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Although synthetic bone substitutes or osteogenesis-inducing recombinant proteins were introduced to promote bone union, the rate of revision surgery is still high due to pseudarthrosis. To promote successful fusion after surgery, stem cells with or without biomaterials were introduced; however, conventional 2D-culture environments have resulted in a considerable loss of the innate therapeutic properties of stem cells. Therefore, we conducted a preclinical study applying 3D-spheroids of human bone marrow-dewrived mesenchymal stem cells (MSCs) to a mouse spinal fusion model. First, we built a large-scale manufacturing platform for MSC spheroids, which is applicable to good manufacturing practice (GMP). Comprehensive biomolecular examinations, which include liquid chromatography-mass spectrometry and bioinformatics could suggest a framework of quality control (QC) standards for the MSC spheroid product regarding the identity, purity, viability, and potency. In our animal study, the mass-produced and quality-controlled MSC spheroids, either undifferentiated or osteogenically differentiated were well-integrated into decorticated bone of the lumbar spine, and efficiently improved angiogenesis, bone regeneration, and mechanical stability with statistical significance compared to 2D-cultured MSCs. This study proposes a GMP-applicable bioprocessing platform and QC directions of MSC spheroids aiming for their clinical application in spinal fusion surgery as a new bone graft substitute.<\/jats:p>","DOI":"10.1093\/stcltm\/szac052","type":"journal-article","created":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:09:00Z","timestamp":1664582940000},"page":"1072-1088","source":"Crossref","is-referenced-by-count":12,"title":["Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion"],"prefix":"10.1093","volume":"11","author":[{"given":"Sumin","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Mechatronics Engineering, College of Engineering, Incheon National University , Incheon , Republic of Korea"},{"name":"3D Stem Cell Bioengineering Laboratory, Research Institute for Engineering and Technology, Incheon National University , Incheon , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-236X","authenticated-orcid":false,"given":"Hyemin","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center , Seongnam-si, Gyeonggi-do , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyundoo","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Mechatronics Engineering, College of Engineering, Incheon National University , Incheon , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Yeon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center , Seongnam-si, Gyeonggi-do , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6337-9754","authenticated-orcid":false,"given":"Eun Ji","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center , Seongnam-si, Gyeonggi-do , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Hun","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Mechatronics Engineering, College of Engineering, Incheon National University , Incheon , Republic of Korea"},{"name":"3D Stem Cell Bioengineering Laboratory, Research Institute for Engineering and Technology, Incheon National University , Incheon , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inho","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Biomedical Technology, Dongguk University , Goyang-si, Gyeonggi-do , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Technology, Dongguk University , Goyang-si, Gyeonggi-do , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Hong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Technology, Dongguk University , Goyang-si, Gyeonggi-do , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-9325","authenticated-orcid":false,"given":"Inbo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center , Seongnam-si, Gyeonggi-do , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Min","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of 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