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

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 diabe...

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Autores principales:	Rebecca P. Chow, Kevin Nguyen, Wenyu Gou, Erica Green, Katherine Morgan, William Lancaster, Kristi Helke, Charlie Strange, Hongjun Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mesenchymal stromal cells chronic pancreatitis pain inflammation TRPV1 mast cells Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/199fa17d916b41bb8947c4af6bc5e38c
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spelling	oai:doaj.org-article:199fa17d916b41bb8947c4af6bc5e38c2021-11-25T16:50:55ZA Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells10.3390/biomedicines91116952227-9059https://doaj.org/article/199fa17d916b41bb8947c4af6bc5e38c2021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1695https://doaj.org/toc/2227-9059Chronic 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 × 10<sup>6</sup> cells/mouse, i.v., <i>n</i> = 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.Rebecca P. ChowKevin NguyenWenyu GouErica GreenKatherine MorganWilliam LancasterKristi HelkeCharlie StrangeHongjun WangMDPI AGarticlemesenchymal stromal cellschronic pancreatitispaininflammationTRPV1mast cellsBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1695, p 1695 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mesenchymal stromal cells chronic pancreatitis pain inflammation TRPV1 mast cells Biology (General) QH301-705.5
spellingShingle	mesenchymal stromal cells chronic pancreatitis pain inflammation TRPV1 mast cells Biology (General) QH301-705.5 Rebecca P. Chow Kevin Nguyen Wenyu Gou Erica Green Katherine Morgan William Lancaster Kristi Helke Charlie Strange Hongjun Wang A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells
description	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 × 10<sup>6</sup> cells/mouse, i.v., <i>n</i> = 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.
format	article
author	Rebecca P. Chow Kevin Nguyen Wenyu Gou Erica Green Katherine Morgan William Lancaster Kristi Helke Charlie Strange Hongjun Wang
author_facet	Rebecca P. Chow Kevin Nguyen Wenyu Gou Erica Green Katherine Morgan William Lancaster Kristi Helke Charlie Strange Hongjun Wang
author_sort	Rebecca P. Chow
title	A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells
title_short	A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells
title_full	A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells
title_fullStr	A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells
title_full_unstemmed	A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells
title_sort	novel cellular therapy to treat pancreatic pain in experimental chronic pancreatitis using human alpha-1 antitrypsin overexpressing mesenchymal stromal cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/199fa17d916b41bb8947c4af6bc5e38c
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A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells

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