{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T01:51:02Z","timestamp":1769997062269,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cystic Fibrosis Foundation"},{"name":"David and Virginia Baldwin Fund"},{"name":"Marcus Foundation"},{"name":"Case Western Reserve University Clinical and Translational Science Collaborative (CTSC)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as sustained potency through orchestrating the host immunity to optimize the resolution of infection and tissue damage. Cystic fibrosis (CF) patients suffer from a lung disease characterized by excessive inflammation and chronic infection as well as a variety of other systemic anomalies associated with the consequences of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function. The application of hMSC immunotherapy to the CF clinical armamentarium is important even in the era of modulators when patients with an established disease still need anti-inflammatory and anti-microbial therapies. Additionally, people with CF mutations not addressed by current modulator resources need anti-inflammation and anti-infection management. Furthermore, hMSCs possess dynamic therapeutic properties, but the potency of their products is highly variable with respect to their anti-inflammatory and anti-microbial effects. Due to the variability of hMSC products, we utilized standardized in vitro and in vivo models to select hMSC donor preparations with the greatest potential for clinical efficacy. The models that were used recapitulate many of the pathophysiologic outcomes associated with CF. We applied this strategy in pursuit of identifying the optimal donor to utilize for the \u201cFirst in CF\u201d Phase I clinical trial of hMSCs as an immunotherapy and anti-microbial therapy for people with cystic fibrosis. The hMSCs screened in this study demonstrated significant diversity in antimicrobial and anti-inflammatory function using models which mimic some aspects of CF infection and inflammation. However, the variability in activity between in vitro potency and in vivo effectiveness continues to be refined. Future studies require and in-depth pursuit of hMSC molecular signatures that ultimately predict the capacity of hMSCs to function in the clinical setting.<\/jats:p>","DOI":"10.3390\/ph16020220","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:06:44Z","timestamp":1675217204000},"page":"220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the \u201cFirst in Cystic Fibrosis\u201d Phase I Clinical Trial (CEASE-CF)"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9698-9113","authenticated-orcid":false,"given":"Tracey L.","family":"Bonfield","sequence":"first","affiliation":[{"name":"Department of Genetics and Genome Sciences, National Center Regenerative Medicine and Pediatrics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, BRB 822, Cleveland, OH 444106, USA"},{"name":"National Center for Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 444106, USA"},{"name":"Department of Pediatric Pulmonary, Rainbow Babies and Children\u2019s Hospital, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan T.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, National Center Regenerative Medicine and Pediatrics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, BRB 822, Cleveland, OH 444106, USA"},{"name":"National Center for Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 444106, USA"},{"name":"Department of Pediatric Pulmonary, Rainbow Babies and Children\u2019s Hospital, Cleveland, OH 44106, USA"},{"name":"Saint Jude Children\u2019s Research Hospital, Graduate School of Biomedical Sciences, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, National Center Regenerative Medicine and Pediatrics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, BRB 822, Cleveland, OH 444106, USA"},{"name":"Department of Pediatric Pulmonary, Rainbow Babies and Children\u2019s Hospital, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Reese-Koc","sequence":"additional","affiliation":[{"name":"National Center for Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 444106, USA"},{"name":"University Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica A.","family":"Roesch","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonary, Rainbow Babies and Children\u2019s Hospital, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1159-5607","authenticated-orcid":false,"given":"Hillard M.","family":"Lazarus","sequence":"additional","affiliation":[{"name":"National Center for Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 444106, USA"},{"name":"University Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James F.","family":"Chmiel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Riley Hospital for Children at IU Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold I.","family":"Caplan","sequence":"additional","affiliation":[{"name":"National Center for Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 444106, USA"},{"name":"Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1002\/ppul.24129","article-title":"Inflammation in Cystic Fibrosis: An Update","volume":"53","author":"Roesch","year":"2018","journal-title":"Pediatr Pulmonol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","article-title":"The Future of Cystic Fibrosis Care: A Global Perspective","volume":"8","author":"Bell","year":"2019","journal-title":"Lancet Respir. 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