Adipose tissue-derived stem cells: can impure cell preparations give pure results?

Stem cells are undifferentiated cells defined by their ability for self-renewal and the capacity for multi-lineage differentiation. Over the last decade, there has been a growing interest in the use of stem cells to restore organ function, including renal failure. Biotechnology companies have also picked up on this scientific development, which is an essential step in development towards clinically applicable cell therapy products. Unfortunately, unregulated commercial exploitation of the scientific potential of stem cell therapy occurs as well, and careful scientific evaluation of its benefits and potential risks is warranted [1]. Currently, there is no universal source for stem cells available. Embryonic stem cells (ESc) exhibit unlimited differentiation potential both in vitro and in vivo, and thus would constitute the ultimate source for generation of various tissues. However, they are subject to significant legal, ethical and political concerns [2]. In addition, teratoma formation is a critical obstacle to safe clinical translation of human ESc-based therapies in the future. Another interesting cell type for possible future therapeutic applications is the induced pluripotent stem (iPS) cell. These are differentiated cells that are reprogrammed to stem cells by introducing a set of embryological transcription factors that results in (epi)genetic reprogramming of the cell [3]. However, similar to the use of ESc, the risk of malignant transformation has been shown to be high in iPS cells, while results in rodents may be difficult to translate to human cell reprogramming [3]. Therefore, the development of current therapies is mostly limited to progenitor cells isolated from adult tissue, which in comparison with totipotent stem cells have more specialization and less differentiation potential [4,5]. These cells include haematopoietic stem cells (HSCs), bone marrow-derived mesenchymal stromal cells (BM-MSCs), endothelial progenitor cells (EPCs) and adipose tissue-derived mesenchymal stromal cells (AT-MSC). Encouraging results have in particular been obtained with BM-MSCs in both pre-clinical and early-phase clinical studies, and >100 trials have been registered so far for a wide range of indications including graft-versus-host disease, osteogenesis imperfecta, myocardial infarction, systemic lupus erythematosus and diabetes [6,7]. A big challenge with the development of MSCs as a clinical therapy is the requirement to culture and expand these cells for 3–5 weeks, which necessitates technological advanced facilities and procedures, while the culture procedure may also change the phenotype and function of MSCs. Recently, adipose tissue has been identified as a novel and rich source of MSCs (AT-MSCs). AT-MSCs appear to be different from BM-MSCs in that they exhibit a different immune phenotype and a higher proliferative potential. In addition, the numbers of MSCs that can be generated from adipose tissue are higher than those that can be isolated from bone marrow. AT-MSCs can therefore be generated in a shorter time period, facilitating their clinical application. It is still largely unknown, however, to what extent the functional properties of these cells are different from BM-MSCs. In this journal, Feng et al. take this concept one step further by investigating the potential for renoprotection of freshly isolated, uncultured adipose tissue cell extract that can be isolated in real time in sufficient quantity to apply for therapeutic applications without ex vivo expansion using the elegant CellultionTM system (Cytori Therapeutics) [8]. Depending on the method of cell isolation and harvesting, ~10–10 final cell therapy products per gram tissue can be obtained within 1–2 h. Time-consuming invasive protocols, which carry a risk of culture contamination and/or genetic modification with possible malignant transformation, are not necessary with this method [9–11]. In addition, there is no need of using culture serum (including fetal calf serum), whichmay be associated with the transmission of disease and antibody formation. Strikingly, both the fresh and cryopreserved isolates can alleviate ischaemia– reperfusion injury in rats. Despite these fascinating observations, there still remain fundamental uncertainties regarding the use of adipose tissue-derived cell product harvested by this method. One of the biggest concerns may in fact be the heterogeneous nature of the cell product. The cell isolate is coined adipose tissue-derived stem and regenerative cells (ADRCs) by the authors [8]. Although MSCs and other progenitors may be in the cell product, the final cell product will contain a mixture of cells including fibroblasts, endothelial cells,