Adipose-derived stem cell niche refers to the complex relationships that ADSCs establish with all of the physiological or ectopic factors contributing to determine their identity and fate. The phenotypical identity of any cell and its reaction to a given stimulus are, therefore, not only determined by the genetic or epigenetic equipment of the cell but also depend on the specific niche context in which it resides. A change in niche parameters or the transplantation of cells into other niches can have a considerable effect on cell physiology and alter its properties.

Research has shown that the signal controlling the embryonic origin of ADSCs and their differentiation in adult adipose tissue include the same pathway as that involved in the homeostasis of other adult and embryonic stem cell populations [37, 38], and their complex mechanism can have different effects depending on the concentration, stage of differentiation, and extrinsic niche factors, such as cell-matrix and cell-cell interactions, presence of vasculature, and type of innervation. Despite extensive research about the intracellular signaling involved in ADSC homeostasis and differentiation, little is known about the role of cell-cell and cell-matrix interactions [39, 40].

Zannettino et al. [41] suggested that ADSCs reside in perivascular niches, which prompts the idea that perivascular structures (cells and extracellular matrix) may provide signals that balance the maintenance of ADSCs in an undifferentiated state and their commitment to differentiation. It has recently been shown that in vitro culture significantly alters the transcriptional phenotype of ADSCs. Freshly isolated stromal vascular fractions (SVF) express hematopoietic markers (CD34) that are lost within a few days of culturing [42]. In line with previously published findings [43], the increased expression of mesenchymal stem cell-associated markers in cultures of human and murine ADSCs has been documented, whereas the longer-term loss of markers of undifferentiated status, such as undifferentiated transcription factor (UTF-1), indicates a shift toward differentiation. Prolonged culturing also significantly downregulated various isoforms of procollagen, matrix metallopeptidases, and inflammatory cytokines, thus indicating adaptation to the artificial environment. Under extreme conditions, it has even been reported that in vitro long-term culturing can induce the neoplastic transformation of ADSCs [44], although it is still unclear whether these changes are reversible or how they may affect the therapeutic potential of the cell.

However, ADSCs can be used in many clinical applications (particularly in the fields of plastic and reconstructive surgery) by means of transplantation without removing them from their fat niche. In addition to molecular and cell biology, the dynamic and regenerative nature of fat grafts has been established in various areas of plastic surgery, and clinical practice has shown that long-term outcomes of fat grafting can include rejuvenation of skin texture [45]. Ultrastructural studies of centrifuged fat have revealed that mature adipocytes show interruptions in their cytoplasmic membrane and various degrees of degeneration including cell necrosis, but the stromal vascular fraction (SVF) appears to be well preserved [46].

Rigotti et al. [47] compared the ultrastructure of mammary radiolesions before, and at different times after fat grafting, and found clear signs of regeneration, with evidence of new adipocytes. Before transplantation, almost all of the adipocytes were seriously damaged by centrifugation, and in the radio-damaged recipient tissue, there were neither mature adipocytes nor differentiating preadipocytes. Reasonable interpretations of these findings are that the differentiating preadipocytes observed after treatment were either committed adipocyte originally embedded within the transplanted fat or endogenous locally present committed adipocyte, activated by the ectopically transplanted fat. The massive survival of ADSCs in fat transplants, despite liposuction and centrifugation procedures, strongly supports the first hypothesis, but the second may be equally valid as it assumes that transplanted fat enriched with ADSCs by centrifugation can behave as an atypical ectopic niche that direct tissue regeneration by modulating endogenous tissue resources.

The term “atypical ectopic niche” could be used as a common paradigm of stem cell-based therapies. It is based on the idea of a “bystander” mechanism in which the stem cells ectopically transplanted into a generic lesion (radiolesion, myocardial infarction, cerebral stroke, etc.) do not replace tissue-specific cells by direct differentiation, but locally form an atypical stem cell niche that suppresses inflammation, promotes neo-angiogenesis, and favors the activation of endogenous stem cell precursors by releasing trophic factors, such as cytokines, proangiogenic molecules, and growth factors. Therefore, adipose tissue can be considered an ideal “biologic product” [48]. The role of this essential component of the stromal fraction of the lipoaspirates argues for a regenerative theory based on angiogenesis imbued by various growth factors, not yet fully identified, released from stem cells. Thus, in addition to the traditional understanding that fat is a high-energy reservoir involved in homeostasis for its ability to bind large amounts of fluids and in the maintenance of thermoregulation, it becomes apparent that it is also a regenerative organ providing the basis for soft tissue regeneration.

According to the sub-mentioned theories, nowadays ADSCs have become one of the most popular adult stem cell populations for research in soft tissue engineering and regenerative medicine applications. Compared with other stem cell sources, they offer several advantages including an abundant autologous source, minor invasive harvesting (liposuction), significant proliferative capacity in culture, and multi-lineage potential. To harvest the adipose tissue, a liposuction procedure is less invasive than bone-marrow aspiration, and the technique produces less patient discomfort and donor site morbidity. Small amounts of adipose tissue yields approximately 5 × 10³ stem cells, which is 500-fold greater than the number of MSCs in 1 g of bone marrow [49].

Numerous preclinical studies have been pursued, with early clinical data appearing in the literature. Fat as a living, free graft does more than just fill the area into which it is placed. Grafted fat affects the tissue into which it is placed in many ways for the life of the patient. It can improve the quality of aged and scarred skin and heal radiation damage and chronic ulcers. Just how grafted fat causes these changes remains unanswered. We know that fat can perform amazing feats in a glass tube and in some animal models, but we have little insight into what happens to fat when it is grafted from one part of the human body to another part. The focus of the near future should be research to explain and expand on future clinical successes.

