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Book ; Online: Safety, Efficacy and Mechanisms of Action of Mesenchymal Stem Cell Therapies

Moll, Guido / Johannes Hoogduijn, Martin / Ankrum, James A.

2020

Keywords	Medicine ; Immunology ; mesenchymal stem cells ; mesenchymal stromal cells ; immunomodulation ; regeneration ; mechanism of action ; safety ; efficacy ; potency analysis
Size	1 electronic resource (296 pages)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021230001
ISBN	9782889636006 ; 2889636003
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Chemomechanically antifibrotic stromal cells.

Schrodt, Michael V / Ankrum, James A

Nature biomedical engineering

2022 Volume 6, Issue 1, Page(s) 6–7

MeSH term(s)	Fibrosis ; Humans ; Stromal Cells
Language	English
Publishing date	2022-01-21
Publishing country	England
Document type	Journal Article ; Comment
ISSN	2157-846X
ISSN (online)	2157-846X
DOI	10.1038/s41551-021-00840-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Improved MSC Minimal Criteria to Maximize Patient Safety: A Call to Embrace Tissue Factor and Hemocompatibility Assessment of MSC Products.

Moll, Guido / Ankrum, James A / Olson, Scott D / Nolta, Jan A

Stem cells translational medicine

2022 Volume 11, Issue 1, Page(s) 2–13

Abstract: The number of mesenchymal stromal/stem cell (MSC) therapeutics and types of clinical applications have greatly diversified during the past decade, including rapid growth of poorly regulated "Stem Cell Clinics" offering diverse "Unproven Stem Cell ... ...

Abstract	The number of mesenchymal stromal/stem cell (MSC) therapeutics and types of clinical applications have greatly diversified during the past decade, including rapid growth of poorly regulated "Stem Cell Clinics" offering diverse "Unproven Stem Cell Interventions." This product diversification necessitates a critical evaluation of the reliance on the 2006 MSC minimal criteria to not only define MSC identity but characterize MSC suitability for intravascular administration. While high-quality MSC therapeutics have been safely administered intravascularly in well-controlled clinical trials, repeated case reports of mild-to-more-severe adverse events have been reported. These are most commonly related to thromboembolic complications upon infusion of highly procoagulant tissue factor (TF/CD142)-expressing MSC products. As TF/CD142 expression varies widely depending on the source and manufacturing process of the MSC product, additional clinical cell product characterization and guidelines are needed to ensure the safe use of MSC products. To minimize risk to patients receiving MSC therapy, we here propose to supplement the minimal criteria used for characterization of MSCs, to include criteria that assess the suitability of MSC products for intravascular use. If cell products are intended for intravascular delivery, which is true for half of all clinical applications involving MSCs, the effects of MSC on coagulation and hemocompatibility should be assessed and expression of TF/CD142 should be included as a phenotypic safety marker. This adjunct criterion will ensure both the identity of the MSCs as well as the safety of the MSCs has been vetted prior to intravascular delivery of MSC products.
MeSH term(s)	Blood Coagulation ; Humans ; Mesenchymal Stem Cell Transplantation/adverse effects ; Mesenchymal Stem Cells/metabolism ; Thromboplastin/metabolism
Chemical Substances	Thromboplastin (9035-58-9)
Language	English
Publishing date	2022-01-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2642270-0
ISSN	2157-6580 ; 2157-6580
ISSN (online)	2157-6580
ISSN	2157-6580
DOI	10.1093/stcltm/szab005
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Article ; Online: Updating "Dataset of transcriptomic changes that occur in human preadipocytes over a 3-day course of exposure to 3,3',4,4',5-Pentachlorobiphenyl (PCB126)" with additional data on exposure to 2,2',5,5'-tetrachlorobiphenyl (PCB52) or its 4-hydroxy metabolite (4-OH-PCB52).

Gourronc, Francoise A / Chimenti, Michael S / Lehmler, Hans-Joachim / Ankrum, James A / Klingelhutz, Aloysius J

Data in brief

2023 Volume 49, Page(s) 109415

Abstract: Polychlorinated biphenyls (PCBs) were used extensively in building materials, including those used in schools. PCBs accumulate in fat, and exposure to PCBs is associated with the development of cancer, neurodevelopmental disorders, cardiovascular disease, ...

