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Center for Advancing Translational Sciences"},{"name":"U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences"},{"name":"U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences"},{"name":"U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Microgravity"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Determining the physiological effects of microgravity on the human kidney is limited to relatively insensitive tests of biofluids (blood and urine) that do not return abnormal results until more than 50% of kidney function is lost. We have developed an \u201corgan on chip\u201d microphysiological model of the human kidney proximal tubule (PT-MPS) that can recapitulate many kidney functions and disease states and could play a critical role in determining mechanisms of early kidney dysfunction in microgravity. However, the ground-based PT-MPS system is incompatible with spaceflight as it requires a large pneumatic system coupled to a cell incubator for perfusion and intensive hand-on manipulation. Herein, we report the hardware engineering and performance of the Kidney Chip Perfusion Platform (KCPP), a small, advanced, semi-autonomous hardware platform to support kidney microphysiological model experiments in microgravity. The KCPP is composed of five components, the kidney MPS, the MPS housing and valve block, media cassettes, fixative cassettes, and the programable precision syringe pump. The system has been deployed twice to the ISSNL (aboard CRS-17 and CRS-22). From each set of ISSNL experiments and ground-based controls, we were able to recover PT-MPS effluent for biomarker analysis and RNA suitable for transcriptomics analysis demonstrating the usability and functionality of the KCPP.<\/jats:p>","DOI":"10.1038\/s41526-024-00398-0","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T04:01:54Z","timestamp":1715400114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Development of a kidney microphysiological system hardware platform for microgravity studies"],"prefix":"10.1038","volume":"10","author":[{"given":"Kendan A.","family":"Jones-Isaac","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"Lidberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-6641","authenticated-orcid":false,"given":"Catherine K.","family":"Yeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3195-218X","authenticated-orcid":false,"given":"Jade","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacelyn","family":"Bain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3707-5589","authenticated-orcid":false,"given":"Micaela","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Koenig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Koenig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Countryman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Himmelfarb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-9313","authenticated-orcid":false,"given":"Edward J.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,11]]},"reference":[{"key":"398_CR1","doi-asserted-by":"publisher","first-page":"C567","DOI":"10.1152\/ajpcell.00203.2021","volume":"322","author":"PHU Lee","year":"2022","unstructured":"Lee, P. H. U., Chung, M., Ren, Z., Mair, D. B. & Kim, D. H. Factors mediating spaceflight-induced skeletal muscle atrophy. Am. J. Physiol. Cell Physiol. 322, C567\u2013C580 (2022).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"398_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/s41526-022-00194-8","volume":"8","author":"J Man","year":"2022","unstructured":"Man, J., Graham, T., Squires-Donelly, G. & Laslett, A. L. The effects of microgravity on bone structure and function. NPJ Microgravity 8, 9 (2022).","journal-title":"NPJ Microgravity"},{"key":"398_CR3","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1159\/000252852","volume":"56","author":"J Vernikos","year":"2010","unstructured":"Vernikos, J. & Schneider, V. S. Space, gravity and the physiology of aging: parallel or convergent disciplines? A mini-review. Gerontology 56, 157\u2013166 (2010).","journal-title":"Gerontology"},{"key":"398_CR4","doi-asserted-by":"publisher","unstructured":"Mao, X. W. et al. Impact of spaceflight and artificial gravity on the mouse retina: biochemical and proteomic analysis. Int. J. Mol. Sci. 19, https:\/\/doi.org\/10.3390\/ijms19092546 (2018).","DOI":"10.3390\/ijms19092546"},{"key":"398_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49453-x","volume":"9","author":"EG Overbey","year":"2019","unstructured":"Overbey, E. G. et al. Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina. Sci. Rep. 9, 13304 (2019).","journal-title":"Sci. Rep."},{"key":"398_CR6","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.2215\/CJN.09750913","volume":"10","author":"J Blaine","year":"2015","unstructured":"Blaine, J., Chonchol, M. & Levi, M. Renal control of calcium, phosphate, and magnesium homeostasis. Clin. J. Am. Soc. Nephrol. 