Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events

Abstract

The popularity of adipose‐derived cell therapy has increased over the last decade, and the number of studies published annually is growing. However, concerns regarding safety in the setting of previous malignancy or the use of allogeneic cells have been raised. We therefore aimed to systematically review all clinical studies using adipose‐derived cell therapy to identify reported adverse events with a special focus on risk of thromboembolic, immunological, and oncological safety concerns. Our systematic search resulted in 70 included studies involving more than 1,400 patients that were treated with adipose‐derived cell therapy. Safety assessment method was not described in 32 of the included studies. For studies involving systemic or cardiac administration, one case of pulmonary thromboembolism and cases of both myocardial and cerebral infarctions were described. In the setting of allogeneic cell therapy studies, where the production of specific antibodies toward donor cells was examined, it was noted that 19%–34% of patients develop antibodies, but the consequence of this is unknown. With regard to oncological safety, only one case of breast cancer recurrence was identified out of 121 patients. Adipose‐derived cell therapy has so far shown a favorable safety profile, but safety assessment description has, in general, been of poor quality, and only adverse events that are looked for will be found. We encourage future studies to maintain a strong focus on the safety profile of cell therapy, so its safeness can be confirmed. stem cells translational medicine 2017;6:1786–1794

Isolation of adipose tissue derived regenerative cells from human subcutaneous tissue with or without the use of an enzymatic reagent

“…Of note, when using UA-ADRCs during a surgical procedure in an autologous and homologous way, they are not considered an advanced therapy medicinal product (ATMP) by the European Medicines Agency [28]. In contrast, expansion of ASCs in vitro may be associated with risks such as possible loss of stemness or cell transformation [29][30][31]. On the other hand, recent studies on culture systems and animal models indicated noninferiority or even superiority of UA-ADRCs over ASCs in, for example, rescuing heart function after acute myocardial infarction [32], bone regeneration [33] and erectile function recovery after cavernous nerve injury [34] (see also [13]).…”

Non-invasive imaging reveals conditions that impact distribution and persistence of cells after in vivo administration

“…Mesenchymal stem/stromal cells (MSCs) isolated from bone marrow, adipose tissue or umbilical cord are being tested in clinical trials for a range of conditions, but in many cases, preclinical safety data are not available, and the authors fail to report whether the cells cause any adverse effects. Bone marrow-derived MSCs have been used for many years and appear safe [3], but a review of adipose-derived MSCs concluded that while adverse events are rare, they nevertheless do occur, and are likely to be related to underlying health conditions of the patients or administration route [4]. Human umbilical cord-derived (hUC)-MSCs have only recently been introduced in clinical trials, with more than 50% of these initiated within the last 3 years (a summary of registered trials in presented in Additional File 1).…”

In vivo fate of free and encapsulated iron oxide nanoparticles after injection of labelled stem cells

“…Encapsulation of SPIONs resulted in a drop in solution relaxivity due to hindered access to the solution water protons and is similar to the previous findings of the entrapment of free particles inside the lysosomes. 20,22,32 Cell labelling efficiency and toxicity of SPIONs mMSCs were chosen for this study because they are similar to human bone marrow derived mMSCs which are being used in clinical trials, 41,42 and it has already been shown that these cells uptake free SPIONs and other nanoparticle probes with good efficacy. 12,22 To evaluate the cell labelling efficiency and toxicity of free and encapsulated SPIONs, cells were labelled with suspensions of particles (encapsulated or free) having comparable Fe content.…”

“…5,42,44 Due to the impact on the interpretation of imaging results and particles' associated toxicity, it is important to see the fate of particles once labelled cells die. Hence, soon after injecting the labelled mMSCs into mice, their in vivo bio-distribution was monitored in parallel by BLI and MRI for 14 days.…”