Relative contributions of adipose-resident CD146⁺ pericytes and CD34⁺ adventitial progenitor cells in bone tissue engineering

Pericytes and other perivascular stem/stromal cells are of growing interest in the field of tissue engineering. A portion of perivascular cells are well recognized to have MSC (mesenchymal stem cell) characteristics, including multipotentiality, self-renewal, immunoregulatory functions, and diverse roles in tissue repair. Here, we investigate the differential but overlapping roles of two perivascular cell subsets in paracrine induction of bone repair. CD146⁺CD34⁻CD31⁻CD45⁻pericytes and CD34⁺CD146⁻CD31⁻CD45⁻adventitial cells were derived from human adipose tissue and applied alone or in combination to calvarial bone defects in mice. In vitro, osteogenic differentiation and tubulogenesis assays were performed using either fluorescence activated cell sorting-derived CD146⁺ pericytes or CD34⁺ adventitial cells. Results showed that CD146⁺ pericytes induced increased cord formation in vitro and angiogenesis in vivo in comparison with patient-matched CD34⁺ adventitial cells. In contrast, CD34⁺ adventitial cells demonstrated heightened paracrine-induced osteogenesis in vitro. When applied in a critical-size calvarial defect model in NOD/SCID mice, the combination treatment of CD146⁺ pericytes with CD34⁺ adventitial cells led to greater re-ossification than either cell type alone. In summary, adipose-derived CD146⁺ pericytes and CD34⁺ adventitial cells display functionally distinct yet overlapping and complementary roles in bone defect repair. Consequently, CD146⁺ pericytes and CD34⁺ adventitial cells may demonstrate synergistic bone healing when applied as a combination cellular therapy.