Osteoarthritis and cartilage open · 2026
Preclinical and early clinical safety of intra-articular spheroid adipose-derived stem cells for knee osteoarthritis: A translational study.
СтатьяНазвание и аннотация: Перевод в очереди
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Sobajima Satoshi, Harada Yusuke, Kim Tae-Sun, Kisaki Osamu, Otera Kaito, Yamauchi Hitoshi, Umemoto Hiroshi, Makino Tomomi, Nagao Emiko, Iwaguro Hideki
Аннотация
OBJECTIVE: To evaluate preclinical and early clinical safety of intra-articular spheroid adipose-derived stem cells (S-ADSCs) for knee osteoarthritis and to summarize exploratory outcomes.
METHODS: This program included a minipig study (n = 3; Day 31) and a clinical cohort (n = 5; Week 52). Each knee received 42,000 spheroids (500 cells/spheroid; 2.1 × 107 cells) in 5 mL. Preclinical assessments included clinical monitoring, laboratory tests, necropsy, and H&E histology of distal femur, proximal tibia, and medial/lateral menisci. In patients, adverse events and serious adverse events were captured through Week 52; exploratory outcomes included pain (visual analog scale [VAS]) and function (KOOS and WOMAC). Exploratory quadratic mixed-effects models assessed non-linear time trends.
RESULTS: Minipigs showed no abnormal clinical signs, laboratory changes, or treatment-related findings at necropsy or on knee histology through Day 31. All five patients completed 52-week follow-up; no treatment-related adverse events or serious adverse events, infections, hemarthroses, or acute post-injection flares requiring medical treatment occurred. Exploratory outcomes were heterogeneous: two participants showed sustained improvement through Week 52, whereas the remaining three showed non-sustained patterns; two improved early with partial return toward baseline, and one experienced transient pain worsening at Week 4 without objective inflammation or infection followed by later recovery. Quadratic models suggested early improvement with later attenuation.
CONCLUSION: Intra-articular S-ADSC spheroids at this dose demonstrated acceptable safety in a large-animal model and a first-in-human cohort, supporting further controlled studies.
TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTb050200097; first public release December 17, 2020).
METHODS: This program included a minipig study (n = 3; Day 31) and a clinical cohort (n = 5; Week 52). Each knee received 42,000 spheroids (500 cells/spheroid; 2.1 × 107 cells) in 5 mL. Preclinical assessments included clinical monitoring, laboratory tests, necropsy, and H&E histology of distal femur, proximal tibia, and medial/lateral menisci. In patients, adverse events and serious adverse events were captured through Week 52; exploratory outcomes included pain (visual analog scale [VAS]) and function (KOOS and WOMAC). Exploratory quadratic mixed-effects models assessed non-linear time trends.
RESULTS: Minipigs showed no abnormal clinical signs, laboratory changes, or treatment-related findings at necropsy or on knee histology through Day 31. All five patients completed 52-week follow-up; no treatment-related adverse events or serious adverse events, infections, hemarthroses, or acute post-injection flares requiring medical treatment occurred. Exploratory outcomes were heterogeneous: two participants showed sustained improvement through Week 52, whereas the remaining three showed non-sustained patterns; two improved early with partial return toward baseline, and one experienced transient pain worsening at Week 4 without objective inflammation or infection followed by later recovery. Quadratic models suggested early improvement with later attenuation.
CONCLUSION: Intra-articular S-ADSC spheroids at this dose demonstrated acceptable safety in a large-animal model and a first-in-human cohort, supporting further controlled studies.
TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTb050200097; first public release December 17, 2020).