{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T06:00:18Z","timestamp":1762063218914,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T00:00:00Z","timestamp":1660262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish research council","doi-asserted-by":"publisher","award":["2020-02014","20200917","2019-00846"],"award-info":[{"award-number":["2020-02014","20200917","2019-00846"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009673","name":"Hj\u00e4rnfonden, Demensfonden, Lindh\u00e9s stiftelse, Gun and Bertil Stohne\u2019s Foundation","doi-asserted-by":"publisher","award":["2020-02014","20200917","2019-00846"],"award-info":[{"award-number":["2020-02014","20200917","2019-00846"]}],"id":[{"id":"10.13039\/100009673","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gamla Tj\u00e4narinnor stiftelse","award":["2020-02014","20200917","2019-00846"],"award-info":[{"award-number":["2020-02014","20200917","2019-00846"]}]},{"name":"\u00c5hlen stiftelse, Alzheimerfonden, Tore Nilsson stiftelse, KI Geriatric research","award":["2020-02014","20200917","2019-00846"],"award-info":[{"award-number":["2020-02014","20200917","2019-00846"]}]},{"name":"ALF Foundation for medicine","award":["2020-02014","20200917","2019-00846"],"award-info":[{"award-number":["2020-02014","20200917","2019-00846"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There is no cure yet available for Alzheimer\u2019s disease (AD). We recently optimized encapsulated cell biodelivery (ECB) devices releasing human mature nerve growth factor (hmNGF), termed ECB-NGF, to the basal forebrain of AD patients. The ECB-NGF delivery resulted in increased CSF cholinergic markers, improved glucose metabolism, and positive effects on cognition in AD patients. However, some ECB-NGF implants showed altered hmNGF release post-explantation. To optimize the ECB-NGF platform for future therapeutic purposes, we initiated in-vitro optimization studies by exposing ECB-NGF devices to physiological factors present within the AD brain. We report here that microglia cells can impair hmNGF release from ECB-NGF devices in-vitro, which can be reversed by transferring the devices to fresh culture medium. Further, we exposed the hmNGF secreting human ARPE-19 cell line (NGC0211) to microglia (HMC3) conditioned medium (MCM; untreated or treated with IL-1\u03b2\/IFN\u03b3\/A\u03b240\/A\u03b242), and evaluated biochemical stress markers (ROS, GSH, \u0394\u03a8m, and Alamar Blue assay), cell death indicators (Annexin-V\/PI), cell proliferation (CFSE retention and Ki67) and senescence markers (SA-\u03b2-gal) in NGC0211 cells. MCMs from activated microglia reduced cell proliferation and induced cell senescence in NGC0211 cells, which otherwise resist biochemical alterations and cell death. These data indicate a critical but reversible impact of activated microglia on NGC0211 cells.<\/jats:p>","DOI":"10.3390\/ijms23169011","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T01:47:21Z","timestamp":1660528041000},"page":"9011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Microglia Impairs Proliferation and Induces Senescence In-Vitro in NGF Releasing Cells Used in Encapsulated Cell Biodelivery for Alzheimer\u2019s Disease Therapy"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6381-5344","authenticated-orcid":false,"given":"Sumonto","family":"Mitra","sequence":"first","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of NVS, Karolinska Institutet, 141 52 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruchi","family":"Gera","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of NVS, Karolinska Institutet, 141 52 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Sundheimer","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of NVS, Karolinska Institutet, 141 52 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marine","family":"Lemee","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of NVS, Karolinska Institutet, 141 52 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars U.","family":"Wahlberg","sequence":"additional","affiliation":[{"name":"Gloriana Therapeutics, Inc., Providence, RI 02885, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bengt","family":"Linderoth","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Eriksdotter","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of NVS, Karolinska Institutet, 141 52 Huddinge, Sweden"},{"name":"Theme Inflammation and Aging, Karolinska University Hospital, 141 86 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Homira","family":"Behbahani","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of NVS, Karolinska Institutet, 141 52 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6023","DOI":"10.1038\/s41380-020-0797-2","article-title":"The human brain NGF metabolic pathway is impaired in the pre-clinical and clinical continuum of Alzheimers disease","volume":"26","author":"Pentz","year":"2021","journal-title":"Mol. 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