{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:50:47Z","timestamp":1791935447984,"version":"4.3.4"},"reference-count":63,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Hope Biosciences, LLC"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM008792"],"award-info":[{"award-number":["T32GM008792"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clare A. Glassell Family Pediatric Surgery Research Endowment"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Secondary injury from traumatic brain injury (TBI) leads to chronic inflammatory processes, neurodegeneration and tissue loss, resulting in poor outcomes. Mesenchymal stromal cell (MSC) treatment can dampen microglial activation and improve TBI outcomes. Our study aimed to assess the impact of autologous adipose-derived MSC treatment in adult patients with chronic TBI using imaging, functional and neurocognitive outcome measures.<\/jats:p>\n                  <jats:p>Our phase 1\/2a study analysed the safety and treatment effect of three intravenous infusions (over 6 weeks) of autologous adipose-derived MSCs (HB-adMSCs) in 24 patients with chronic TBI. Outcome measures included functional, neuropsychological and psychometric testing, multimodal MRI, and PET using 11C-ER176 to measure brain immune cell density. There were no serious treatment-related adverse events. Diffusion tensor MRI analyses in a priori regions of interest showed that at 6 months after treatment, elevated mean diffusivity volumes (supraMD) were significantly reduced bilaterally in the hippocampus (mean decrease 163.51\u2005mm3, 95% confidence interval \u2212286.55 to \u221241.51\u2005mm3; P = 0.013). A trend for reduced supraMD was observed in the amygdala (mean decrease 113.60\u2005mm3, 95% confidence interval \u2212229.52\u20132.90\u2005mm3; P = 0.058); no changes in the insula were observed (P = 0.19). Brain-behaviour analyses indicated significant interactions between levels in baseline neuropsychological assessments of anxiety and depression and magnitude of supraMD changes in the amygdala and hippocampus, respectively. Macrostructural volumetric changes were not significant in the hippocampus, amygdala or insula (all P \u2265 0.10).<\/jats:p>\n                  <jats:p>PET results showed that HB-adMSC treatment induced significant reductions in brain immune cell density in the right caudate [x, y, z: 12, 2, 7; T(20) = 4.1; P &amp;lt; 0.0003], extending into both the right ventral anterior thalamus [x, y, z: 13, \u22122, 11; T(20) = 3.6; P &amp;lt; 0.0009] and right nucleus accumbens [x, y, z: 8, 9, \u22123; T(20) = 2.5; P &amp;lt; 0.01], and right parahippocampal gyrus [x, y, z: 29, \u221240, \u22127; T(20) = 3.1; P &amp;lt; 0.003]. Reductions in measures of depression (P = 0.026), fatigue (P = 0.008) and pain (P = 0.007) 6 months after treatment were also observed.<\/jats:p>\n                  <jats:p>Our study demonstrates autologous adipose-derived MSCs for chronic TBI are safe, have clinically relevant treatment effect sizes in functional and neurocognitive outcome measures, yield significant improvements in specified measures of microstructural integrity [i.e. reduced volume of elevated mean diffusivity (MD) voxels] in brain-based behaviour relations and reduce density of brain immune cells in regions corresponding to pain, fatigue and depression. These data provide quantitative justification for the sample size of next-phase clinical trials using either functional outcomes or surrogate imaging outcomes.<\/jats:p>","DOI":"10.1093\/brain\/awag165","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:39:26Z","timestamp":1778067566000},"source":"Crossref","is-referenced-by-count":1,"title":["Autologous adipose-derived mesenchymal stromal cells for chronic traumatic brain injury"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9155-3676","authenticated-orcid":false,"suffix":"Jr","given":"Charles S","family":"Cox","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]},{"name":"Program in Regenerative Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]},{"name":"Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet R","family":"Ashley","sequence":"additional","affiliation":[{"name":"Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenifer","family":"Juranek","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]},{"name":"Program in Regenerative Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Ewing-Cobbs","sequence":"additional","affiliation":[{"name":"The Institute for Clinical Research and Learning Health Care, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]},{"name":"Children's Learning Institute, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R","family":"Prossin","sequence":"additional","affiliation":[{"name":"Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]},{"name":"Neuroimmune Brain Assay Research Program, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Pedroza","sequence":"additional","affiliation":[{"name":"The Institute for Clinical Research and Learning Health Care, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingrui","family":"Chen","sequence":"additional","affiliation":[{"name":"The Institute for Clinical Research and Learning Health Care, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Kosmach","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmen","family":"Duron","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]},{"name":"Program in Regenerative Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidan","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 ,","place":["USA"]},{"name":"Program in Regenerative Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston) , Houston, TX 77030 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