Patient-Specific Cells for Modeling and Decoding Amyotrophic Lateral Sclerosis: Advances and Challenges

Zhao, Andong; Pan, Yu; Cai, Sa

doi:10.1007/s12015-019-09946-8

Cited by 13 publications

(29 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The model also allowed the study of gel contraction and the aim was to study in vitro the effect of muscle stretching on mRNA expression in diseased muscles cells [ 213 , 214 ]. The gold standard model that recapitulates all of the disease aspects observed in ALS would have to be a whole spinal cord organoid obtained from ALS patient-derived iPSCs [ 215 ]. Although this has not yet been developed, recent advances allowed the development of 3-D-engineered spinal cord models [ 216 , 217 ].…”

Section: The Role Of Scaffolds In Developing Regenerative Therapiementioning

confidence: 99%

Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases

Rey

Barzaghini

Nardini

et al. 2020

Cells

View full text Add to dashboard Cite

In the field of regenerative medicine applied to neurodegenerative diseases, one of the most important challenges is the obtainment of innovative scaffolds aimed at improving the development of new frontiers in stem-cell therapy. In recent years, additive manufacturing techniques have gained more and more relevance proving the great potential of the fabrication of precision 3-D scaffolds. In this review, recent advances in additive manufacturing techniques are presented and discussed, with an overview on stimulus-triggered approaches, such as 3-D Printing and laser-based techniques, and deposition-based approaches. Innovative 3-D bioprinting techniques, which allow the production of cell/molecule-laden scaffolds, are becoming a promising frontier in disease modelling and therapy. In this context, the specific biomaterial, stiffness, precise geometrical patterns, and structural properties are to be considered of great relevance for their subsequent translational applications. Moreover, this work reports numerous recent advances in neural diseases modelling and specifically focuses on pre-clinical and clinical translation for scaffolding technology in multiple neurodegenerative diseases.

show abstract

Section: The Role Of Scaffolds In Developing Regenerative Therapiementioning

confidence: 99%

Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases

Rey

Barzaghini

Nardini

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Moreover, drugs developed in these models have shown to be ineffective in humans due to interspecies differences, considering the difference between the human central nervous system and the system in animal models as an example. Thus, to improve our understanding, the establishment of patient-specific models, using regenerative medicine is crucial ( 29 , 67 ).…”

Section: Als In Vitro Modeling Platformsmentioning

confidence: 99%

“…Stem cells have great potential to proliferate and differentiate into various cells including those that are difficult to isolate from patients ( 68 , 69 ). One type of stem cell which can be used for this purpose is human embryonic stem cell (hESC) ( 29 ). They are known to be valuable tools for SOD1 mutation studies and have shown that cells with this mutation present mutation-dependent reduction in axonal length ( 70 ).…”

Section: Als In Vitro Modeling Platformsmentioning

confidence: 99%

See 1 more Smart Citation

Organ on a Chip: A Novel in vitro Biomimetic Strategy in Amyotrophic Lateral Sclerosis (ALS) Modeling

