Characterization of Mesenchymal Stem Cells Derived from Patients with Cerebellar Ataxia: Downregulation of the Anti-Inflammatory Secretome Profile

Kim, Jong‐Heon; Han, Jin; Seo, Donggun; Yoon, Jong Hyuk; Yoon, Dongyeong; Hong, Ji Won; Kim, Sang Ryong; Kim, Min Sung; Lee, Tae Yong; Kim, Kyung Suk; Ko, Pan‐Woo; Lee, Ho‐Won; Suk, Kyoungho

doi:10.3390/cells9010212

Cited by 11 publications

(5 citation statements)

References 68 publications

(42 reference statements)

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“…Two studies in humans have also shown that autologous MSC therapy via intra-arterial and intravenous [ 7 ] or intrathecal [ 8 ] routes could delay the progression of cerebellar dysfunction and improve functional status. Several mechanisms of MSC therapy for cerebellar ataxia have been proposed such as the mitigation of neuronal apoptosis, the regeneration of neurons and anti-inflammatory reactions [ 9 , 10 ]. In addition, a recent study has found that the growth rate and expression of the neuroprotective factors of MSCs in patients with cerebellar ataxia were decreased as opposed to MSCs in healthy people [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several mechanisms of MSC therapy for cerebellar ataxia have been proposed such as the mitigation of neuronal apoptosis, the regeneration of neurons and anti-inflammatory reactions [ 9 , 10 ]. In addition, a recent study has found that the growth rate and expression of the neuroprotective factors of MSCs in patients with cerebellar ataxia were decreased as opposed to MSCs in healthy people [ 10 ]. Therefore, it can be suggested that allogeneic MSC therapy via the intrathecal route in this patient might induce a neuroprotective effect, which, in our case, could be represented by the improved K-SARA scores.…”

Section: Discussionmentioning

confidence: 99%

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Human Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Cerebellar Ataxia: A Case Report

Park

Kang

et al. 2021

Medicina

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To date, there is no curable treatment option for non-hereditary degenerative cerebellar ataxia. Here we report the case of a patient with sporadic adult-onset ataxia (SAOA) who underwent allogeneic bone marrow-derived mesenchymal stem cell (MSC) therapy via the intrathecal route. A 60-year-old male patient visited our clinic complaining of progressive gait disturbance that commenced two years ago. Upon neurologic examination, the patient exhibited limb dysmetria and gait ataxia. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy whereas the autonomic function test was normal. The patient was diagnosed with SAOA. The medications that were initially prescribed had no significant effects on the course of this disease and the symptoms deteriorated progressively. At the age of 64, the patient was treated with allogeneic bone marrow-derived MSC therapy. The subsequent K-SARA (Korean version of the Scale for the Assessment and Rating of Ataxia) scores demonstrated a distinct improvement up until 10 months post-administration. No adverse events were reported. The improved post-treatment K-SARA scores may suggest that the MSC therapy can have a neuroprotective effect and that stem cell therapy may serve as a potential therapeutic option for degenerative cerebellar ataxia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Cerebellar Ataxia: A Case Report

Park

Kang

et al. 2021

Medicina

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“…The infusion of aged MSCs or their EVs led to impaired immunomodulatory actions ( Yu et al, 2014 ; Huang et al, 2019 ) or even deleterious effects in disease models ( Lee and Yu, 2020 ). Moreover, certain diseases can alter MSC niche or cell metabolism, thus promoting a negative impact on their therapeutic ability when they are harvested for either autologous or allogeneic infusion ( Silva et al, 2014 ; Antebi et al, 2018 ; Kim et al, 2020 ; Antunes et al, 2021 ). To identify MSCs of potential clinical use, a number of reference biomarkers should be validated for donor selection and thus the number of batches of good donors should be maximized.…”

Section: Translational Challenges and Future Directionsmentioning

confidence: 99%

Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases

Lopes‐Pacheco

Rocco

2023

Front. Pharmacol.

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Respiratory diseases remain a major health concern worldwide because they subject patients to considerable financial and psychosocial burdens and result in a high rate of morbidity and mortality. Although significant progress has been made in understanding the underlying pathologic mechanisms of severe respiratory diseases, most therapies are supportive, aiming to mitigate symptoms and slow down their progressive course but cannot improve lung function or reverse tissue remodeling. Mesenchymal stromal cells (MSCs) are at the forefront of the regenerative medicine field due to their unique biomedical potential in promoting immunomodulation, anti-inflammatory, anti-apoptotic and antimicrobial activities, and tissue repair in various experimental models. However, despite several years of preclinical research on MSCs, therapeutic outcomes have fallen far short in early-stage clinical trials for respiratory diseases. This limited efficacy has been associated with several factors, such as reduced MSC homing, survival, and infusion in the late course of lung disease. Accordingly, genetic engineering and preconditioning methods have emerged as functional enhancement strategies to potentiate the therapeutic actions of MSCs and thus achieve better clinical outcomes. This narrative review describes various strategies that have been investigated in the experimental setting to functionally potentiate the therapeutic properties of MSCs for respiratory diseases. These include changes in culture conditions, exposure of MSCs to inflammatory environments, pharmacological agents or other substances, and genetic manipulation for enhanced and sustained expression of genes of interest. Future directions and challenges in efficiently translating MSC research into clinical practice are discussed.

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“…Another strongly suggested problem is the individual difference between MSCs based on the variable backgrounds from donor to donor. Moreover, MSCs from patients with specific diseases show downregulation of cell function such as an anti-inflammatory secretome, reflecting inferior therapeutic capability [11]. To overcome the limitation, disease-specific MSC selection before the application has been required.…”

Section: Msc Selectionmentioning

confidence: 99%

Functional enhancement strategies for immunomodulation of mesenchymal stem cells and their therapeutic application

Lee

Kang

2020

Stem Cell Res Ther

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Mesenchymal stem cells (MSCs) have recently been considered a promising alternative treatment for diverse immune disorders due to their unique biomedical potentials including the immunomodulatory property and ability to promote tissue regeneration. However, despite many years of pre-clinical studies in the research field, results from clinical trials using these cells have been diverse and conflicting. This discrepancy is caused by several factors such as poor engraftment, low survival rate, and donor-dependent variation of the cells. Enhancement of consistency and efficacy of MSCs remains a challenge to overcome the current obstacles to MSC-based therapy and subsequently achieve an improved therapeutic outcome. In this review, we investigated function enhancement strategies by categorizing as preconditioning, genetic manipulation, usage of supportive materials, and co-administration with currently used drugs. Preconditioning prior to MSC application makes up a large proportion of improvement strategies and preconditioning reagents include bioactive substances (cytokines, growth factors, and innate immune receptor agonists), hypoxia, and modification in culture method. With the piled results from previous studies using each method, disease- or patient-specific therapy has become more important than ever. On the other hand, genetic manipulation targeting therapeutic-associated factors or co-administration of biocompatible materials has also arisen as other therapeutic strategies. Thus, we summarized several specialized tactics by analyzing up-to-date results in the field and proposed some promising enhancement methods to improve the clinical outcomes for MSC therapy.

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Characterization of Mesenchymal Stem Cells Derived from Patients with Cerebellar Ataxia: Downregulation of the Anti-Inflammatory Secretome Profile

Cited by 11 publications

References 68 publications

Human Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Cerebellar Ataxia: A Case Report

Human Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Cerebellar Ataxia: A Case Report

Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases

Functional enhancement strategies for immunomodulation of mesenchymal stem cells and their therapeutic application

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