Abstract

Mesenchymal stem cells (MSCs) are self-renewing cells found in almost all postnatal organs and tissues in the perivascular region. These cells present multiple characteristics that make them candidates to be applied in cell therapy for neurodegenerative diseases, such as their secretory action, migration to the lesion area, and immunomodulatory potential. These cells have a high capacity for mesodermal differentiation; however, numerous studies have shown that MSCs can also differentiate into neurons. However, despite positive results in multiple trials in which undifferentiated MSCs transplanted into animal models of neurodegenerative diseases, some studies suggest that the therapeutic effects obtained are enhanced by the use of MSCs differentiated towards the neuronal lineage before transplant. In this sense, there are several methods to induce in vitro reprogramming of MSCs towards the neuronal lineage, including chemical substances, growth factors, cocultures with neural lineage cells, transfection of genes, miRNAs, etc., and small molecules stand out. Therefore, this article compares multiple experimental tests in which these inducers promote neuronal differentiation of MSCs and identify those methods that originate an optimal neuronal differentiation. The analysis includes the percentage of differentiation, maturation, expression of neuronal markers, functionality, and cell survival considering the intrinsic characteristics of the MSCs used as the tissue of origin and the species from which they were isolated.

Highlights

  • Mesenchymal stem cells (MSC), known as multipotent mesenchymal stromal cells, are present in almost all postnatal organs and tissues, in the perivascular region [1]

  • Despite positive results in multiple trials in which undifferentiated MSCs transplanted into animal models of neurodegenerative diseases, some studies suggest that the therapeutic effects obtained are enhanced by the use of MSCs differentiated towards the neuronal lineage before transplant

  • Cultured cells must present similar criteria to be considered as MSC, regardless of the site from which they are obtained; some differences have been found regarding the proliferative capacity and expandability among some MSC depending on their origin, for example, bone marrow and adipose tissue MSC have greater culture efficacy than umbilical cord MSC, but the latter has more significant expansion potential compared to other cell sources [15]

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Summary

Introduction

Mesenchymal stem cells (MSC), known as multipotent mesenchymal stromal cells, are present in almost all postnatal organs and tissues, in the perivascular region [1] These cells are characterized by a spindle-shaped morphology with an elongated central nucleus and contain 2 to 3 nucleolus. In vitro reprogramming of MSCs towards the neuronal lineage can be carried out using different methodologies with different inducers, such as chemical substances, growth factors, co-cultivation with neural lineage cells, gene transfection miRNA, and chemicals called small molecules. These methodologies show considerable variations in terms of efficiency of differentiation. The analysis will identify an optimal neuronal differentiation method with reasonable differentiation rate, maturation, expression of neuronal markers, functionality, and cell survival considering the intrinsic characteristics of the MSCs used as the tissue of origin and the species from which they were isolated

MSC History
Multipotency of MSC
Function and Properties of MSC
Competitive Advantages of MSC
MSC and Nervous System Diseases
Chemical Compounds
Antioxidants
Chemicals That Increase cAMP Levels
Chromatin Modifiers
Growth Factors
10. Coculture
11. Gene Transfection
12. Micro-RNA
13. Small Molecules
14. Retinoic Acid
15. Advantages and Disadvantages of Multiple Differentiation Protocols
The factors that promote differentiation are not
Most assays generate neurons with
Findings
16. Conclusion
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