scholarly journals P.150: Alpha-1 Antitrypsin Engineered Mesenchymal Stromal Cells Improves Human Islet Survival via Regulation of Macrophage Activation

2021 ◽  
Vol 105 (12S1) ◽  
pp. S62-S62
Author(s):  
Hongjun Wang
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Macrophage Activation ◽  
Human Islet ◽  
Alpha 1 Antitrypsin ◽  
Islet Survival

Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model

Diabetologia ◽  
2013 ◽  
Vol 57 (3) ◽  
pp. 522-531 ◽  
Author(s):  
Danielle J. Borg ◽  
Marc Weigelt ◽  
Carmen Wilhelm ◽  
Michael Gerlach ◽  
Marc Bickle ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Islet Function ◽  
Syngeneic Mouse ◽  
Syngeneic Mouse Model ◽  
Islet Survival

scholarly journals A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1695
Author(s):  
Rebecca P. Chow ◽  
Kevin Nguyen ◽  
Wenyu Gou ◽  
Erica Green ◽  
Katherine Morgan ◽  
...  
Keyword(s):  
Mast Cell ◽  
Abdominal Pain ◽  
Chronic Pancreatitis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Transient Receptor Potential Vanilloid ◽  
Trinitrobenzene Sulfonic Acid ◽  
Human Mscs ◽  
Pancreatic Morphology ◽  
Alpha 1 Antitrypsin

Chronic pancreatitis (CP) is characterized by pancreatic inflammation, fibrosis, and abdominal pain that is challenging to treat. Mesenchymal stromal cells (MSCs) overexpressing human alpha-1 antitrypsin (hAAT-MSCs) showed improved mobility and protective functions over native MSCs in nonobese diabetic mice. We investigated whether hAAT-MSCs could mitigate CP and its associated pain using trinitrobenzene sulfonic acid (TNBS)-induced CP mouse models. CP mice were given native human MSCs or hAAT-MSCs (0.5 × 106 cells/mouse, i.v., n = 6–8/group). The index of visceral pain was measured by graduated von Frey filaments. Pancreatic morphology and pancreatic mast cell count were analyzed by morphological stains. Nociceptor transient receptor potential vanilloid 1 (TRPV1) expression in dorsal root ganglia (DRG) was determined by immunohistochemistry. hAAT-MSC-treated CP mice best preserved pancreatic morphology and histology. MSC or hAAT-MSC infusion reduced abdominal pain sensitivities. hAAT-MSC therapy also suppressed TRPV1 expression in DRG and reduced pancreatic mast cell density induced by TNBS. Overall, hAAT-MSCs reduced pain and mitigated pancreatic inflammation in CP equal to MSCs with a trend toward a higher pancreatic weight and better pain relief in the hAAT-MSC group compared to the MSC group. Both MSCs and hAAT-MSCs might be used as a novel therapeutic tool for CP-related pain.

scholarly journals Proteomic Analysis of Exosomes Secreted from Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells

Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 9
Author(s):  
Hua Wei ◽  
Erica Green ◽  
Lauren Ball ◽  
Hongkuan Fan ◽  
Jennifer Lee ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Proteomic Analysis ◽  
Donor Cell ◽  
Stem Cell Differentiation ◽  
Cytokine Signaling ◽  
Therapeutic Effects ◽  
Associated Proteins ◽  
Control Mscs ◽  
Alpha 1 Antitrypsin

Extracellular vesicles (EVs) mediate many therapeutic effects of stem cells during cellular therapies. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) were manufactured to overexpress the human antiprotease alpha-1 antitrypsin (hAAT) and studied to compare the EV production compared to lentivirus treated control MSCs. The goal of this study was to compare protein profiles in the EVs/exosomes of control and hAAT-MSCs using unbiased, high resolution liquid chromatography and mass spectrometry to explore differences. Nanoparticle tracking analysis (NTA) showed that the particle size of the EVs from control MSCs or hAAT-MSCs ranged from 30 to 200 nm. Both MSCs and hAAT-MSCs expressed exosome-associated proteins, including CD63, CD81, and CD9. hAAT-MSCs also expressed high levels of hAAT. We next performed proteomic analysis of EVs from three healthy donor cell lines. Exosomes collected from cell supernatant were classified by GO analysis which showed proteins important to cell adhesion and extracellular matrix organization. However, there were differences between exosomes from control MSCs and hAAT-MSCs in cytokine signaling of the immune system, stem cell differentiation, and carbohydrate metabolism (p < 0.05). These results show that hAAT-MSC exosomes contain a different profile of paracrine effectors with altered immune function, impacts on MSC stemness, differentiation, and prevention of cell apoptosis and survival that could contribute to improved therapeutic functions.