Abstract	Polychlorinated biphenyls (PCBs) were used extensively in building materials, including those used in schools. PCBs accumulate in fat, and exposure to PCBs is associated with the development of cancer, neurodevelopmental disorders, cardiovascular disease, obesity, and diabetes. The non-dioxin-like PCB congener, PCB52 (2,2',5,5'-tetrachlorobiphenyl), is found at one of the highest levels of any congener in school air. PCB52 is oxidized in the liver to hydroxylated forms, mainly 4-OH-PCB52 (2,2',5,5'-tetrachlorobiphenyl-4-ol). In a previous study, we reported on RNAseq data generated from exposure of human preadipocytes to the dioxin-like PCB congener, PCB126. In this new dataset, we used identical techniques to examine alterations in gene transcript levels in human preadipocytes exposed to PCB52 or 4-OH-PCB52 over a time course. This updated set of data provides a comprehensive transcriptional profile of changes that occur in preadipocytes exposed to PCB52 or 4-OH-PCB52 over time and allows for comparison of these changes between the parent compound and its hydroxy metabolite. The datasets will allow others to explore how PCB52 and 4-OH-PCB52 impact biological pathways in preadipocytes. Further studies can be performed to determine how these changes might lead to disease.
Language	English
Publishing date	2023-07-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2786545-9
ISSN	2352-3409 ; 2352-3409
ISSN (online)	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2023.109415
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Article ; Online: The Impact of High Adiposity on Endometrial Progesterone Response and Metallothionein Regulation.

Murphy, Alina R / Asif, Huma / Cingoz, Harun / Gourronc, Françoise A / Ankrum, James A / Klingelhutz, Aloysius J / Kim, J Julie

The Journal of clinical endocrinology and metabolism

2024

Abstract: Context: Obesity is a disease with deleterious effects on the female reproductive tract, including the endometrium.: Objective: We sought to understand the effects of excess adipose on the benign endometrium.: Design: A physiologic in vitro ... ...

Abstract	Context: Obesity is a disease with deleterious effects on the female reproductive tract, including the endometrium. Objective: We sought to understand the effects of excess adipose on the benign endometrium. Design: A physiologic in vitro coculture system was developed, consisting of multicellular human endometrial organoids, adipose spheroids, and menstrual cycle hormones. Native human endometrial tissue samples women with and without obesity were also analyzed. Setting: Academic institution. Patients: Benign endometrial tissues from premenopausal women were obtained following written consent. Main outcome measures: Gene expression, protein expression, chromatin binding, and expression of DNA damage and oxidative damage markers were measured. Results: Under high-adiposity conditions, endometrial organoids downregulated endometrial secretory phase genes, suggestive of an altered progesterone response. Progesterone specifically upregulated the metallothionein (MT) gene family in the epithelial cells of endometrial organoids, while high adiposity significantly downregulated the MT genes. Silencing MT genes in endometrial epithelial cells resulted in increased DNA damage, illustrating the protective role of MTs. Native endometrium from women with obesity displayed increased MT expression and oxidative damage in the stroma and not in the epithelium, indicating the cell-specific impact of obesity on MT genes. Conclusions: Taken together, the in vitro and in vivo systems used here revealed that high adiposity or obesity can alter MT expression by decreasing progesterone response in the epithelial cells and increasing oxidative stress in the stroma.
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgae236
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Article ; Online: Hydroxylation markedly alters how the polychlorinated biphenyl (PCB) congener, PCB52, affects gene expression in human preadipocytes.

Gourronc, Francoise A / Chimenti, Michael S / Lehmler, Hans-Joachim / Ankrum, James A / Klingelhutz, Aloysius J

Toxicology in vitro : an international journal published in association with BIBRA

2023 Volume 89, Page(s) 105568

Abstract: Polychlorinated biphenyls (PCBs) accumulate in adipose tissue and are linked to obesity and diabetes. The congener, PCB52 (2,2',5,5'-tetrachorobiphenyl), is found at high levels in school air. Hydroxylation of PCB52 to 4-OH-PCB52 (4-hydroxy-2,2',5,5'- ... ...

