Mesenchymal Stromal Cell Secretome for Tissue Repair

2019 ◽  
pp. 1-26
Author(s):  
Massimiliano Gnecchi ◽  
Maria Chiara Ciuffreda ◽  
Manuela Mura
Keyword(s):  
Mesenchymal Stromal Cell ◽  
Tissue Repair ◽  
Stromal Cell

scholarly journals Mitochondrial Transfer and Regulators of Mesenchymal Stromal Cell Function and Therapeutic Efficacy

2020 ◽  
Vol 8 ◽  
Author(s):  
Amina Mohammadalipour ◽  
Sandeep P. Dumbali ◽  
Pamela L. Wenzel
Keyword(s):  
Regenerative Medicine ◽  
Cancer Progression ◽  
Mesenchymal Stromal Cell ◽  
Tissue Repair ◽  
Stromal Cell ◽  
Nutrient Utilization ◽  
Metabolic Reprogramming ◽  
Mitochondrial Activity ◽  
Mitochondrial Transfer

Mesenchymal stromal cell (MSC) metabolism plays a crucial role in the surrounding microenvironment in both normal physiology and pathological conditions. While MSCs predominantly utilize glycolysis in their native hypoxic niche within the bone marrow, new evidence reveals the importance of upregulation in mitochondrial activity in MSC function and differentiation. Mitochondria and mitochondrial regulators such as sirtuins play key roles in MSC homeostasis and differentiation into mature lineages of the bone and hematopoietic niche, including osteoblasts and adipocytes. The metabolic state of MSCs represents a fine balance between the intrinsic needs of the cellular state and constraints imposed by extrinsic conditions. In the context of injury and inflammation, MSCs respond to reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs), such as damaged mitochondria and mitochondrial products, by donation of their mitochondria to injured cells. Through intercellular mitochondria trafficking, modulation of ROS, and modification of nutrient utilization, endogenous MSCs and MSC therapies are believed to exert protective effects by regulation of cellular metabolism in injured tissues. Similarly, these same mechanisms can be hijacked in malignancy whereby transfer of mitochondria and/or mitochondrial DNA (mtDNA) to cancer cells increases mitochondrial content and enhances oxidative phosphorylation (OXPHOS) to favor proliferation and invasion. The role of MSCs in tumor initiation, growth, and resistance to treatment is debated, but their ability to modify cancer cell metabolism and the metabolic environment suggests that MSCs are centrally poised to alter malignancy. In this review, we describe emerging evidence for adaptations in MSC bioenergetics that orchestrate developmental fate decisions and contribute to cancer progression. We discuss evidence and potential strategies for therapeutic targeting of MSC mitochondria in regenerative medicine and tissue repair. Lastly, we highlight recent progress in understanding the contribution of MSCs to metabolic reprogramming of malignancies and how these alterations can promote immunosuppression and chemoresistance. Better understanding the role of metabolic reprogramming by MSCs in tissue repair and cancer progression promises to broaden treatment options in regenerative medicine and clinical oncology.

Mesenchymal Stromal Cell Secretome for Tissue Repair

2020 ◽  
pp. 641-666
Author(s):  
Massimiliano Gnecchi ◽  
Maria Chiara Ciuffreda ◽  
Manuela Mura
Keyword(s):  
Mesenchymal Stromal Cell ◽  
Tissue Repair ◽  
Stromal Cell

scholarly journals Mesenchymal Stromal Cell-Derived Extracellular Vesicles Regulate the Mitochondrial Metabolism via Transfer of miRNAs

2021 ◽  
Vol 12 ◽  
Author(s):  
Claire Loussouarn ◽  
Yves-Marie Pers ◽  
Claire Bony ◽  
Christian Jorgensen ◽  
Danièle Noël
Keyword(s):  
Energy Metabolism ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Mesenchymal Stromal Cell ◽  
Tissue Repair ◽  
Stromal Cell ◽  
Target Cells ◽  
Different Types ◽  
And Oxidative Stress

Mesenchymal stromal cells (MSCs) are the most commonly tested adult progenitor cells in regenerative medicine. They stimulate tissue repair primarily through the secretion of immune-regulatory and pro-regenerative factors. There is increasing evidence that most of these factors are carried on extracellular vesicles (EVs) that are released by MSCs, either spontaneously or after activation. Exosomes and microvesicles are the most investigated types of EVs that act through uptake by target cells and cargo release inside the cytoplasm or through interactions with receptors expressed on target cells to stimulate downstream intracellular pathways. They convey different types of molecules, including proteins, lipids and acid nucleics among which, miRNAs are the most widely studied. The cargo of EVs can be impacted by the culture or environmental conditions that MSCs encounter and by changes in the energy metabolism that regulate the functional properties of MSCs. On the other hand, MSC-derived EVs are also reported to impact the metabolism of target cells. In the present review, we discuss the role of MSC-EVs in the regulation of the energy metabolism and oxidative stress of target cells and tissues with a focus on the role of miRNAs.

Sign in / Sign up

Export Citation Format

Share Document