Abstract
Stromal vascular fraction (SVF), an adipose tissue-derived heterogeneous cell mixture containing, among others, multipotent adipose stromal cells (ASCs) and erythrocytes, has proved beneficial for a wide range of applications in regenerative medicine. We sought to establish intervertebral disc(IVD) regeneration by injecting SVF intradiscally during a one-step surgical procedure in an enzymatically (Chondroitinase ABC; cABC) induced goat model of disc degeneration. Unexpectedly, we observed a severe inflammatory response that has not been described before, including massive lymphocyte infiltration, neovascularisation and endplate destruction. A second study investigated two main suspects for these adverse effects: cABC and erythrocytes within SVF. The same destructive response was observed in healthy goat discs injected with SVF, thereby eliminating cABC as a cause. Density gradient removal of erythrocytes and ASCs purified by culturing did not lead to adverse effects. Following these observations, we incorporated an extra washing step in the SVF harvesting protocol. In a third study, we applied this protocol in a one-step procedure to a goat herniation model, in which no adverse responses were observed either. However, upon intradiscal injection of an identically processed SVF mixture into our goat IVD degeneration model during a fourth study, the adverse effects surprisingly occurred again. Despite our quest for the responsible agent, we eventually could not identify the mechanism through which the observed destructive responses occurred. Although we cannot exclude that the adverse effects are species-dependent or model-specific, we advertise caution with the clinical application of autologous SVF injections into the IVD until the responsible agent(s) are identified.
Highlights
A comprehensive number of diseases and degenerative conditions have recently been treated successfully with stromal vascular fraction (SVF), a mixture of various cell types derived from adipose tissue
This paper primarily describes our consistent observations of a severe inflammatory response to autologous SVF injections in goat discs after prior enzymatically induced degeneration
We showed that the adverse events were not caused by CABC, because the response occurred after SVF injection in healthy discs
Summary
A comprehensive number of diseases and degenerative conditions have recently been treated successfully with stromal vascular fraction (SVF), a mixture of various cell types derived from adipose tissue. This heterogeneous cell mixture has been reported to contain endothelial cells, pericytes and hematopoietic cells (monocytes, lymphocytes and granulocytes) [1] (Table 1). Large numbers of erythrocytes are present in this mixture, despite several washing steps (108–109 cells per ml compared to 5 9 109 erythrocytes per ml whole blood). In addition to soft tissue applications such as pulmonary fibrosis [2] and vascular bypasses [3] that have benefited from the healing potential, musculoskeletal research groups have successfully incorporated SVF in their therapies, like for chondromalacia patellae [4]. Our group had thriving experiences with this cell mixture, as demonstrated in goat osteochondral.
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Schedule a callMore From: European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
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