Mechanical Micronization of Lipoaspirates: Squeeze and Emulsification Techniques

Sir: With great interest, we have read the article of Mashiko et al., in which the authors compare four different techniques to dissociate lipoaspirates, to obtain a stromal vascular fraction.1 Especially the comparison between the cellular components of two mechanical isolation procedures (either residual tissue of emulsified fat or filtrated fluid of emulsified fat) is interesting, because these two methods of mechanical isolation are similar to the fractionation of adipose tissue procedure (residual tissue of emulsified fat)2 and the nanofat procedure (filtrated fluid of emulsified fat) described by Tonnard et al.3 Procedures for the isolation of stromal vascular fraction or adipose-derived stromal cells from adipose tissue have become a hot topic of research and clinical application. This is because of the presumed regenerative potential of stromal vascular fraction or adipose-derived stromal cells in clinical application. It is obvious that studies such as that by Mashiko et al. are important for determining the reliability and safety of those procedures. However, what is equally important is to reach a uniform nomenclature for “stromal vascular fraction,” which implicates a uniform name for a uniform product. Until now, both enzymatic and mechanically produced fractions from adipose tissue have been called the stromal vascular fraction.4 However, as is shown by Mashiko et al., enzymatic disruption of adipose tissue results in a completely different type of stromal vascular fraction compared with mechanical disruption of adipose tissue. The enzymatic disruption of adipose tissue results in a single-cell suspension in which all cell-cell communications are fully disrupted and the extracellular matrix is digested, and adipocytes are destroyed too. After mechanical isolation, however, adipocytes are also destroyed, but intercellular connections and cell–extracellular matrix connections remain intact.2 Moreover, the extracellular matrix, which is an important reservoir of growth factors and acts as an instructive scaffold in the regenerative processes, remains also intact, in contrast to enzymatically dissociated lipoaspirate. Therefore, we reason that the current nomenclature of both the enzymatically derived fraction of adipose tissue and the mechanically derived fraction of adipose tissue, both called stromal vascular fraction, needs to be refined. According to definitions by pathologists and histologists, stroma of human tissue comprises the connective and structural components of organs in the human body. In essence, stromal tissue is similar in all human organs and consists of connective tissue, blood vessels, and nerves. Connective tissue consists of two important components: cells and extracellular matrix, which consist of protein fibers (primarily collagens) that are embedded in ground substance.5 Ground substance is a hydrophobic viscose complex of, for example, glycosaminoglycans and proteoglycans, which among others binds to integrins of cells and promotes their survival and their function. Furthermore, growth factors are bound to the glycosaminoglycans and proteoglycans of the ground substance and from here on result in controlled release or storage. Release of growth factors results in survival, growth, differentiation, and function of cells present in connective tissue, such as fibroblasts, endothelial cells, mesenchymal stem cells, and immune cell lines.5 In addition, stromal vascular fraction–bound factors instruct the parenchymal cells of organs. When adipose tissue is enzymatically digested, the architecture and instructive capacity of the stromal tissue is fully destroyed, although the isolated stromal tissue cells will survive. We anticipate that the therapeutic function of this enzymatically derived stromal fraction may be compromised compared with normal stromal tissue because of the absence of the matrix component. Besides that, only the cellular component of connective tissue is intact in enzymatically derived stromal fraction, but has been shown to engraft poorly (e.g., in studies of cardiac cell therapy, where retention was low at 24 hours after injection).6 In contrast, after mechanical dissociation of lipoaspirate, much of the infrastructure and function of the stromal fraction remains intact and the retention after administration is expected to be high. To avoid confusion and to make the nomenclature of stromal vascular fraction and its function clearer for both clinicians and researchers, we propose a more precise nomenclature for stromal vascular fraction, based on its phenotype and associated remaining potential function: enzymatically derived stromal vascular fraction should in our opinion better be named “cellular-derived stromal vascular fraction,” and mechanically isolated stromal vascular fraction, that still has a stromal tissue-like structure, should better be named “tissue-like stromal vascular fraction.” Studies like those of Mashiko et al. are further warranted and definitely needed to elucidate differences and characteristics of either cellular-derived stromal vascular fraction or tissue-like stromal vascular fraction. DISCLOSURE None of the authors has a financial interest to declare in relation to the content of this communication. Joris A. van Dongen, B.Sc.Bergman ClinicsRijswijk, The NetherlandsDepartments of Pathology and Medical Biology and of Plastic SurgeryUniversity of Groningen and University Medical Center of GroningenGroningen, The Netherlands Hieronymus P. Stevens, M.D., Ph.D.Bergman ClinicsRijswijk, The Netherlands Martin C. Harmsen, Ph.D.Department of Pathology and Medical BiologyUniversity of Groningen and University Medical Center of GroningenGroningen, The Netherlands Berend van der Lei, M.D., Ph.D.Department of Plastic SurgeryUniversity of Groningen and University Medical Center of GroningenGroningen, The NetherlandsBergman ClinicsHeerenveen and Zwolle, The Netherlands