Off-label mesenchymal stromal cell treatment in two infants with severe bronchopulmonary dysplasia: clinical course and biomarkers profile.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most prevalent sequelae of premature birth, for which therapeutic options are currently limited. Mesenchymal stromal cells (MSCs) are a potential therapy for prevention or reversal of BPD. SERIES OF CASES: We report on two infants with severe BPD in whom off-label treatment with repeated intravenous doses of allogeneic bone marrow-derived MSCs were administered. We analyzed the temporal profile of serum and tracheal cytokines and growth factors as well as safety, tolerability and clinical response. The administration of repeated intravenous doses of MSCs in two human babies with severe and advanced BPD was feasible and safe and was associated with a decrease of pro-inflammatory molecules and lung injury biomarkers. Both patients were at very advanced stages of BPD with very severe lung fibrosis and did not survive the disease. CONCLUSIONS: MSCs are a promising therapy for BPD, but they should be administered in early stages of the disease.

Nuclear factor-kappaB inducing kinase is required for graft-versus-host disease.

BACKGROUND: Donor T lymphocytes are directly responsible for graft-versus-host disease. Molecules important in T-cell function may, therefore, be appropriate targets for graft-versus-host disease therapy and/or prophylaxis. Here we analyzed whether nuclear factor-κ B inducing kinase might have a role in graft-versus-host disease. DESIGN AND METHODS: We studied the expression of nuclear factor-κ B inducing kinase in human samples from patients with graft-versus-host disease. We also explored the effect of nuclear factor-κ B inducing kinase in a murine model of graft-versus-host disease using donor cells from aly/aly mice (deficient in nuclear factor-κ B inducing kinase) and C57BL/6 mice (control). RESULTS: We detected expression of nuclear factor-κ B inducing kinase in T-lymphocytes in the pathological lesions of patients with acute graft-versus-host disease. Mice transplanted with aly/aly T lymphocytes did not develop graft-versus-host disease at all, while mice receiving C57BL/6 cells died of a lethal form of the disease. Deficiency of nuclear factor-κ B inducing kinase did not affect the engrafting ability of donor T cells, but severely impaired their expansion capacity early after transplantation, and aly/aly T cells showed a higher proportion of apoptosis than did C57BL/6 T cells. Effector T lymphocytes were the T-cell subset most affected by nuclear factor-κ B inducing kinase deficiency. We also detected lower amounts of inflammatory cytokines in the serum of mice receiving aly/aly T cells than in the serum of mice receiving C57BL/6 T cells. CONCLUSIONS: Our results show that nuclear factor-κ B inducing kinase has a role in graft-versus-host disease by maintaining the viability of activated alloreactive T lymphocytes.

Paciente con hepatitis autoinmunitaria y púrpura trombocitopénicaidiopática tras un tratamiento con minociclina / Treatment of painful splenomegaly by partial splenic embolization

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