Micronized Fat Transfer utilizes adipose tissue stem cells (ASCs), which are considered a type of mesenchymal stem cell (MSC) found in stromal vascular fractions (SVF) isolated from fat tissue enzymatically.
However, research supporting Micronized Fat Transfer shows through fluorescence-activated cell sorting (FACS) that MSCs and ASCs display different surface marker profiles. In fact, ASCs are a heterogeneous population consisting of adipose tissue-derived stromal cells and MSCs. In SVFs from adipose tissue and bone marrow, Y. Jang et al. identified six major cell types; while adipose tissue contains a significant number of MSCs and ASCs together with a much lower number of leukocyte than those in the bone marrow. In-vitro, ASCs can be differentiated into osteoblasts, chondroblasts, adipocytes, myocytes, and cardiomyocytes in suitable conditions [1, 2 ,3]. Adipose tissue consists of 100–500 folds higher number of stem cells compared to bone marrow, which makes ASCs an attractive source for human usage. ASCs show therapeutic impacts on angiogenesis, wound healing, and the immune regulatory system. Since the first isolation and classification of ASCs in 2001, the studies about ASCs human trials have been increasing year by year starting from 2007 and reaching its peak in 2015 with up to 187 clinical trials using adipose stem cells. There are six trials registered in clinicaltrial.gov in the first quarter of 2019. Most of the studies have been conducted in East Asia, Europe, North America and United States in phase I and phase II for treatment of skeletal diseases, gastrointestinal diseases, skin diseases, nervous disorders, autoimmune diseases, diabetes mellitus, lung and heart diseases. In general, ASCs can be isolated from the collected adipose tissues in patients and directly injected into the wounds, bloodstream, or encapsulated in biomaterials and. implanted in the wounds. Many investigations showed ASCs can increase the healing rate and decrease healing time both in-vitro and in-vivo [4, 5 ,6]. ASCs can directly differentiate into specific cell lineages such as keratinocytes, fibroblast-like cells, and endothelial cells, together with the release of growth factors and cytokines, all that promote angiogenesis, development, migration of fibroblasts, and production of fibronectin and collagen. These results are consistent in 14 clinical trials data (in clinicaltrial.gov datasheet). They showed improvement of healing in chronic ulcers and in the reduction of pain. However, further studies are needed to accurate the role of ASCs in cancer therapy [7]. Besides, ASCs are also used in many types of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and diabetes mellitus [8]. ASCs contribute to maintaining the balance of the immune system by regulation of T-cell as well as IL-10 secretion and activity. The ASCs encapsulated in biomaterials used for plastic surgeries are considered prevalent in East Asian countries. This system promotes wound healing process and reduces the possibility of scar formation or old scar re-emergence upon the body surface.
White adipose tissue (WAT), the primary energy storage tissue in the body, contains significantly higher numbers of adipose-derived stem cells (ASCs) than brown adipose tissue (BAT). Because of this, Micronized Fat Transfer typically relies on ASCs obtained from WAT, although cells from WAT and BAT can show different differentiation characteristics. In clinical applications, ASCs have mostly been isolated from WAT in subcutaneous depots. It is important to develop and optimize ASCs-related technologies such as the harvesting, isolation, and storage of these cells, which are suitable for clinical application. Generally, ASCs can be obtained in SVFs after removing no-adhesion-plastic cells after 24 h culture. The cell population will be classified based on specific markers on cell surfaces by flow cytometry. Quality and quantity of ASCs thus depend on the isolation methods. Interestingly, most studies showed ASCs are heterogeneous population characterized by groups of surface markers, containing MSCs, adipose stromal cells, endothelial progenitors, pericytes and hematopoietic cells. Compared to bone marrow, the number of SVF cells, or even MSCs and ASCs in adipose tissue are 4–6 folds higher, 4.28% for MSCs and 32% for adipose stromal cells respectively in SVFs [16]. The selected markers for classification of ASCs population may vary by investigations [26, 27 ]. ASCs can express MSC marker CD90 and other markers such as CD34, CD73, and CD105 [28], which is consistent with minimal criteria for defining MSCs by the International Society for Cellular Therapy (ISCT) and the International Fat Applied Technology Society (IFATS) [29,30]. According to IFATS, original ASCs can be defined by positive marker CD34 and negative markers CD45, CD235a and CD31; while cultured ASCs expressed CD73, CD90, CD105, CD44 and were negative with CD45 and CD31. The authors pointed out that CD36+/CD106− markers can be used for distinction with bone marrow stem cells [29]. The morphology and gene expression profile of ASCs are similar to other MSCs derived from bone marrow and umbilical cord. Wolfgang Wagner et al. showed 25 up-regulated genes which overlapped between MSCs from different sources and isolation methods [31]. This suggests using 25 defined genes to classify stem cells among others cell population together with cell surface markers by screening method. In the expansion culture, ASCs can achieve the maximum proliferation in 10% Fetal Bovine Serum (FBS) medium or even a mixture of low FBS and separate growth factor medium [32]. ASCs showed similar morphology and differentiation characteristics to MSCs from bone marrow [33]. ASCs can be differentiated into adipocytes, osteoblasts, chondroblasts, hepatocytes, and neuron cells in different conditions [2,3,26,33,34,35,36,37,38]. In addition, ASCs is also going to be senescence; however, this characteristic is varied by patients [33], and it may be a challenge to ASCs researches.
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