Immunological influence of serum-free manufactured umbilical cord-derived mesenchymal stromal cells for steroid-resistant acute graft-versus-host disease.
Tokiko Nagamura-InoueSeiko KatoYuho NajimaMasamichi IsobeNoriko DokiHisashi YamamotoNaoyuki UchidaAtsuko TakahashiAkiko HoriMasanori NojimaKazuteru OhashiFumitaka NagamuraArinobu TojoPublished in: International journal of hematology (2022)
This study investigated the safety, efficacy, and immunological influence of allogeneic umbilical cord-derived mesenchymal stromal cells (IMSUT-CORD) processed in serum-free medium and cryoprotectant, for treating steroid-resistant acute graft-versus-host disease (aGVHD). In a phase I dose-escalation trial, IMSUT-CORD were infused intravenously twice weekly over two cycles with up to two additional cycles. Four patients received a dose of 1 × 10 6 cells/kg, while three received 2 × 10 6 /kg. Of 76 total adverse events, fourteen associated or possibly associated adverse events included 2 cases of a hot flash, headache, and peripheral neuropathy, 1 each of upper abdominal pain, hypoxia, increased γ-GTP, somnolence, peripheral vascular pain at the injection site, thrombocytopenia, hypertension, and decreased fibrinogen. At 16 weeks after the initial IMSUT-CORD infusion, three patients showed complete response (CR), two partial response (PR), one mixed response, and one no response. The overall response rate was 71.4%, and the continuous CR/PR rate was 100% for over 28 days after CR/PR. NK cell count significantly increased and correlated with treatment response, whereas IL-12, IL-17, and IL-33 levels decreased, but did not correlate with treatment response. CCL2 and CCL11 levels increased during IMSUT-CORD therapy. IMSUT-CORD are usable in patients with steroid-resistant aGVHD (UMIN000032819: https://www.umin.ac.jp/ctr ).
Keyphrases
- umbilical cord
- mesenchymal stem cells
- end stage renal disease
- bone marrow
- ejection fraction
- newly diagnosed
- chronic kidney disease
- peritoneal dialysis
- induced apoptosis
- liver failure
- blood pressure
- chronic pain
- stem cells
- stem cell transplantation
- cell proliferation
- endothelial cells
- oxidative stress
- spinal cord
- liver fibrosis
- respiratory failure
- cell death
- high resolution
- cell cycle arrest
- ultrasound guided
- nk cells
- pi k akt