Abstract	Polychlorinated biphenyls (PCBs) accumulate in adipose tissue and are linked to obesity and diabetes. The congener, PCB52 (2,2',5,5'-tetrachorobiphenyl), is found at high levels in school air. Hydroxylation of PCB52 to 4-OH-PCB52 (4-hydroxy-2,2',5,5'-tetrachorobiphenyl) may increase its toxicity. To understand PCB52's role in causing adipose dysfunction, we exposed human preadipocytes to PCB52 or 4-OH-PCB52 across a time course and assessed transcript changes using RNAseq. 4-OH-PCB52 caused considerably more changes in the number of differentially expressed genes as compared to PCB52. Both PCB52 and 4-OH-PCB52 upregulated transcript levels of the sulfotransferase SULT1E1 at early time points, but cytochrome P450 genes were generally not affected. A set of genes known to be transcriptionally regulated by PPARα were consistently downregulated by PCB52 at all time points. In contrast, 4-OH-PCB52 affected a variety of pathways, including those involving cytokine responses, hormone responses, focal adhesion, Hippo, and Wnt signaling. Sets of genes known to be transcriptionally regulated by IL17A or parathyroid hormone (PTH) were found to be consistently downregulated by 4-OH-PCB52. Most of the genes affected by PCB52 and 4-OH-PCB52 were different and, of those that were the same, many were changed in an opposite direction. These studies provide insight into how PCB52 or its metabolites may cause adipose dysfunction to cause disease.
MeSH term(s)	Humans ; Polychlorinated Biphenyls/toxicity ; Hydroxylation ; Cytochrome P-450 Enzyme System/metabolism ; Gene Expression
Chemical Substances	Polychlorinated Biphenyls (DFC2HB4I0K) ; Cytochrome P-450 Enzyme System (9035-51-2)
Language	English
Publishing date	2023-02-15
Publishing country	England
Document type	Journal Article
ZDB-ID	639064-x
ISSN	1879-3177 ; 0887-2333
ISSN (online)	1879-3177
ISSN	0887-2333
DOI	10.1016/j.tiv.2023.105568
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Article ; Online: Editorial: Safety, Efficacy and Mechanisms of Action of Mesenchymal Stem Cell Therapies.

Moll, Guido / Hoogduijn, Martin J / Ankrum, James A

Frontiers in immunology

2020 Volume 11, Page(s) 243

MeSH term(s)	Apoptosis ; Freezing ; Humans ; Mesenchymal Stem Cell Transplantation/adverse effects ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/physiology ; Signal Transduction/physiology
Language	English
Publishing date	2020-02-18
Publishing country	Switzerland
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00243
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Article ; Online: Translating MSC Therapy in the Age of Obesity.

Boland, Lauren / Bitterlich, Laura Melanie / Hogan, Andrew E / Ankrum, James A / English, Karen

Frontiers in immunology

2022 Volume 13, Page(s) 943333

Abstract: Mesenchymal stromal cell (MSC) therapy has seen increased attention as a possible option to treat a number of inflammatory conditions including COVID-19 acute respiratory distress syndrome (ARDS). As rates of obesity and metabolic disease continue to ... ...

Abstract	Mesenchymal stromal cell (MSC) therapy has seen increased attention as a possible option to treat a number of inflammatory conditions including COVID-19 acute respiratory distress syndrome (ARDS). As rates of obesity and metabolic disease continue to rise worldwide, increasing proportions of patients treated with MSC therapy will be living with obesity. The obese environment poses critical challenges for immunomodulatory therapies that should be accounted for during development and testing of MSCs. In this review, we look to cancer immunotherapy as a model for the challenges MSCs may face in obese environments. We then outline current evidence that obesity alters MSC immunomodulatory function, drastically modifies the host immune system, and therefore reshapes interactions between MSCs and immune cells. Finally, we argue that obese environments may alter essential features of allogeneic MSCs and offer potential strategies for licensing of MSCs to enhance their efficacy in the obese microenvironment. Our aim is to combine insights from basic research in MSC biology and clinical trials to inform new strategies to ensure MSC therapy is effective for a broad range of patients.
MeSH term(s)	COVID-19/therapy ; Cells, Cultured ; Humans ; Immunomodulation ; Mesenchymal Stem Cells/metabolism ; Obesity/metabolism ; Obesity/therapy
Language	English
Publishing date	2022-07-04
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.943333
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Article ; Online: Native adiponectin plays a role in the adipocyte-mediated conversion of fibroblasts to myofibroblasts.

