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Article ; Online: Mesenchymal stem cell therapy for immune-modulation: the donor, the recipient, and the drugs in-between.

Nemeth, Krisztian

2014 Volume 23, Issue 9, Page(s) 625–628

Abstract: Adoptive transfer of cultured bone marrow stromal cells (mesenchymal stem cells also known as MSCs) is a promising new way to aid tissue regeneration and treat a wide variety of diseases where regulation of inflammatory responses is derailed. Although ... ...

Abstract	Adoptive transfer of cultured bone marrow stromal cells (mesenchymal stem cells also known as MSCs) is a promising new way to aid tissue regeneration and treat a wide variety of diseases where regulation of inflammatory responses is derailed. Although significant advances have been made in the field, pinpointing important mechanistic details about how MSCs function in vitro and in vivo, there are still many unanswered questions that need to be addressed before welcoming MSCs in the therapeutic arsenal of immune mediated diseases. In this viewpoint, we highlight and discuss a few factors that we believe are critical in terms of therapeutic success employing cultured MSCs. Selecting the right donor population, choosing the best culture conditions and picking the patient population that is most likely to give a favourable therapeutic response is just as important as considering interactions between MSCs and the combination of drugs in the recipient's body. Given the complexity of MSC-host interactions, it is also imperative to develop screening tools that account for as many variables as possible and predict precisely the in vivo response rates before MSCs enter the body. To achieve this, a multidisciplinary approach is required with comprehensive knowledge of basic MSC biology, immunology, pharmacology and good clinical practice.
MeSH term(s)	Adoptive Transfer/methods ; Humans ; Immune System Diseases/immunology ; Immune System Diseases/therapy ; Immunosuppressive Agents/therapeutic use ; Immunotherapy, Adoptive/methods ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stromal Cells/drug effects ; Mesenchymal Stromal Cells/immunology ; Regeneration/immunology ; Skin Diseases/immunology ; Skin Diseases/therapy ; Tissue Donors
Chemical Substances	Immunosuppressive Agents
Language	English
Publishing date	2014-09
Publishing country	Denmark
Document type	Journal Article ; Review
ZDB-ID	1130936-2
ISSN	1600-0625 ; 0906-6705
ISSN (online)	1600-0625
ISSN	0906-6705
DOI	10.1111/exd.12459
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Zs.A 3508: Show issues

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Article: Determination of Bile Acids in Canine Biological Samples: Diagnostic Significance.

Németh, Krisztián / Sterczer, Ágnes / Kiss, Dávid Sándor / Lányi, Réka Katalin / Hemző, Vivien / Vámos, Kriszta / Bartha, Tibor / Buzás, Anna / Lányi, Katalin

Metabolites

2024 Volume 14, Issue 4

Abstract: The comprehensive examination of bile acids is of paramount importance across various fields of health sciences, influencing physiology, microbiology, internal medicine, and pharmacology. While enzymatic reaction-based photometric methods remain ... ...

Abstract	The comprehensive examination of bile acids is of paramount importance across various fields of health sciences, influencing physiology, microbiology, internal medicine, and pharmacology. While enzymatic reaction-based photometric methods remain fundamental for total BA measurements, there is a burgeoning demand for more sophisticated techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) for comprehensive BA profiling. This evolution reflects a need for nuanced diagnostic assessments in clinical practice. In canines, a BA assessment involves considering factors, such as food composition, transit times, and breed-specific variations. Multiple matrices, including blood, feces, urine, liver tissue, and gallbladder bile, offer insights into BA profiles, yet interpretations remain complex, particularly in fecal analysis due to sampling challenges and breed-specific differences. Despite ongoing efforts, a consensus regarding optimal matrices and diagnostic thresholds remains elusive, highlighting the need for further research. Emphasizing the scarcity of systematic animal studies and underscoring the importance of ap-propriate sampling methodologies, our review advocates for targeted investigations into BA alterations in canine pathology, promising insights into pathomechanisms, early disease detection, and therapeutic avenues.
Language	English
Publishing date	2024-03-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo14040178
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Article ; Online: Recognition of Alkaptonuria During Mohs Micrographic Surgery.

Nemeth, Krisztian / Tolkachjov, Stanislav N

Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.

