Stem Cells in Clinical Trials on Neurological Disorders: Trends in Stem Cells Origins, Indications, and Status of the Clinical Trials

Namiot, Eugenia D.; Niemi, Jenni Viivi Linnea; Chubarev, Vladimir N.; Tarasov, Vadim V.; Schiöth, Helgi B.

doi:10.3390/ijms231911453

Cited by 16 publications

(5 citation statements)

References 60 publications

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“…This breakthrough has allowed for the study and treatment of genetic diseases, particularly neurological disorders [ 14 ]. Clinical trials of the application of stem cells as a therapeutic approach to tackle various neurological disorders, encompassing conditions such as injuries affecting the brain, spinal cord and peripheral nerves, are now being performed [ 15 ]. Also, stem cell-derived motor neurons have aided in the discovery of amyotrophic lateral sclerosis drugs [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Single-cell RNA-seq data analysis reveals functionally relevant biomarkers of early brain development and their regulatory footprints in human embryonic stem cells (hESCs)

Alamin,

Humaira Sultana,

Babarinde

et al. 2024

Briefings in Bioinformatics

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The complicated process of neuronal development is initiated early in life, with the genetic mechanisms governing this process yet to be fully elucidated. Single-cell RNA sequencing (scRNA-seq) is a potent instrument for pinpointing biomarkers that exhibit differential expression across various cell types and developmental stages. By employing scRNA-seq on human embryonic stem cells, we aim to identify differentially expressed genes (DEGs) crucial for early-stage neuronal development. Our focus extends beyond simply identifying DEGs. We strive to investigate the functional roles of these genes through enrichment analysis and construct gene regulatory networks to understand their interactions. Ultimately, this comprehensive approach aspires to illuminate the molecular mechanisms and transcriptional dynamics governing early human brain development. By uncovering potential links between these DEGs and intelligence, mental disorders, and neurodevelopmental disorders, we hope to shed light on human neurological health and disease. In this study, we have used scRNA-seq to identify DEGs involved in early-stage neuronal development in hESCs. The scRNA-seq data, collected on days 26 (D26) and 54 (D54), of the in vitro differentiation of hESCs to neurons were analyzed. Our analysis identified 539 DEGs between D26 and D54. Functional enrichment of those DEG biomarkers indicated that the up-regulated DEGs participated in neurogenesis, while the down-regulated DEGs were linked to synapse regulation. The Reactome pathway analysis revealed that down-regulated DEGs were involved in the interactions between proteins located in synapse pathways. We also discovered interactions between DEGs and miRNA, transcriptional factors (TFs) and DEGs, and between TF and miRNA. Our study identified 20 significant transcription factors, shedding light on early brain development genetics. The identified DEGs and gene regulatory networks are valuable resources for future research into human brain development and neurodevelopmental disorders.

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Section: Introductionmentioning

confidence: 99%

Single-cell RNA-seq data analysis reveals functionally relevant biomarkers of early brain development and their regulatory footprints in human embryonic stem cells (hESCs)

Alamin,

Humaira Sultana,

Babarinde

et al. 2024

Briefings in Bioinformatics

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“…Many studies have reported that MSCs could be isolated from adipose tissue [ 14 , 17 ]. It has been shown that adipose MSCs (AMSCs) with multipotentiality give rise to adipocytes, neurocytes, chondrocytes, myocytes, and osteoblasts cell lineages [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells

Yang

Fan

Liu

et al. 2023

Stem Cell Rev and Rep

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Mesenchymal stem cells (MSCs) are regarded as highly promising cells for allogeneic cell therapy, owing to their multipotent nature and ability to display potent and varied functions in different diseases. The functions of MSCs, including native immunomodulation, high self-renewal characteristic, and secretory and trophic properties, can be employed to improve the immune-modulatory functions in diseases. MSCs impact most immune cells by directly contacting and/or secreting positive microenvironmental factors to influence them. Previous studies have reported that the immunomodulatory role of MSCs is basically dependent on their secretion ability from MSCs. This review discusses the immunomodulatory capabilities of MSCs and the promising strategies to successfully improve the potential utilization of MSCs in clinical research. Graphical Abstract

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“…The regenerative potential of mesenchymal stem cells of different origins has been studied and contrasted by numerous research groups (40)(41)(42). The source from which organ-specific mesenchymal stem cells have traditionally been extracted is bone marrow.…”

Section: Introductionmentioning

confidence: 99%

Human Placenta-Derived Mesenchymal Stem Cells Stimulate Neuronal Regeneration By Promoting Axon Growth And Restoring Neuronal Activity

de Laorden,

Simón,

Milla

et al. 2023

Preprint

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Cell therapy is a cutting-edge medical approach that involves the use of cells to treat various diseases and conditions. It harnesses the remarkable regenerative and reparative abilities of cells to restore or replace damaged tissues and promote healing. In the last decades, mesenchymal stem cells have become the cornerstone of cellular therapy due to their unique characteristics. Specifically human placenta-derived mesenchymal stem cells (hPMSCs) are highlighted for their unique features including ease to isolate, non-invasive techniques for large scale cell production, significant immunomodulatory capacity, and high ability to migrate to injuries. Researchers are exploring innovative techniques to overcome the low regenerative capacity of Central Nervous System (CNS) neurons, with one promising avenue being the development of tailored mesenchymal stem cell therapies capable of promoting neural repair and recovery. In this context, we have evaluated hPMSCs as candidate for CNS lesion regeneration using a skillful co-culture model system. Indeed, we have demonstrated the hPMSCs ability to stimulate damaged rat-retina neurons regeneration by promoting axon growth and restoring neuronal activity both under normoxia and hypoxia conditions. With our model we have obtained neuronal regeneration values of 10-12% and axonal length per neuron rates of 19.99, μm/neuron. To assess whether the regenerative capabilities of hPMSCs are contact-dependent effects or it is mediated through paracrine mechanisms, we carried out transwell co-culture and conditioned medium experiments confirming the role of secreted factors in axonal regeneration. It was found that hPMSCs produce brain derived, nervegrowth factors (BDNF, NGF) and Neurotrophin-3, involved in the process of neuronal regeneration and restoration of their physiological activity of neurons. The capability to access axonal physiology is crucial for studying information processing among neurons in healthy and diseased states. We confirm the success of our treatment using the patch clamp technique to study ionic currents in individual isolated living cells, confirming that in our model the regenerated neurons are electrophysiologically active. The outcomes of our neuronal regeneration studies, combined with the axon-regenerating capabilities exhibited by mesenchymal stem cells derived from the placenta, present a hopeful outlook for the potential therapeutic application of hPMSCs in the treatment of neurological disorders.

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Stem Cells in Clinical Trials on Neurological Disorders: Trends in Stem Cells Origins, Indications, and Status of the Clinical Trials

Cited by 16 publications

References 60 publications

Single-cell RNA-seq data analysis reveals functionally relevant biomarkers of early brain development and their regulatory footprints in human embryonic stem cells (hESCs)

Single-cell RNA-seq data analysis reveals functionally relevant biomarkers of early brain development and their regulatory footprints in human embryonic stem cells (hESCs)

Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells

Human Placenta-Derived Mesenchymal Stem Cells Stimulate Neuronal Regeneration By Promoting Axon Growth And Restoring Neuronal Activity

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