{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:04:59Z","timestamp":1779311099221,"version":"3.51.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Research Foundation of Korea (NRF) funded by the Ministry of Education"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Neural regeneration remains a critical goal in regenerative medicine, especially for treating central nervous system injuries such as stroke, spinal cord injury, and neurodegenerative diseases. Mesenchymal stem cells (MSCs) have shown therapeutic potential through their capacity for differentiation and paracrine signaling; however, their clinical application is limited by low survival and engraftment rates. In this study, we investigated whether the therapeutic efficacy of human MSC (hMSC) spheroids could be enhanced through photobiomodulation (PBM). hMSCs were aggregated into three-dimensional spheroids and divided into four experimental groups: (1) untreated control spheroids, (2) spheroids treated with 660\u202fnm PBM, (3) spheroids treated with 850\u202fnm PBM, and (4) spheroids co-cultured with primary rat cortical neurons subjected to oxidative stress using hydrogen peroxide (H\u2082O\u2082). The PBM groups were exposed to red (660\u202fnm) or near-infrared (NIR; 850\u202fnm) light for 10\u202fmin. Neuronal viability and axonal regeneration were assessed. Our results demonstrated that PBM-treated hMSC spheroids significantly increased neuronal survival and axonal outgrowth compared to H\u2082O\u2082-only controls, particularly under high oxidative stress conditions. Notably, spheroids treated with 850\u202fnm PBM exhibited the most robust neuroprotective effects. These findings suggest that PBM enhances mitochondrial activity and the secretion of neurotrophic factors by hMSC spheroids, thereby promoting neuroregeneration. This combinatorial strategy integrating PBM with 3D stem cell spheroid culture offers a promising avenue for developing advanced stem cell therapies for neurological disorders.<\/jats:p>","DOI":"10.3389\/fncel.2026.1728579","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T05:22:25Z","timestamp":1769664145000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Photobiomodulation (PBM) irradiation enhances the therapeutic potential of hMSC spheroids for neural repair"],"prefix":"10.3389","volume":"20","author":[{"given":"So-Young","family":"Chang","sequence":"first","affiliation":[{"name":"Beckman Laser Institute Korea, Dankook University","place":["Cheonan, Republic of Korea"]},{"name":"Medical Laser Research Center, College of Medicine, Dankook University","place":["Cheonan, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namgue","family":"Hong","sequence":"additional","affiliation":[{"name":"Medical Laser Research Center, College of Medicine, Dankook University","place":["Cheonan, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Eun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head & Neck Surgery, College of Medicine, Dankook University","place":["Cheonan, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Chul","family":"Ahn","sequence":"additional","affiliation":[{"name":"Beckman Laser Institute Korea, Dankook University","place":["Cheonan, Republic of Korea"]},{"name":"Medical Laser Research Center, College of Medicine, Dankook University","place":["Cheonan, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Beckman Laser Institute Korea, Dankook University","place":["Cheonan, Republic of Korea"]},{"name":"Medical Laser Research Center, College of Medicine, Dankook University","place":["Cheonan, Republic of Korea"]},{"name":"Department of Otolaryngology-Head & Neck Surgery, College of Medicine, Dankook University","place":["Cheonan, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/s12951-025-03298-x","article-title":"Development of NIR photocleavable nanoparticles with BDNF for vestibular neuron regeneration","volume":"23","author":"Abueva","year":"2025","journal-title":"J Nanobiotechnol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2002944","DOI":"10.1002\/advs.202002944","article-title":"Mesenchymal stem cells for neurological disorders","volume":"8","author":"Andrzejewska","year":"2021","journal-title":"Adv Sci (Weinh)"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.7874\/jao.2023.00164","article-title":"Can Cochlear nerve size assessment with magnetic resonance enhance the understanding of idiopathic sudden sensorineural hearing loss?","volume":"28","author":"Arslan","year":"2024","journal-title":"J Audiol Otol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"5543","DOI":"10.7150\/thno.107345","article-title":"Shh agonist enhances maturation in homotypic Lgr5-positive inner ear organoids","volume":"15","author":"Carpena","year":"2025","journal-title":"Theranostics"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.actbio.2019.09.022","article-title":"Characterizing the impact of 2D and 3D culture conditions on the therapeutic effects of human mesenchymal stem cell secretome on corneal wound healing in vitro and ex vivo","volume":"99","author":"Carter","year":"2019","journal-title":"Acta Biomater."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.omtm.2020.03.010","article-title":"Enhanced inner-ear organoid formation from mouse embryonic stem cells by Photobiomodulation","volume":"17","author":"Chang","year":"2020","journal-title":"Mol Ther Methods Clin Dev"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"6845571","DOI":"10.1155\/2023\/6845571","article-title":"Photobiomodulation can enhance stem cell viability in cochlea with auditory neuropathy but does not restore hearing","volume":"2023","author":"Chang","year":"2023","journal-title":"Stem Cells Int."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1007\/s10103-021-03268-3","article-title":"Photobiomodulation with a wavelength > 800 nm induces morphological changes in stem cells within otic organoids and scala media of the cochlea","volume":"36","author":"Chang","year":"2021","journal-title":"Lasers Med. 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