Bone regeneration in critical-size calvarial defects using human dental pulp cells in an extracellular matrix-based scaffold.

The rat calvarial defect is an established model to evaluate craniofacial bone regeneration using cell-scaffold biocomplexes. Dental pulp harbors stem cells with significant osteogenic properties. Extracellular matrix (ECM)-like scaffolds simulate the environment that cells observe in vivo. In the present study, we evaluated the osteogenic effect of a biocomplex of human dental pulp cells and a hyaluronic-based hydrogel scaffold in calvarial defects of immunocompetent rats. Dental pulp cells at the 2nd passage were characterized by flow cytometry, osteodifferentiated ex vivo for 4 days and the whole population was encapsulated in the synthetic ECM matrix. Cell vitality was verified 24 h upon encapsulation. 5 mm calvarial defects were created in 30 male rats and filled with the biocomplex, the scaffold alone, or left untreated. Histological evaluation at 8 weeks showed incomplete bone regeneration in all groups. The scaffold was not fully degraded and entrapped cells were detected in it. Histomorphometry showed statistically significant superior new bone formation in the biocomplex-treated group, compared to the two other groups. The present study provides evidence that the whole population of human dental pulp cells can advance bone healing when transplanted in immunocompetent animals and highlights the importance of proper scaffold degradation in cell-driven bioengineering treatments.

Humoral immune reactivity against human leukocyte antigen (HLA)-DQ graft molecules in the early posttransplantation period.

Humoral graft-specific alloreactivity was investigated in 110 renal transplant (RTx) recipients (group A) starting immediately postTx and in 32 RTx candidates sensitized against a failed graft (group B) using an enzyme-linked immunosorbent assay (ELISA) assay. All patients received a human leukocyte antigen (HLA) class I and II incompatible graft. Donor-specific (DS) antibodies were detected in 11 of 110 (90.9%) group-A patients, predominately during the first 6 months postTx. In all 11 cases, only HLA class II antibodies were detected. Ten of 11 antibody-positive patients received an HLA-DR, HLA-DQ incompatible graft, and all patients had HLA-DQ DS antibodies, either alone (n=8) or with HLA-DR antibodies (n=2). HLA-DQ antibodies were also detected in 80.9% of group-B patients. The presence of HLA-DQ DS antibodies in the early postTx period does not identify patients with rejection or deterioration of graft function. Whether these patients are at high risk for graft loss remains to be clarified.