Stem cell secretome as a new booster for regenerative medicine

Xia, Jufeng; Minamino, Shuichi; Kuwabara, Kazuma; Arai, Shunichi

doi:10.5582/bst.2019.01226

Cited by 62 publications

(63 citation statements)

References 66 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar effect was observed when we used supernatants generated by exposing MIAMI cells to CQ and, to much lesser extent, TX, although interpretation of the data is further complicated because CQ alone had a strong suppressive effect on CD4+ T cell proliferation. This CQ-enhanced MIAMI cell secretome-mediated decrease in activated CD4+ T cell proliferation could be explained in part by CQ-mediated stimulation of exosome secretion observed in other cells [44], and MSC-derived exosomes have been shown to possess immunomodulatory properties [45, 46]. Altogether, these results suggested that both TX and CQ enhance immunoregulatory capacity of MIAMI cells in vitro via multiple parallel mechanisms.…”

Section: Discussionmentioning

confidence: 94%

Combination therapies enhance immunoregulatory properties of MIAMI cells

et al. 2019

View full text Add to dashboard Cite

Background: Mesenchymal stromal cells (MSCs), adult stromal cells most commonly isolated from bone marrow (BM), are being increasingly utilized in various therapeutic applications including tissue repair via immunomodulation, which is recognized as one of their most relevant mechanism of action. The promise of MSCbased therapies is somewhat hindered by their apparent modest clinical benefits, highlighting the need for approaches that would increase the efficacy of such therapies. Manipulation of cellular stress-response mechanism(s) such as autophagy, a catabolic stress-response mechanism, with small molecules prior to or during MSC injection could improve MSCs' therapeutic efficacy. Unfortunately, limited information exists on how manipulation of autophagy affects MSCs' response to inflammation and subsequent immunoregulatory properties. Methods: In this study, we exposed BM-MSC precursor cells, "marrow-isolated adult multilineage inducible" (MIAMI) cells, to autophagy modulators tamoxifen (TX) or chloroquine (CQ), together with IFN-γ. Exposed cells then underwent RNA sequencing (RNAseq) to determine the effects of TX or CQ co-treatments on cellular response to IFN-γ at a molecular level. Furthermore, we evaluated their immunoregulatory capacity using activated CD4+ T cells by analyzing T cell activation marker CD25 and the percentage of proliferating T cells after co-culturing the cells with MIAMI cells treated or not with TX or CQ. Results: RNAseq data indicate that the co-treatments alter both mRNA and protein levels of key genes responsible for MSCs' immune-regulatory properties. Interestingly, TX and CQ also altered some of the microRNAs targeting such key genes. In addition, while IFN-γ treatment alone increased the surface expression of PD-L1 and secretion of IDO, this increase was further enhanced with TX. An improvement in MIAMI cells' ability to decrease the activation and proliferation of T cells was also observed with TX, and to a lesser extent, CQ co-treatments. Conclusion: Altogether, this work suggests that both TX and CQ have a potential to enhance MIAMI cells' immunoregulatory properties. However, this enhancement is more pronounced with TX co-treatment.

show abstract

Section: Discussionmentioning

confidence: 94%

Combination therapies enhance immunoregulatory properties of MIAMI cells

et al. 2019

View full text Add to dashboard Cite

show abstract

“…52 It is well known that exosomal miRNAs mediate many functions of exosomes such as cell proliferation and differentiation as well as inhibition of cell apoptosis. 53,54 Hui Jing et al 55 showed that miR-381-enrich small extracellular vesicle (sEV) promotes stem cell chondrogenesis in vitro. They obtained miR-381-enrich sEV by culturing human umbilical cord mesenchymal stem cells (hUCMSCs) in a medium containing Kartogenin (KGN).…”

Section: The In Vitro Chondrog Eni C P Otential Of E Vsmentioning

confidence: 99%

Extracellular Vesicles in chondrogenesis and Cartilage regeneration

Zhao

Cheng

Zhou

et al. 2021

J Cellular Molecular Medi

View full text Add to dashboard Cite

Cartilage is a hydrated tissue with no vascular and neural networks.They are divided into three major groups: hyaline, fibrous and elastic cartilages. Hyaline cartilage is the most frequent form and is found in synovial joints, ribs, nose, trachea, bronchi, etc 1 The main roles of this articular hyaline cartilage are to tolerate bone load and forming a lubricant environment to enable joint movement. 2 Extracellular matrix (ECM) synthesized by chondrocytes constitutes the main part of each cartilage. Collagen type II is the most frequent ECM molecule in hyaline cartilage and accounts for 90%-95% of total collagen molecules. 3,4 Collagen II forms filamentous structures with collagen IX, responsible for cartilage tensile and shear stress. Proteoglycans, such as aggrecan, and glycosaminoglycans (GAG), such as chondroitin sulphate, are the other components of the articular cartilage ECM. 5,6 The integrity of ECM is vital for the normal function of cartilage. Therefore, changes in ECM elements and composition are the main feature of cartilage diseases. 7

show abstract

“…Cells communicate with each other by intercellular contacts and paracrine secretion of molecules [4]. Notably, several studies showed that stem cells trigger tissue repair due to their ability to secrete molecules with a beneficial impact on the damaged tissue, rather than to their capacity to differentiate into the required differentiated cells [87]. These secreted factors are referred to as cell secretome and include growth factors, cytokines, chemokines and exosomes [4,88] found in the cell culture medium (conditioned medium).…”

Section: Oxydative-signaling Of Nsc-derived Secretomementioning

confidence: 99%

Oxidative-Signaling in Neural Stem Cell-Mediated Plasticity: Implications for Neurodegenerative Diseases

2021

View full text Add to dashboard Cite

The adult mammalian brain is capable of generating new neurons from existing neural stem cells (NSCs) in a process called adult neurogenesis. This process, which is critical for sustaining cognition and mental health in the mature brain, can be severely hampered with ageing and different neurological disorders. Recently, it is believed that the beneficial effects of NSCs in the injured brain relies not only on their potential to differentiate and integrate into the preexisting network, but also on their secreted molecules. In fact, further insight into adult NSC function is being gained, pointing to these cells as powerful endogenous “factories” that produce and secrete a large range of bioactive molecules with therapeutic properties. Beyond anti-inflammatory, neurogenic and neurotrophic effects, NSC-derived secretome has antioxidant proprieties that prevent mitochondrial dysfunction and rescue recipient cells from oxidative damage. This is particularly important in neurodegenerative contexts, where oxidative stress and mitochondrial dysfunction play a significant role. In this review, we discuss the current knowledge and the therapeutic opportunities of NSC secretome for neurodegenerative diseases with a particular focus on mitochondria and its oxidative state.

show abstract

Stem cell secretome as a new booster for regenerative medicine

Cited by 62 publications

References 66 publications

Combination therapies enhance immunoregulatory properties of MIAMI cells

Combination therapies enhance immunoregulatory properties of MIAMI cells

Extracellular Vesicles in chondrogenesis and Cartilage regeneration

Oxidative-Signaling in Neural Stem Cell-Mediated Plasticity: Implications for Neurodegenerative Diseases

Contact Info

Product

Resources

About