2018 Volume 45, Issue 9, Page(s) 1194–1195

MeSH term(s)	Aged ; Alkaptonuria/diagnosis ; Alkaptonuria/pathology ; Frozen Sections ; Humans ; Incidental Findings ; Male ; Melanoma/surgery ; Mohs Surgery ; Skin Neoplasms/surgery
Language	English
Publishing date	2018-09-10
Publishing country	United States
Document type	Case Reports ; Letter
ZDB-ID	1227586-4
ISSN	1524-4725 ; 1076-0512
ISSN (online)	1524-4725
ISSN	1076-0512
DOI	10.1097/DSS.0000000000001671
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Zs.A 1212: Show issues

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Article ; Online: Origin of stem cells in the BM niche: new clues from mastocytosis.

Nemeth, Krisztian / Mezey, Eva

Blood

2016 Volume 127, Issue 6, Page(s) 670–672

MeSH term(s)	Amino Acid Substitution ; Bone Marrow Cells/pathology ; Female ; Humans ; Male ; Mastocytosis, Systemic/genetics ; Mastocytosis, Systemic/pathology ; Mesenchymal Stem Cells/pathology ; Proto-Oncogene Proteins c-kit/genetics
Chemical Substances	Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
Language	English
Publishing date	2016-02-10
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2015-12-686626
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Article ; Online: Mesenchymal stem cells and infectious diseases: Smarter than drugs.

Mezey, Éva / Nemeth, Krisztián

Immunology letters

2015 Volume 168, Issue 2, Page(s) 208–214

Abstract: After bone marrow stromal cells (BMSCs also known as mesenchymal stem cells of bone marrow origin) were used successfully to treat graft versus host disease in a single human subject [1], many investigators studied the immune-suppressive properties of ... ...

Abstract	After bone marrow stromal cells (BMSCs also known as mesenchymal stem cells of bone marrow origin) were used successfully to treat graft versus host disease in a single human subject [1], many investigators studied the immune-suppressive properties of BMSCs and later adipose tissue derived MSCs (AMSC). The field has expanded significantly and there are many ongoing clinical trials that are trying to exploit the amazing abilities of MSCs from many tissues to regulate the immune system. In addition to "supervising" cells of the innate immune system, MSCs have also been shown to have anti-microbial properties. They appear to make molecules with direct effects on bacteria. Many questions about MSCs remain, however. We still need to determine how to isolate subpopulations of cells with specific immunomodulatory or antibacterial actions from the heterogeneous pool of cultured BMSCs. We need to find ways to prime cells to improve their immune regulatory activities, and while we have some ideas about mechanisms that underlie MSC/immune cell interactions, there is still much to discover before we can take full advantage of the regulatory abilities of MSCs to treat human diseases.
MeSH term(s)	Adaptive Immunity/immunology ; Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/immunology ; Bone Marrow Cells/metabolism ; Communicable Diseases/immunology ; Communicable Diseases/microbiology ; Communicable Diseases/parasitology ; Cytokines/immunology ; Cytokines/metabolism ; Humans ; Immunity, Innate/immunology ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/immunology ; Mesenchymal Stromal Cells/metabolism ; Toll-Like Receptors/immunology ; Toll-Like Receptors/metabolism
Chemical Substances	Cytokines ; Toll-Like Receptors
Language	English
Publishing date	2015-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	445150-8
ISSN	1879-0542 ; 0165-2478
ISSN (online)	1879-0542
ISSN	0165-2478
DOI	10.1016/j.imlet.2015.05.020
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Article ; Online: Bone marrow stromal cell-derived hepcidin has antimicrobial and immunomodulatory activities.

Krepuska, Miklós / Mayer, Balázs / Vitale-Cross, Lynn / Myneni, Vamsee D / Boyajian, Michael K / Németh, Krisztián / Szalayova, Ildikó / Cho, Ted / McClain-Caldwell, Ian / Gingerich, Aaron D / Han, Huiling / Westerman, Mark / Rada, Balázs / Mezey, Éva

Scientific reports

2024 Volume 14, Issue 1, Page(s) 3986

Abstract: Bone marrow stromal cells (BMSCs) have immunomodulatory activities in numerous species and have been used in clinical trials. BMSCs also make antibacterial agents. Since hepcidin is known to have antimicrobial effects in fish, we wondered if it might ... ...