scholarly journals Alpha-1 Antitrypsin-Expressing Mesenchymal Stromal Cells Confer a Long-Term Survival Benefit in a Mouse Model of Lethal GvHD

2019 ◽  
Vol 27 (8) ◽  
pp. 1436-1451
Author(s):  
Sabine Geiger ◽  
Emrah I. Ozay ◽  
Ulf Geumann ◽  
Marina K. Hereth ◽  
Terese Magnusson ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Survival Benefit ◽  
Term Survival ◽  
Long Term Survival ◽  
Alpha 1 Antitrypsin

Human Islet-Derived Precursor Cells Are Mesenchymal Stromal Cells That Differentiate and Mature to Hormone-Expressing Cells In Vivo

Stem Cells ◽  
2007 ◽  
Vol 25 (12) ◽  
pp. 3215-3222 ◽  
Author(s):  
Behrous Davani ◽  
Laertis Ikonomou ◽  
Bruce M. Raaka ◽  
Elizabeth Geras-Raaka ◽  
Russell A. Morton ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Precursor Cells ◽  
Human Islet

Erratum to: Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model

Diabetologia ◽  
2014 ◽  
Vol 57 (5) ◽  
pp. 1086-1086
Author(s):  
Danielle J. Borg ◽  
Marc Weigelt ◽  
Carmen Wilhelm ◽  
Michael Gerlach ◽  
Marc Bickle ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Islet Function ◽  
Syngeneic Mouse ◽  
Syngeneic Mouse Model ◽  
Islet Survival

scholarly journals Characterization of the Effects of Mesenchymal Stromal Cells on Mouse and Human Islet Function

2019 ◽  
Author(s):  
Ahmed A. Arzouni ◽  
Andreia Vargas‐Seymour ◽  
Paramjeet K. Dhadda ◽  
Chloe L. Rackham ◽  
Guo‐Cai Huang ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Islet ◽  
Islet Function

Bone marrow-derived mesenchymal stromal cells support rat pancreatic islet survival and insulin secretory function in vitro

Cytotherapy ◽  
2011 ◽  
Vol 13 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Eun-Jung Jung ◽  
Song-Cheol Kim ◽  
Yu-Mee Wee ◽  
Yang-Hee Kim ◽  
Monica Young Choi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pancreatic Islet ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Secretory Function ◽  
Islet Survival ◽  
Rat Pancreatic Islet

scholarly journals Mesenchymal stromal cells improve human islet function through released products and extracellular matrix

2017 ◽  
Vol 131 (23) ◽  
pp. 2835-2845 ◽  
Author(s):  
Ahmed A. Arzouni ◽  
Andreia Vargas-Seymour ◽  
Chloe L. Rackham ◽  
Paramjeet Dhadda ◽  
Guo-Cai Huang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Islets ◽  
Human Islet ◽  
Human Mscs ◽  
Islet Function ◽  
Secretory Function ◽  
Beneficial Effects

Aims: The aims of the present study were (i) to determine whether the reported beneficial effects of mesenchymal stromal cells (MSCs) on mouse islet function extend to clinically relevant human tissues (islets and MSCs), enabling translation into improved protocols for clinical human islet transplantation; and (ii) to identify possible mechanisms through which human MSCs influence human islet function. Materials and methods: Human islets were co-cultured with human adipose tissue-derived MSCs (hASCs) or pre-treated with its products – extracellular matrix (ECM) and annexin A1 (ANXA1). Mouse islets were pre-treated with mouse MSC-derived ECM. Islet insulin secretory function was assessed in vitro by radioimmunoassay. Quantitative RT-PCR was used to screen human adipMSCs for potential ligands of human islet G-protein-coupled receptors. Results: We show that co-culture with hASCs improves human islet secretory function in vitro, as measured by glucose-stimulated insulin secretion, confirming previous reports using rodent tissues. Furthermore, we demonstrate that these beneficial effects on islet function can be partly attributed to the MSC-derived products ECM and ANXA1. Conclusions: Our results suggest that hASCs have the potential to improve the quality of human islets isolated for transplantation therapy of Type 1 diabetes. Furthermore, it may be possible to achieve improvements in human islet quality in a cell-free culture system by using the MSC-derived products ANXA1 and ECM.

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