Stem Cell Res Ther. 2018 Oct 25;9(1):283.

Efficacy of intraoperatively prepared cell-based constructs for bone regeneration.

Zhang Y1, Grosfeld EC1, Camargo WA1, Tang H1,2, Magri AMP1,3, van den Beucken JJJP4.

Conventional cell-based bone regeneration suffers from the major disadvantage of limited cell supply, time-consuming in vitro expansion cultures, and limited patient-friendliness related to cell isolation and multiple visits to the clinic. Here, we utilized an alternative concept using "easy access cells" that can be obtained in an intraoperative manner to prepare cell-based constructs.

We used stromal vascular fraction (SVF) from human adipose tissue and human monocytes for intraoperative preparation of bone constructs. Conventional constructs grafted with expanded human adipose tissue mesenchymal stem cells (ADMSCs) derived from the same donor were set as positive controls. Additionally, we combined both cell types either or not with monocytes. The cellular interaction of human SVF and ADMSCs with human monocytes was evaluated in vitro. The feasibility and bone-regenerative capacity of intraoperative constructs were determined histologically and histomorphometrically in a rat femoral condyle bone defect model.

SVF displayed equal in vitro osteogenic differentiation compared to donor-matched expanded ADMSCs, which for both was significantly enhanced upon co-culture with monocytes. Moreover, SVF and ADMSCs displayed different immunoregulatory effects on monocytes/macrophages. Upon implantation in rat femoral bone defects, SVF constructs demonstrated superior bone formation compared to ADMSC constructs and cell-free controls; no effects of monocyte addition were observed.

In conclusion, we here demonstrate the feasibility of intraoperative SVF construct preparation and superior bone-regenerative capacity thereof compared to donor-matched ADMSC constructs. The superiority of SVF constructs was found to be linked to the distinct differences between immunoregulatory effects of SVF and ADMSCs.