Abstract	Bone marrow stromal cells (BMSCs) have immunomodulatory activities in numerous species and have been used in clinical trials. BMSCs also make antibacterial agents. Since hepcidin is known to have antimicrobial effects in fish, we wondered if it might also be used as an antimicrobial agent by mammalian BMSCs. In the present study, we show hepcidin expression in both mouse (mBMSC) and human BMSCs (hBMSC). We observed a hBMSC hepcidin-dependent degradation of ferroportin in HEK-293 reporter cells in vitro. In human and mouse bone marrows (BM) we detected hepcidin-positive BMSCs in close proximity to hematopoietic progenitors. The conditioned culture medium of hBMSCs significantly reduced bacterial proliferation that was partially blocked by a hepcidin-neutralizing antibody. Similarly, medium in which hepcidin-deficient (Hamp
MeSH term(s)	Humans ; Mice ; Animals ; Hepcidins/metabolism ; HEK293 Cells ; Mesenchymal Stem Cells ; Anti-Infective Agents/pharmacology ; Inflammation/metabolism ; Bone Marrow Cells ; Mammals
Chemical Substances	Hepcidins ; Anti-Infective Agents
Language	English
Publishing date	2024-02-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-54227-1
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Article ; Online: Identifying the stem cell.

Nemeth, Krisztian / Karpati, Sarolta

The Journal of investigative dermatology

2014 Volume 134, Issue 11, Page(s) 1–5

MeSH term(s)	Animals ; Bone Marrow Cells/cytology ; Cell Separation ; Cell Transdifferentiation ; Dermatology/methods ; Humans ; Membrane Potential, Mitochondrial ; Membrane Proteins/metabolism ; Mitochondria/metabolism ; Side-Population Cells/cytology ; Stem Cell Niche ; Stem Cells/cytology
Chemical Substances	Membrane Proteins
Language	English
Publishing date	2014-10-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1038/jid.2014.393
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Article ; Online: Bone marrow stromal cells as immunomodulators. A primer for dermatologists.

Nemeth, Krisztian / Mezey, Eva

Journal of dermatological science

2014 Volume 77, Issue 1, Page(s) 11–20

Abstract: Bone marrow stromal cells (BMSCs, also known as mesenchymal stem cells or MSCs) represent a unique cell population in the bone marrow with a long-known function to support hematopoiesis and replace skeletal tissues. The recent discovery that BMSCs also ... ...

Abstract	Bone marrow stromal cells (BMSCs, also known as mesenchymal stem cells or MSCs) represent a unique cell population in the bone marrow with a long-known function to support hematopoiesis and replace skeletal tissues. The recent discovery that BMSCs also possess potent immunoregulatory features attracted a great deal of attention from stem cell biologists, immunologists and clinicians of different specialties worldwide. Initial clinical experience along with several animal models suggested that intravenously delivered BMSCs are able to regulate a wide variety of host immune cells and act in a way that is beneficial for the recipient in a variety of diseases. The role of the present review is to give a short introduction to the biology of BMSCs and to summarize our current understanding of how BMSCs modulate the immune system with special emphasis on available clinical data. Considering the audience of this journal we will also attempt to guide dermatologists in choosing the right skin conditions where BMSCs might be considered as a therapeutic alternative.
MeSH term(s)	Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/immunology ; Bone Marrow Transplantation ; Dermatology/methods ; Fibrosis/immunology ; Graft vs Host Disease/immunology ; Humans ; Hypersensitivity/immunology ; Immune System/physiology ; Immunologic Factors/physiology ; Liver/immunology ; Lung/immunology ; Mice ; Skin/immunology ; Skin Diseases/therapy ; Skin Physiological Phenomena/immunology ; Stem Cells/cytology ; Stromal Cells/cytology ; Stromal Cells/immunology
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2014-10-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	1024446-3
ISSN	1873-569X ; 0923-1811
ISSN (online)	1873-569X
ISSN	0923-1811
DOI	10.1016/j.jdermsci.2014.10.004
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Zs.A 2870: Show issues

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Article ; Online: The Potential Use of THP-1, a Monocytic Leukemia Cell Line, to Predict Immune-Suppressive Potency of Human Bone-Marrow Stromal Cells (BMSCs) In Vitro: A Pilot Study.

