24 research outputs found
Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial
Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS. A double-blind, phase 1/2a, randomized, controlled trial was performed. Randomization and stratification by ARDS severity was used to foster balance among groups. All subjects were analyzed under intention to treat design. Twenty-four subjects were randomized 1:1 to either UC-MSC treatment (n = 12) or the control group (n = 12). Subjects in the UC-MSC treatment group received two intravenous infusions (at day 0 and 3) of 100 ± 20 × 106 UC-MSCs; controls received two infusions of vehicle solution. Both groups received best standard of care. Primary endpoint was safety (adverse events [AEs]) within 6 hours; cardiac arrest or death within 24 hours postinfusion). Secondary endpoints included patient survival at 31 days after the first infusion and time to recovery. No difference was observed between groups in infusion-associated AEs. No serious adverse events (SAEs) were observed related to UC-MSC infusions. UC-MSC infusions in COVID-19 ARDS were found to be safe. Inflammatory cytokines were significantly decreased in UC-MSC-treated subjects at day 6. Treatment was associated with significantly improved patient survival (91% vs 42%, P =.015), SAE-free survival (P =.008), and time to recovery (P =.03). UC-MSC infusions are safe and could be beneficial in treating subjects with COVID-19 ARDS
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The effect of simultaneous CD154 and LFA-1 blockade on the survival of allogeneic islet grafts in nonobese diabetic mice
The rate of success in clinical transplantation of islets of Langerhans has dramatically improved with perspectives of wide-scale applicability for patients with type 1 diabetes. One drawback is the need for lifelong immunosuppression, which is associated with significant side effects. Immunomodulatory strategies devoid of side effects and with tolerogenic potential, such as co-stimulatory blockade, would be a great improvement if successful. In this study, the authors have explored the effect of simultaneous blockade of CD40/CD154 and intercellular adhesion molecule (ICAM)/lymphocyte function-associated antigen (LFA)-1 interactions
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Improved human islet isolation outcome from marginal donors following addition of oxygenated perfluorocarbon to the cold-storage solution
HLA-B Matching Prolongs Allograft Survival in Islet Cell Transplantation
Islet cell transplantation (ITx) is an effective therapeutic approach for selected patients with type 1 diabetes with hypoglycemia unawareness and severe hypoglycemia events. In organ transplantation, human leukocyte antigen (HLA) mismatching between donor and recipient negatively impacts transplant outcomes. We aimed to determine whether HLA matching has an impact on islet allograft survival. Forty-eight patients were followed up after islet transplantation at our institution from 2000 to 2020 in a retrospective cohort. Patients underwent intrahepatic ITx or laparoscopic omental approach. Immunosuppression was dependent upon the protocol. We analyzed HLA data restricted to A, B, and DR loci on allograft survival using survival and subsequent multivariable analyses. Patients were aged 42.8 ± 8.4 years, and 64.3% were female. Diabetes duration was 28.6 ± 11.6 years. Patients matching all three HLA loci presented longer graft survival ( P = 0.030). Patients with ≥1 HLA-B matching had longer graft survival compared with zero matching ( P = 0.025). The number of HLA-B matching was positively associated with time of graft survival (Spearman’s rho = 0.590; P = 0.034). Analyses adjusted for confounders showed that ≥1 matching for HLA-B decreased the risk of allograft failure ( P = 0.009). Our data suggest that HLA-B matching between recipients and donors improved islet allograft survival. Matching all three HLA loci (A, B, and DR) was also associated with prolonged islet allograft survival. Prospective studies and a larger sample size are warranted to validate our findings
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P.106: Prolonged Islet Allograft Function in Patients With Type 1 Diabetes After Islet Transplantation Is Associated With Female Sex of Donors and Recipients
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Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and anti-interleukin-2 antibody
Nonobese diabetic (NOD) mice develop autoimmune diabetes with features similar to those observed in the human disease. The concurrence of allorecognition and recurrence of autoimmunity might explain why most of the treatments successful in preventing islet allograft destruction in other nonautoimmune combinations often fail in NOD recipients. To assess the value of the NOD mouse model for the evaluation of treatments relevant to clinical islet transplantation, the authors have tested the effect of a protocol closely resembling the one successfully used in the Edmonton clinical trial on the survival of islet allografts in NOD mice
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Prolonged allogeneic islet graft survival by protoporphyrins
Transplantation of islets of Langerhans in patients with type 1 diabetes allows for improved metabolic control and insulin independence. The need for chronic immunosuppression limits this procedure to selected patients with brittle diabetes. Definition of therapeutic strategies allowing permanent engraftment without the need for chronic immunosuppression could overcome such limitations. We tested the effect of the use of protoporphyrins (CoPP and FePP), powerful inducers of the cytoprotective protein heme-oxygenase 1 (HO-1), on allogeneic islet graft survival. Chemically induced diabetic C57BL/6 mice received DBA/2 islets. Treatment consisted in peritransplant administration of CoPP or saline. Islets were either cultured in the presence of FePP or vehicle before implant. Short-course administration of CoPP led to long-term islet allograft survival in a sizable proportion of recipients. Long-term graft-bearing animals rejected third-party islets while accepting a second set donor-specific graft permanently, without additional treatment. Preconditioning of islets with FePP by itself led to improved graft survival in untreated recipients, and provided additional advantage in CoPP-treated recipients, resulting in an increased proportion of long-term surviving grafts. Preconditioning of the graft with protoporphyrins prior to implant resulted in reduction of class II expression. Administration of protoporphyrins to the recipients of allogeneic islets also resulted in transient powerful immunosuppression with reduced lymphocyte proliferative responses, increased proportion of regulatory cells (CD4+CD25+), decreased mononuclear cell infiltrating the graft, paralleled by a systemic upregulation of HO-1 expression. All these mechanisms may have contributed to the induction of donor-specific hyporesponsiveness in a proportion of the protoporphyrin-treated animals