PMID- 33003982 OWN - NLM STAT- MEDLINE DCOM- 20211015 LR - 20220802 IS - 1937-335X (Electronic) IS - 1937-3341 (Print) IS - 1937-3341 (Linking) VI - 27 IP - 15-16 DP - 2021 Aug TI - Dermal Extracellular Matrix-Derived Hydrogels as an In Vitro Substrate to Study Mast Cell Maturation. PG - 1008-1022 LID - 10.1089/ten.TEA.2020.0142 [doi] AB - Mast cells (MCs) are pro-inflammatory tissue-resident immune cells that play a key role in inflammation. MCs circulate in peripheral blood as progenitors and undergo terminal differentiation in the tissue microenvironment where they can remain for many years. This in situ maturation results in tissue- and species-specific MC phenotypes, culminating in significant variability in response to environmental stimuli. There are many challenges associated with studying mature tissue-derived MCs, particularly in humans. In cases where cultured MCs are able to differentiate in two-dimensional in vitro cultures, there remains an inability for full maturation. Extracellular matrix (ECM) scaffolds provide for a more physiologically relevant environment for cells in vitro and have been shown to modulate the response of other immune cells such as T cells, monocytes, and macrophages. To improve current in vitro testing platforms of MCs and to assess future use of ECM scaffolds for MC regulation, we studied the in vitro response of human MCs cultured on decellularized porcine dermis hydrogels (dermis extracellular matrix hydrogel [dECM-H]). This study investigated the effect of dECM-H on cellular metabolic activity, cell viability, and receptor expression compared to collagen type I hydrogel (Collagen-H). Human MCs showed different metabolic activity when cultured in the dECM-H and also upregulated immunoglobulin E (IgE) receptors associated with MC maturation/activation compared to collagen type I. These results suggest an overall benefit in the long-term culture of human MCs in the dECM-H compared to Collagen-H providing important steps toward a model that is more representative of in vivo conditions. Graphical abstract [Formula: see text] Impact statement Mast cells (MCs) are difficult to culture in vitro as current culture conditions and substrates fail to promote similar phenotypic features observed in vivo. Extracellular matrix (ECM)-based biomaterials offer three-dimensional, tissue-specific environments that more closely resemble in vivo conditions. Our study explores the use of dermal ECM hydrogels for MC culture and shows significant upregulation of metabolic activity, cell viability, and gene expression of markers associated with MC maturation or activation compared to collagen type I-hydrogel and tissue culture plastic controls at 7 days. These results are among the first to describe MC behavior in response to ECM hydrogels. FAU - Ozpinar, Emily W AU - Ozpinar EW AD - The Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Raleigh, North Carolina, USA. AD - The Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA. FAU - Frey, Ariana L AU - Frey AL AD - The Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Raleigh, North Carolina, USA. FAU - Arthur, Greer K AU - Arthur GK AD - The Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA. AD - Department of Population Heath and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA. FAU - Mora-Navarro, Camilo AU - Mora-Navarro C AD - The Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Raleigh, North Carolina, USA. AD - The Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA. FAU - Biehl, Andreea AU - Biehl A AD - The Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Raleigh, North Carolina, USA. AD - The Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA. FAU - Snider, Douglas B AU - Snider DB AD - The Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA. AD - Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA. FAU - Cruse, Glenn AU - Cruse G AD - The Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA. AD - Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA. FAU - Freytes, Donald O AU - Freytes DO AD - The Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Raleigh, North Carolina, USA. AD - The Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA. LA - eng GR - P30 ES025128/ES/NIEHS NIH HHS/United States GR - R01 AI143985/AI/NIAID NIH HHS/United States GR - T32 OD011130/OD/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20201119 PL - United States TA - Tissue Eng Part A JT - Tissue engineering. Part A JID - 101466659 RN - 0 (Hydrogels) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Cell Differentiation MH - Collagen MH - *Extracellular Matrix MH - Humans MH - Hydrogels MH - *Mast Cells MH - Swine PMC - PMC8403210 OTO - NOTNLM OT - allergy OT - extracellular matrix OT - mast cell OT - metabolism COIS- Dr. Cruse has research support from Hoth Therapeutics for a project not directly related to the research reported in this publication and also serves on their Scientific Advisory Board. The research findings included in this publication were not funded by Hoth Therapeutics and may not necessarily be related to the interests of Hoth Therapeutics. The terms of this arrangement have been reviewed and approved by NC State University in accordance with its policy on objectivity in research. The remaining authors declare no competing financial interests. EDAT- 2020/10/03 06:00 MHDA- 2021/10/16 06:00 PMCR- 2022/08/01 CRDT- 2020/10/02 05:28 PHST- 2020/10/03 06:00 [pubmed] PHST- 2021/10/16 06:00 [medline] PHST- 2020/10/02 05:28 [entrez] PHST- 2022/08/01 00:00 [pmc-release] AID - 10.1089/ten.tea.2020.0142 [pii] AID - 10.1089/ten.TEA.2020.0142 [doi] PST - ppublish SO - Tissue Eng Part A. 2021 Aug;27(15-16):1008-1022. doi: 10.1089/ten.TEA.2020.0142. Epub 2020 Nov 19.