Combination therapies enhance immunoregulatory properties of MIAMI cells

Autor: Leonor Sarria, Paul C. Schiller, Vladimir Beljanski, Fiorella Rossi, Hunter Noren, Lubov Nathanson
Jazyk: angličtina
Rok vydání: 2019
Předmět:
CD4-Positive T-Lymphocytes
Mesenchymal stromal cells
Gene Expression
Medicine (miscellaneous)
Lymphocyte Activation
B7-H1 Antigen
IDO
0302 clinical medicine
lcsh:QD415-436
IL-2 receptor
0303 health sciences
lcsh:R5-920
Chloroquine
3. Good health
medicine.anatomical_structure
030220 oncology & carcinogenesis
Molecular Medicine
medicine.symptom
Stem cell
lcsh:Medicine (General)
PD-L1
Stromal cell
Inflammation
Biology
Biochemistry
Genetics and Molecular Biology (miscellaneous)
lcsh:Biochemistry
Interferon-gamma
03 medical and health sciences
medicine
Autophagy
Humans
Indoleamine-Pyrrole 2
3
-Dioxygenase
Cell Proliferation
030304 developmental biology
Interleukin-6
Research
Mesenchymal stem cell
Immunoregulation
Mesenchymal Stem Cells
Cell Biology
Coculture Techniques
MicroRNAs
Tamoxifen
Leukocytes
Mononuclear
biology.protein
Cancer research
Bone marrow
Combination therapies
Zdroj: Stem Cell Research & Therapy, Vol 10, Iss 1, Pp 1-13 (2019)
Stem Cell Research & Therapy
ISSN: 1757-6512
Popis: 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 MSC-based 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.
Databáze: OpenAIRE
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