Exosomes/miRNAs as mediating cell-based therapy of stroke

Abstract

Cell-based therapy, e.g., multipotent mesenchymal stromal cell (MSC) treatment, shows promise for the treatment of various diseases. The strong paracrine capacity of these cells and not their differentiation capacity, is the principal mechanism of therapeutic action. MSCs robustly release exosomes, membrane vesicles (~30–100 nm) originally derived in endosomes as intraluminal vesicles, which contain various molecular constituents including proteins and RNAs from maternal cells. Contained among these constituents, are small non-coding RNA molecules, microRNAs (miRNAs), which play a key role in mediating biological function due to their prominent role in gene regulation. The release as well as the content of the MSC generated exosomes are modified by environmental conditions. Via exosomes, MSCs transfer their therapeutic factors, especially miRNAs, to recipient cells, and therein alter gene expression and thereby promote therapeutic response. The present review focuses on the paracrine mechanism of MSC exosomes, and the regulation and transfer of exosome content, especially the packaging and transfer of miRNAs which enhance tissue repair and functional recovery. Perspectives on the developing role of MSC mediated transfer of exosomes as a therapeutic approach will also be discussed.

Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell‐free therapy

“…Different isolation or purification methods can also yield heterogeneous MSC-exosomes, making it difficult to compare proteomic studies between them. Second, the composition of exosomes is closely associated with the cellular health and condition of the secreting cells as different molecular signatures are found between exosomes derived from healthy, ageing, and diseased cells or their growth environment(s) [36–38]. Nevertheless, considering the complex production pathway, exosomes generated from MSCs in a well-defined culture environment could be a powerful therapeutic agent by themselves for cell-free therapy and circumvent the issue of immune rejection that can occur in live cell-based therapies.…”

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

“…MSCs have shown promise in the field of regenerative medicine, since exogenously administered MSCs target injured tissue, interact with brain parenchymal cells, and promote neurorestoration and recovery of neurological function after brain injuries [178,191,204,205]. Despite the differentiation capacity of MSCs, the principal mechanism of their therapeutic action seems to be a robust paracrine capacity, related to their soluble factors as well as generation and release of microvesicles and exosomes [178,205].…”

“…Despite the differentiation capacity of MSCs, the principal mechanism of their therapeutic action seems to be a robust paracrine capacity, related to their soluble factors as well as generation and release of microvesicles and exosomes [178,205]. Extracellular vesicles (EVs) are membrane bound entities that transmit signals between cells via all cells and are found in all body fluids [206,207].…”

Is Immunomodulation a Principal Mechanism Underlying How Cell-Based Therapies Enhance Stroke Recovery?

“…Indeed, the secretomes of cellular therapies have become an active area of research in the hopes of identifying the factors produced by cell therapies that are critical to their effects. Many cell therapies also release microvesicles such as exosomes, which themselves may penetrate and re-engineer the biological properties of target tissues [45][46][47].…”