Our Fat Future: Translating Adipose Stem Cell Therapy

Abstract

Human adipose stem cells (hASCs) have the potential to treat patients with a variety of clinical conditions. Recent advancements in translational research, regulatory policy, and industry have positioned hASCs on the threshold of clinical translation. We discuss the progress and challenges of bringing adipose stem cell therapy into mainstream clinical use.

Significance: This article details the advances made in recent years that have helped move human adipose stem cell therapy toward mainstream clinical use from a translational research, regulatory policy, and industrial standpoint. Four recurrent themes in translational technology as they pertain to human adipose stem cells are discussed: automated closed-system operations, biosensors and real-time monitoring, biomimetics, and rapid manufacturing. In light of recent FDA guidance documents, regulatory concerns about adipose stem cell therapy are discussed. Finally, an update is provided on the current state of clinical trials and the emerging industry that uses human adipose stem cells. This article is expected to stimulate future studies in translational adipose stem cell research.

Figure 1.

The steps of adipose stem cell therapy. Two modes of human adipose stem cell (hASC) therapy are highlighted, and examples of some critical issues at each step are shown (but by no means are all inclusive). In mode 1 of hASC therapy, standardized methods should be developed to prescreen each patient for hASC therapy candidacy and to determine the best method of adipose tissue acquisition (whether resection, liposuction, or an alternative). Because Current Good Manufacturing Practice facilities for hASCs could be located off-site, technologies for shipping hASCs should be optimized. Cell isolation technologies should maximize cellular yield. There will be many issues to consider when manipulating cells, including the high level of hASC variability between donors and the inherently heterogeneous cell population. The development of closed-system devices that continually monitor cells and adjust culture conditions to deliver a consistent hASC output might be especially useful in achieving this goal. In addition, if the patient would prefer to bank cells for future procedures, long-term storage methods must be validated for safety and efficacy. An ideal mode of hASC administration would be both condition-specific and patient-specific. After hASC treatment, standard methods are needed to monitor a patient for adverse side effects. In mode 2, hASCs are isolated, processed, and administered back to the patient at the point of care. This method will require the optimization of closed-system isolation devices and the determination of whether the stromal vascular fraction or hASCs will be the final cell therapy delivered back to the patient.

Figure 2.

Human adipose stem cell (hASC) clinical trials and the emerging global industry. (A): The number of hASC clinical trials registered on clinicaltrials.gov has been gaining momentum for the past decade. As of March 9, 2015, most trials were still in phase I and II (B) and in the process of recruiting (C). (D): In addition to clinical trials, a global industry has emerged. The 25 mapped companies throughout the globe are current leaders within hASC commercialization as identified by hASC-related clinical trials and patents. These companies were identified from either the 152 previously mentioned clinical trials or a U.S. patent search (ABST/(adipose AND stem AND cells) or TTL/(adipose AND stem AND cells)), where ABST indicates “abstract” and TTL indicates “title,” on http://patft.uspto.gov on March 9, 2015. General mesenchymal stem cell patents and patents held by noncommercial institutions were not included within this industry map, although a number of universities and hospitals have also performed clinical trials and hold patents. Company locations and URLs can be found in the supplemental online data. Abbreviation: NA, not available.