10, 1257\u20131272 (2015).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"398_CR7","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1177\/15353702221091982","volume":"247","author":"K Young","year":"2022","unstructured":"Young, K., Beggs, M. R., Grimbly, C. & Alexander, R. T. Regulation of 1 and 24 hydroxylation of vitamin D metabolites in the proximal tubule. Exp. Biol. Med. 247, 1103\u20131111 (2022).","journal-title":"Exp. Biol. Med."},{"key":"398_CR8","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.2215\/CJN.14890920","volume":"15","author":"A Koirala","year":"2020","unstructured":"Koirala, A. & Jefferson, J. A. How safe is a native kidney biopsy? Clin. J. Am. Soc. Nephrol. 15, 1541\u20131542 (2020).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"398_CR9","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.kint.2016.06.011","volume":"90","author":"EJ Weber","year":"2016","unstructured":"Weber, E. J. et al. Development of a microphysiological model of human kidney proximal tubule function. Kidney Int. 90, 627\u2013637 (2016).","journal-title":"Kidney Int."},{"key":"398_CR10","doi-asserted-by":"publisher","unstructured":"Chang, S. Y. et al. Human liver-kidney model elucidates the mechanisms of aristolochic acid nephrotoxicity. JCI Insight 2, https:\/\/doi.org\/10.1172\/jci.insight.95978 (2017).","DOI":"10.1172\/jci.insight.95978"},{"key":"398_CR11","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1681\/ASN.2021060751","volume":"33","author":"KA Lidberg","year":"2022","unstructured":"Lidberg, K. A. et al. Serum protein exposure activates a core regulatory program driving human proximal tubule injury. J. Am. Soc. Nephrol. 33, 949\u2013965 (2022).","journal-title":"J. Am. Soc. Nephrol."},{"key":"398_CR12","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1681\/ASN.2015010060","volume":"27","author":"M Adler","year":"2016","unstructured":"Adler, M. et al. A quantitative approach to screen for nephrotoxic compounds in vitro. J. Am. Soc. Nephrol. 27, 1015\u20131028 (2016).","journal-title":"J. Am. Soc. Nephrol."},{"key":"398_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84194-w","volume":"11","author":"KA Lidberg","year":"2021","unstructured":"Lidberg, K. A. et al. Antisense oligonucleotide development for the selective modulation of CYP3A5 in renal disease. Sci. Rep. 11, 4722 (2021).","journal-title":"Sci. Rep."},{"key":"398_CR14","doi-asserted-by":"publisher","unstructured":"Weber, E. J. et al. Human kidney on a chip assessment of polymyxin antibiotic nephrotoxicity. JCI Insight 3, https:\/\/doi.org\/10.1172\/jci.insight.123673 (2018).","DOI":"10.1172\/jci.insight.123673"},{"key":"398_CR15","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1002\/psp4.12400","volume":"8","author":"C Maass","year":"2019","unstructured":"Maass, C. et al. Translational assessment of drug-induced proximal tubule injury using a kidney microphysiological system. CPT Pharmacomet. Syst. Pharm. 8, 316\u2013325 (2019).","journal-title":"CPT Pharmacomet. Syst. Pharm."},{"key":"398_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33099-2","volume":"8","author":"C Sakolish","year":"2018","unstructured":"Sakolish, C. et al. Technology transfer of the microphysiological systems: a case study of the human proximal tubule tissue chip. Sci. Rep. 8, 14882 (2018).","journal-title":"Sci. Rep."},{"key":"398_CR17","doi-asserted-by":"publisher","first-page":"504","DOI":"10.14573\/altex.1803161","volume":"35","author":"BD Chapron","year":"2018","unstructured":"Chapron, B. D. et al. Reevaluating the role of megalin in renal vitamin D homeostasis using a human cell-derived microphysiological system. Altex 35, 504\u2013515 (2018).","journal-title":"Altex"},{"key":"398_CR18","doi-asserted-by":"publisher","unstructured":"Lidberg, K. et al. Impact of microgravity on a three-dimensional microphysiologic culture of the human kidney proximal tubule epithelium: cell response to serum and vitamin D. Preprint at Research Square, https:\/\/doi.org\/10.21203\/rs.3.rs-3778779\/v1 (2023).","DOI":"10.21203\/rs.3.rs-3778779\/v1"},{"key":"398_CR19","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/toxsci\/kfs268","volume":"131","author":"VS Sabbisetti","year":"2013","unstructured":"Sabbisetti, V. S. et al. Novel assays for detection of urinary KIM-1 in mouse models of kidney injury. Toxicol. Sci. 131, 13\u201325 (2013).","journal-title":"Toxicol. Sci."},{"key":"398_CR20","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41536-021-00156-w","volume":"6","author":"A Schumacher","year":"2021","unstructured":"Schumacher, A. et al. Defining the variety of cell types in developing and adult human kidneys by single-cell RNA sequencing. NPJ Regen. Med. 6, 45 (2021).","journal-title":"NPJ Regen. 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