Ren, Jiaqiang / Szombath, Gergely / Vitale-Cross, Lynn / Stroncek, David F / Robey, Pamela G / Hajdara, Anna / Szalayova, Ildiko / Mayer, Balazs / Martin, Daniel / Mezey, Eva / Nemeth, Krisztian

International journal of molecular sciences

2023 Volume 24, Issue 17

Abstract: Adoptive transfer of cultured BMSCs was shown to be immune-suppressive in various inflammatory settings. Many factors play a role in the process, but no master regulator of BMSC-driven immunomodulation was identified. Consequently, an assay that might ... ...

Abstract	Adoptive transfer of cultured BMSCs was shown to be immune-suppressive in various inflammatory settings. Many factors play a role in the process, but no master regulator of BMSC-driven immunomodulation was identified. Consequently, an assay that might predict BMSC product efficacy is still unavailable. Below, we show that BMSC donor variability can be monitored by IL-10 production of monocytes/macrophages using THP-1 cells (immortalized monocytic leukemia cells) co-cultured with BMSCs. Using a mixed lymphocyte reaction (MLR) assay, we also compared the ability of the different donor BMSCs to suppress T-cell proliferation, another measure of their immune-suppressive ability. We found that the BMSCs from a donor that induced the most IL-10 production were also the most efficient in suppressing T-cell proliferation. Transcriptome studies showed that the most potent BMSC batch also had higher expression of several known key immunomodulatory molecules such as hepatocyte growth factor (HGF), PDL1, and numerous members of the PGE2 pathway, including PTGS1 and TLR4. Multiplex ELISA experiments revealed higher expression of HGF and IL6 by the most potent BMSC donor. Based on these findings, we propose that THP-1 cells may be used to assess BMSC immunosuppressive activity as a product characterization assay.
MeSH term(s)	Humans ; Pilot Projects ; Bone Marrow ; Interleukin-10 ; Leukemia, Monocytic, Acute ; Cell Line ; Stromal Cells
Chemical Substances	Interleukin-10 (130068-27-8)
Language	English
Publishing date	2023-08-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241713258
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Article ; Online: Targeting Melanoma-Associated Fibroblasts (MAFs) with Activated γδ (Vδ2) T Cells: An In Vitro Cytotoxicity Model.

Hajdara, Anna / Çakır, Uğur / Érsek, Barbara / Silló, Pálma / Széky, Balázs / Barna, Gábor / Faqi, Shaaban / Gyöngy, Miklós / Kárpáti, Sarolta / Németh, Krisztián / Mayer, Balázs

International journal of molecular sciences

2023 Volume 24, Issue 16

Abstract: The tumor microenvironment (TME) has gained considerable scientific attention by playing a role in immunosuppression and tumorigenesis. Besides tumor cells, TME is composed of various other cell types, including cancer-associated fibroblasts (CAFs or ... ...

Abstract	The tumor microenvironment (TME) has gained considerable scientific attention by playing a role in immunosuppression and tumorigenesis. Besides tumor cells, TME is composed of various other cell types, including cancer-associated fibroblasts (CAFs or MAFs when referring to melanoma-derived CAFs) and tumor-infiltrating lymphocytes (TILs), a subpopulation of which is labeled as γδ T cells. Since the current anti-cancer therapies using γδ T cells in various cancers have exhibited mixed treatment responses, to better understand the γδ T cell biology in melanoma, our research group aimed to investigate whether activated γδ T cells are capable of killing MAFs. To answer this question, we set up an in vitro platform using freshly isolated Vδ2-type γδ T cells and cultured MAFs that were biobanked from our melanoma patients. This study proved that the addition of zoledronic acid (1-2.5 µM) to the γδ T cells was necessary to drive MAFs into apoptosis. The MAF cytotoxicity of γδ T cells was further enhanced by using the stimulatory clone 20.1 of anti-BTN3A1 antibody but was reduced when anti-TCR γδ or anti-BTN2A1 antibodies were used. Since the administration of zoledronic acid is safe and tolerable in humans, our results provide further data for future clinical studies on the treatment of melanoma.
MeSH term(s)	Humans ; Zoledronic Acid/pharmacology ; Melanoma ; Fibroblasts ; DiGeorge Syndrome ; Cancer-Associated Fibroblasts ; Tumor Microenvironment
Chemical Substances	Zoledronic Acid (6XC1PAD3KF)
Language	English
Publishing date	2023-08-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241612893
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