Efficacy of intraoperatively prepared cell-based constructs for bone regeneration

Abstract

BackgroundConventional 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.MethodsWe 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.ResultsSVF 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.ConclusionIn 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.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1026-7) contains supplementary material, which is available to authorized users.

Cryopreserved human adipose-derived stromal vascular fraction maintains fracture healing potential via angiogenesis and osteogenesis in an immunodeficient rat model

“…Although a study conducted on the ADSC stored for longer than 10 years has reported that long-term cryopreservation maintains cell viability with certain negative effects on osteogenic potential of ADSCs [61], for better clarity on SVF, comparison between different cryopreservation periods using the same animal model is ideal and should be considered. Several recent studies have reported the therapeutic potential of cryopreserved SVF has for bone healing in equine fracture [33] and rat bone defect models [34]. However, to the best of our knowledge, our study is the first to compare the therapeutic benefits of fracture healing using the same animal unhealing fracture model between freshly isolated and cryopreserved SVFs, and strengthen the evidence of usefulness of cryopreservation of SVFs to efficiently maintain angiogenic and osteogenic potentials.…”

“…Cryopreservation is an appropriate solution since SVF cells can be easily frozen and stored, while maintaining the proliferative capacity and differentiation potential [31]. Recent studies have demonstrated the therapeutic potential of rat SVF for bone fracture in 8 human patients [32]; while cryopreserved SVF cells have been shown to facilitate bone healing in an equine carpal chip fracture [33] and rat bone defect model [34]. However, no study has compared the therapeutic benefits of fracture healing using the same animal model between freshly isolated and cryopreserved SVFs.…”

Secreted Factors and EV-miRNAs Orchestrate the Healing Capacity of Adipose Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis

“…In this frame, in previous reports, bone marrow MSCs promoted changes in the M1/M2 balance in vitro [99]. This paradigm may also explain the in vitro observation that both ASCs and SVF induced macrophage polarization toward a pro-wound healing M2 type [100]. Therefore, thanks to secreted factors, ASCs in enriched tissues as MFAT or SVF can attenuate M1 macrophages by shifting them to an M2 state, laying the foundations for injury resolution in inflammatory-stimulating environments, such as OA joints.…”

Bone tumor–targeted delivery of theranostic 195mPt-bisphosphonate complexes promotes killing of metastatic tumor cells

“…After fixation, tibia samples from each group were decalcified in an EDTA (ethylenediaminetetraacetic acid) solution, dehydrated in a series of alcohol, and embedded in paraffin, as reported previously [ 24 ]. The specimens were sectioned at a thickness of 5 ​μm using a standard microtome (RM 2165; Leica).…”