{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:41:54Z","timestamp":1760060514499,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"NEI","doi-asserted-by":"publisher","award":["R01EY012601","R01EY028858","R01EY028037","R01EY025383","R01EY033620","R01EY032753","P30 EY003039"],"award-info":[{"award-number":["R01EY012601","R01EY028858","R01EY028037","R01EY025383","R01EY033620","R01EY032753","P30 EY003039"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH Core Grant for Vision Research","award":["R01EY012601","R01EY028858","R01EY028037","R01EY025383","R01EY033620","R01EY032753","P30 EY003039"],"award-info":[{"award-number":["R01EY012601","R01EY028858","R01EY028037","R01EY025383","R01EY033620","R01EY032753","P30 EY003039"]}]},{"name":"Research to Prevent Blindness Unrestricted Grant","award":["R01EY012601","R01EY028858","R01EY028037","R01EY025383","R01EY033620","R01EY032753","P30 EY003039"],"award-info":[{"award-number":["R01EY012601","R01EY028858","R01EY028037","R01EY025383","R01EY033620","R01EY032753","P30 EY003039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Purpose: We previously reported that the systemic administration of preprogrammed mouse hematopoietic bone marrow-derived progenitor cells (HSPCs) improved visual function and restored a functional retinal pigment epithelial (RPE) layer. Here, we investigated the potential impact of donor vs. host age on systemic cellular therapy in a murine model of retinal degeneration. Methods: HSPCs from young (8 weeks) and old (15 months) mice were programmed ex vivo with a lentiviral vector expressing the RPE65 gene (LV-RPE65) and systemically administering into young or old SOD2 KD mice. Visual loss and pathological changes were evaluated by electroretinogram (ERG), optical coherence tomography (OCT), histology, and immunohistochemistry. Results: Old donor HSPCs administered to old manganese superoxide dismutase (SOD2) knockdown (KD) recipient mice offered the least benefit. This was exemplified by the reduced recruitment and incorporation of LV-RPE65 HSPC into the RPE layer, as well as decreased improvement in visual function, retinal thinning, and limited reduction in oxidative damage and microglial activation. LV-RPE65 HSPC from young mice incorporated into the RPE layer of old SOD2 KD mice, though to a lesser extent than young cells administered to young hosts, offered some level of protection. By contrast, LV-RPE65 HSPCs from old mice, located to the subretinal space of young host mice, reduced visual loss, although some retinal pathology was observed. Conclusions: The administration of LV-RPE65 HSPC from old donors to old SOD2 KD mice offered the least improvement. Translational Relevance: Our findings highlight how both donor and recipient age impact the success of HSPC-based retinal therapy and using cells from aged donors for AMD treatment may have some limitations.<\/jats:p>","DOI":"10.3390\/cells14171360","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T08:28:15Z","timestamp":1756715295000},"page":"1360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Donor and Host Age on Systemic Cell Therapy to Treat Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-3124","authenticated-orcid":false,"given":"Carolina","family":"Francelin","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6768-405X","authenticated-orcid":false,"given":"Xiaoping","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1276-4297","authenticated-orcid":false,"given":"Juliana","family":"Godoy","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Hospital Israelita Albert Einstein, Sao Paulo 04829-310, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2101-2543","authenticated-orcid":false,"given":"Brenton T.","family":"Bicknell","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1931-5040","authenticated-orcid":false,"given":"Ram","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria B.","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0796-1766","authenticated-orcid":false,"given":"Michael E.","family":"Boulton","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1089\/hgtb.2017.082","article-title":"Improving the Transduction of Bone Marrow-Derived Cells with an Integrase-Defective Lentiviral Vector","volume":"29","author":"Pay","year":"2018","journal-title":"Hum. 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