In addition to the outstanding results of lipotransfer for volume restoration, surgeons have become increasingly interested in the apparent rejuvenative effects on the skin itself. Coleman has noted improved skin quality, with softening of wrinkles, decreased pore size, and improved pigmentation during the first year posttreatment. In fact, analysis of clinical results following both reconstructive and aesthetic surgery reveals that after one or several repeated fat grafting procedures, the trophicity and quality of the recipient site is improved. These changes develop over several months following the fat grafting procedure, with a variable expression, as improvements in skin texture, skin suppleness, skin color, and/or scar quality.

Topographical skin analysis systems such as the recently developed VISIA system (Canfield Imaging Systems) may determine whether the effect from fat grafting is an effective skin rejuvenation technique in comparison to chemical peels and laser resurfacing. Aside from effects on normal, aged skin, when fat has been grafted beneath depressed scars, there was improvement not only in the depression but also in the character of the scar itself, with an apparent transformation to normal-appearing skin. Other authors have reported an adverse range of improvements in soft tissue conditions, including radiation damage, breast capsular contracture, damaged vocal cords, and chronic ulceration, as well as regrowth of calvarial bone. While many of the exact mechanisms for these effects remain to be described, what seems to be at the center of these changes is the presence of adipose-derived stem cells (ASCs).

The possible application of ADSCs for tissue repair and healing has recently been researched. It has been experienced that

These therapeutic models may be applicable to clinical situations in which the environment for wound healing is compromised by inadequate blood supply and severely scarred tissue. Gimble et al. have shown that ASCs delivered into an injured or diseased tissue may secrete cytokines and growth factors that stimulate recovery in a paracrine manner. ADSCs modulate the stem cell niche of the host by stimulating the recruitment of endogenous stem cells to the site and promoting their differentiation along the required lineage pathway. In a similar way, ADSCs could provide antioxidants, free radical scavengers at an ischemic site: as a result, toxic substances released into the local environment would be removed, thereby promoting recovery of the surviving cells [23]. Further preclinical and clinical studies need to be performed so that ADSC-based therapies fulfill expectations and can be successfully used to treat disorders for which the present medical and surgical therapies are either ineffective or impractical.

Atrophy is the defining feature of aging: it also represents a primary challenge in the evolving quest to find the best approach for rejuvenating aging faces and bodies. Rejuvenation is not about suspension or sagging: it is all about augmentation in order to restore youthful fullness and contour in a natural and aesthetic fashion. One major goal of rejuvenation procedures is to rebalance fat and restore harmony to the face. This can be accomplished by microliposuction of the fatty “hills” and fat transfer to the sunken “valleys.” Restoration of homogeneity to the facial structure reduces the sharp shadows associated with aging.

Augmentation represents the past and the future of rejuvenation. It also holds the key to possible new developments such as tissue repair. Examination of the results over time reveals promising posttreatment changes in the quality of the patient’s skin after the placement of grafted fatty tissue under it. In addition to restoration of youthful contours, intrinsic qualities of skin texture, elasticity, and color return to a more youthful state for an extended period of time. Stem cells have been shown to be present in significant quantities in harvested fatty tissue. Perhaps they are mending the sun-damaged, aging epithelium.

Sagging of the aging face may occur mostly as a result of changes in the fat compartments that are coincident with chronological aging. Localized overabundance of fat may weigh down the tissue. Conversely, an area devoid of fat resembles a deflated balloon by inducing the downward displacement of facial skin. Inelastic recoil due to photodamage compounds this effect. If altered fat distribution underlies differences between the young and the old face, a new model for the youthful countenance might arise.

A young face has a smooth, ample distribution of fat. It resembles a continuous, “gently rolling plain” because the fat is evenly distributed. There is a forward projection with facial arcs highlighting specific areas and causing minimal shadow. In contrast, the aging face has “hills and valleys” producing deep shadows and irregular highlights. In thin individuals, these “hills” of fat may be minor, but in most middle-aged adults, the hills occur in a strip down the central face from mid-cheek to jowl, along the nasolabial and labiomental folds. Fat pocketing can also be seen suborbitally on the lateral zygoma, submentally, and along the neck platysmal bands. Since body fat rises with age, so does facial fat. “Valleys,” in contrast, occur periorbitally and periorally, in the malar, buccal, and temporal areas and on the far lateral cheek.

Fat loss manifests around the mandible and throughout the forehead and scalp. The most common areas of the face which are treated with autologous fat grafts include the nasolabial groove, marionette lines, midface, and lips. Autologous fat performs best in the midface area considering the longevity compared to other more mobile areas such as the lips and marionette grooves.

The most common modality the authors use for harvesting fat is local anesthesia with sedation. There have been concerns about the effect of local anesthetics such as lidocaine on the viability of fat grafts harvested by any kind of liposuction since such an agent is routinely used for analgesia of the donor site. Such a concern is based on an in vitro study reported by Moore et al. that lidocaine may inhibit a variety of adipocyte functions in tissue culture. However, the effect is found to be totally reversible once the agent has been washed out [52]. The viability and differentiation of preadipocytes are also found to be impaired but only after being isolated from fat tissue and then exposed directly to a higher concentration of lidocaine (2 %) in vitro for 30 min. The effect is thought to be independent of lipophilic properties and the resulted in vivo concentration of lidocaine may be different due to dilution effects [53]. However, Shoshani et al. [54

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