease burden they cared. 40% of subjects expressed the need for ‘assistance’, regardless of the disease burden. ‘Anger’ alone represented more than 1/4 of all expressed emotions and was more common in patients than in carers (73% vs 36%, p=0.077). The most frequent medical issue expressed by 1/3 of participants was ‘difficulty in communication’.ConclusionThis study has given voice to the expectations of those affected by the burden of ALS. ‘Welfare assistance’, ‘anger management’ and resolution of ‘difficulties in communication’ represent issues that need to be analysed in a common prioritised research agenda with sensible and shared outcome measures to implement patient-centred medicine.

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Generation of an induced pluripotent stem cell line (UCSCi001-A) from a patient with early-onset amyotrophic lateral sclerosis carrying a FUS variant

Stem Cell Research ◽

10.1016/j.scr.2021.102461 ◽

2021 ◽

pp. 102461

Author(s):

Francesco Martello ◽

Serena Lattante ◽

Paolo Niccolò Doronzio ◽

Amelia Conte ◽

Giulia Bisogni ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Stem Cell ◽

Cell Line ◽

Early Onset ◽

Pluripotent Stem Cell ◽

Induced Pluripotent Stem Cell ◽

Stem Cell Line ◽

Induced Pluripotent ◽

Lateral Sclerosis

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Dental pulp stem cell‐derived exosomes alleviate cerebral ischaemia‐reperfusion injury through suppressing inflammatory response

Cell Proliferation ◽

10.1111/cpr.13093 ◽

2021 ◽

Author(s):

Song Li ◽

Lihua Luo ◽

Yan He ◽

Ruohan Li ◽

Yangfan Xiang ◽

...

Keyword(s):

Stem Cell ◽

Inflammatory Response ◽

Reperfusion Injury ◽

Cerebral Ischaemia ◽

Dental Pulp ◽

Ischaemia Reperfusion Injury ◽

Ischaemia Reperfusion ◽

Dental Pulp Stem Cell

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“My World Has Expanded Even Though I'm Stuck at Home”: Experiences of Individuals With Amyotrophic Lateral Sclerosis Who Use Augmentative and Alternative Communication and Social Media

American Journal of Speech-Language Pathology ◽

10.1044/2015_ajslp-15-0010 ◽

2015 ◽

Vol 24 (4) ◽

pp. 680-695 ◽

Cited By ~ 22

Author(s):

Jessica Caron ◽

Janice Light

Keyword(s):

Social Media ◽

Amyotrophic Lateral Sclerosis ◽

Augmentative And Alternative Communication ◽

Future Research ◽

Loss Of Function ◽

Alternative Communication ◽

Communication Modes ◽

Communication Needs ◽

Use Of Social Media ◽

Lateral Sclerosis

PurposeThis study aimed to expand the current understanding of how persons with amyotrophic lateral sclerosis (pALS) use augmentative and alternative communication and social media to address their communication needs.MethodAn online focus group was used to investigate the experiences of 9 pALS who use augmentative and alternative communication and social media. Questions posed to the group related to (a) current use of social media, (b) advantages of social media, (c) barriers to independent use, (d) supports to independent use, and (e) recommendations for developers, policy makers, and other pALS.ResultsParticipants primarily reported that use of social media was a beneficial tool that provided increased communication opportunities, connections to communication partners, and networks of support. Specific results are discussed with reference to the research as well as implications for practice and recommendations for future research.ConclusionsAs individuals with ALS experience loss of function, some communication modes may no longer be viable. Providing access to different modes of communication, including social media, can allow independence, participation and better quality of life.

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Antiapoptotic activity maintenance of Brain Derived Neurotrophic Factor and the C fragment of the tetanus toxin genetic fusion protein

Open Life Sciences ◽

10.2478/s11535-008-0011-z ◽

2008 ◽

Vol 3 (2) ◽

pp. 105-112 ◽

Cited By ~ 2

Author(s):

Jesús Ciriza ◽

Marcos García-Ojeda ◽

Inmaculada Martín-Burriel ◽

Cendra Agulhon ◽

Francisco Miana-Mena ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Neurotrophic Factor ◽

Tetanus Toxin ◽

Brain Derived Neurotrophic Factor ◽

Trophic Factors ◽

Low Concentrations ◽

Neuro2a Cells ◽

Genetic Fusion ◽

The Brain ◽

Lateral Sclerosis

AbstractNeurotrophic factors have been widely suggested as a treatment for multiple diseases including motorneuron pathologies, like Amyotrophic Lateral Sclerosis. However, clinical trials in which growth factors have been systematically administered to Amyotrophic Lateral Sclerosis patients have not been effective, owing in part to the short half-life of these factors and their low concentrations at target sites. A possible strategy is the use of the atoxic C fragment of the tetanus toxin as a neurotrophic factor carrier to the motorneurons. The activity of trophic factors should be tested because their genetic fusion to proteins could alter their folding and conformation, thus undermining their neuroprotective properties. For this purpose, in this paper we explored the Brain Derived Neurotrophic Factor (BDNF) activity maintenance after genetic fusion with the C fragment of the tetanus toxin. We demonstrated that BDNF fused with the C fragment of the tetanus toxin induces the neuronal survival Akt kinase pathway in mouse cortical culture neurons and maintains its antiapoptotic neuronal activity in Neuro2A cells.

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