El-Hattab, Mariam Y / Sinclair, Noah / Liszewski, Jesse N / Schrodt, Michael V / Herrmann, Jacob / Klingelhutz, Aloysius J / Sander, Edward A / Ankrum, James A

Journal of the Royal Society, Interface

2023 Volume 20, Issue 202, Page(s) 20230004

Abstract: Adipocytes regulate tissues through production of adipokines that can act both locally and systemically. Adipocytes also have been found to play a critical role in regulating the healing process. To better understand this role, we developed a three- ... ...

Abstract	Adipocytes regulate tissues through production of adipokines that can act both locally and systemically. Adipocytes also have been found to play a critical role in regulating the healing process. To better understand this role, we developed a three-dimensional human adipocyte spheroid system that has an adipokine profile similar to
MeSH term(s)	Humans ; Myofibroblasts/metabolism ; Transforming Growth Factor beta1/pharmacology ; Transforming Growth Factor beta1/metabolism ; Adiponectin/metabolism ; Signal Transduction/physiology ; Fibroblasts/metabolism ; Adipocytes/metabolism ; Lipids ; Actins/metabolism ; Cell Differentiation ; Cells, Cultured
Chemical Substances	Transforming Growth Factor beta1 ; Adiponectin ; Lipids ; Actins
Language	English
Publishing date	2023-05-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2156283-0
ISSN	1742-5662 ; 1742-5689
ISSN (online)	1742-5662
ISSN	1742-5689
DOI	10.1098/rsif.2023.0004
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl.

Behan-Bush, Riley M / Liszewski, Jesse N / Schrodt, Michael V / Vats, Bhavya / Li, Xueshu / Lehmler, Hans-Joachim / Klingelhutz, Aloysius J / Ankrum, James A

Environmental science & technology

2023 Volume 57, Issue 4, Page(s) 1731–1742

Abstract: Polychlorinated biphenyl (PCB) accumulates in adipose where it may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein, we sought to understand how exposure ... ...

Abstract	Polychlorinated biphenyl (PCB) accumulates in adipose where it may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein, we sought to understand how exposure to PCB mixtures found in U.S. schools affects human adipose mesenchymal stem/stromal cell (MSC) health and function. We investigated how exposure to Aroclor 1016 and Aroclor 1254, as well as a newly characterized non-Aroclor mixture that resembles the PCB profile found in cabinets, Cabinet Mixture, affects adipose MSC growth, viability, and function in vitro. We found that exposure to all three mixtures resulted in two distinct types of toxicity. At PCB concentrations >20 μM, the majority of MSCs die, while at 1-10 μM, MSCs remained viable but display numerous alterations to their phenotype. At these sublethal concentrations, the MSC rate of expansion slowed and morphology changed. Further assessment revealed that PCB-exposed MSCs had impaired adipogenesis and a modest decrease in immunosuppressive capabilities. Thus, exposure to PCB mixtures found in schools negatively impacts the health and function of adipose MSCs. This work has implications for human health due to MSCs' role in supporting the growth and maintenance of adipose tissue.
MeSH term(s)	Humans ; Polychlorinated Biphenyls/toxicity ; Polychlorinated Biphenyls/metabolism ; Aroclors/metabolism ; Aroclors/toxicity ; Chlorodiphenyl (54% Chlorine)/metabolism ; Adipose Tissue ; Stromal Cells/metabolism
Chemical Substances	Polychlorinated Biphenyls (DFC2HB4I0K) ; Aroclors ; Chlorodiphenyl (54% Chlorine) (11097-69-1)
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.2c07281
Database	MEDical Literature Analysis and Retrieval System OnLINE

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