et al. 2022

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis is a pernicious neurodegenerative disorder that is associated with the progressive degeneration of motor neurons, the disruption of impulse transmission from motor neurons to muscle cells, and the development of mobility impairments. Clinically, muscle paralysis can spread to other parts of the body. Hence it may have adverse effects on swallowing, speaking, and even breathing, which serves as major problems facing these patients. According to the available evidence, no definite treatment has been found for amyotrophic lateral sclerosis (ALS) that results in a significant outcome, although some pharmacological and non-pharmacological treatments are currently applied that are accompanied by some positive effects. In other words, available therapies are only used to relieve symptoms without any significant treatment effects that highlight the importance of seeking more novel therapies. Unfortunately, the process of discovering new drugs with high therapeutic potential for ALS treatment is fraught with challenges. The lack of a broad view of the disease process from early to late-stage and insufficiency of preclinical studies for providing validated results prior to conducting clinical trials are other reasons for the ALS drug discovery failure. However, increasing the combined application of different fields of regenerative medicine, especially tissue engineering and stem cell therapy can be considered as a step forward to develop more novel technologies. For instance, organ on a chip is one of these technologies that can provide a platform to promote a comprehensive understanding of neuromuscular junction biology and screen candidate drugs for ALS in combination with pluripotent stem cells (PSCs). The structure of this technology is based on the use of essential components such as iPSC- derived motor neurons and iPSC-derived skeletal muscle cells on a single miniaturized chip for ALS modeling. Accordingly, an organ on a chip not only can mimic ALS complexities but also can be considered as a more cost-effective and time-saving disease modeling platform in comparison with others. Hence, it can be concluded that lab on a chip can make a major contribution as a biomimetic micro-physiological system in the treatment of neurodegenerative disorders such as ALS.

show abstract

“…There is no causal therapy for amyotrophic lateral sclerosis (ALS) – a rare, fatal, progressive disease that has been rapidly increasing [ 1 ] and occurs de novo in 90% [ 2 ]. The studies using iPSC-derived motor neurons revealed the complicated molecular nature of this disease related to mitochondrial dysfunction and ER stress, NF aggregate formation, hyperexcitability, and channel deficits [ 3 ]. There is still only one approved drug in Europe – riluzole, which extends survival by 3 months on average.…”

Section: Introductionmentioning

confidence: 99%

Umbilical Cord Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis: an Original Study

Barczewska

Maksymowicz

Zdolińska-Malinowska

et al. 2020

Stem Cell Rev and Rep

View full text Add to dashboard Cite

Objective Amyotrophic lateral sclerosis (ALS) is still incurable. Although different therapies can affect the health and survival of patients. Our aim is to evaluate the effect of umbilical mesenchymal stem cells administrated intrathecally to patients with amyotrophic lateral sclerosis on disability development and survival. Methods This case-control study involved 67 patients treated with Wharton’s jelly mesenchymal stem cells (WJ-MSC). The treated patients were paired with 67 reference patients from the PRO-ACT database which contains patient records from 23 ALS clinical studies (phase 2/3). Patients in the treatment and reference groups were fully matched in terms of race, sex, onset of symptoms (bulbar/spinal), FT9 disease stage at the beginning of therapy and concomitant amyotrophic lateral sclerosis medications. Progression rates prior to treatment varied within a range of ± 0.5 points. All patients received three intrathecal injections of Wharton’s jelly-derived mesenchymal stem cells every two months at a dose of 30 × 10 6 cells. Patients were assessed using the ALSFRS-R scale. Survival times were followed-up until March 2020. Results Median survival time increased two-fold in all groups. In terms of progression, three response types measured in ALSFRS-R were observed: decreased progression rate ( n = 21, 31.3%), no change in progression rate ( n = 33, 49.3%) and increased progression rate ( n = 13, 19.4%). Risk-benefit ratios were favorable in all groups. No serious adverse drug reactions were observed. Interpretation Wharton’s jelly-derived mesenchymal stem cells therapy is safe and effective in some ALS patients, regardless of the clinical features and demographic factors excluding sex. The female sex and a good therapeutic response to the first administration are significant predictors of efficacy following further administrations. Graphical Abstract Medical therapeutic experiment with retrospective case-control analyses Electronic supplementary material The online version of this article (10.1007/s12015-020-10016-7) contains supplementary material, which is available to authorized users.

show abstract

Patient-Specific Cells for Modeling and Decoding Amyotrophic Lateral Sclerosis: Advances and Challenges

Cited by 13 publications

References 120 publications

Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases

Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases

Organ on a Chip: A Novel in vitro Biomimetic Strategy in Amyotrophic Lateral Sclerosis (ALS) Modeling

Umbilical Cord Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis: an Original Study

Contact Info

Product

Resources

About