Purpose
Adipose stem cells have an important place in research and clinical applications, and it is particularly important for clinicians to distinguish between adipose grafting and adipose stem cells and to understand the connection between the two. It is easy to confuse the two in the clinic. The purpose of this article is to clearly distinguish between fat grafting and adipose stem cell therapy as well as the processes, outcomes, and complications of adipose stem cell extraction, processing, and application. The findings show that autologous fat grafting is widely used to fill soft tissues and treat tissue volume loss due to disease, tumors, congenital malformations, and natural aging, on the other hand, adipose stem cells have been recognized as a good cellular resource in regenerative medicine that can increase the survival rate of fat grafts during the fat grafting process, and studies show that adipose stem cells have great promise for application, but a lot of research is still needed.
Definition
Fat grafting is the process of re-enlargement of missing soft tissue. Fat grafting is considered to be the least destructive procedure because it is autologous and non-carcinogenic, and it is easy to obtain and scar less easily in the recipient area, so it is often an alternative to dermal fat grafting, local flaps, arbitrary flap grafts, allografts, and injectable material fillings. However, fat fillings are prone to deformation and unpredictable resorption, which may lead to reoperation.
In the laboratory and in the clinic, adipose stem cells have been used to treat wounds that are difficult to heal, to heal radiation burns, and to increase the viability of fat grafts. In addition, adipose stem cells are also used in other specialized areas such as damaged cardiomyocytes, vascular endothelial grafts, and bone tissue engineering.
Although adipose stem cells can increase the survival of autologous fat grafts, improve vascular regeneration in mastectomy breast reconstruction, and studies have indicated that adipose stem cells increase the stimulation of tumor cell growth, but not in quiescent tumor cells. However, it is worth noting that in the application of adipose stem cells to breast reconstruction, it is important to confirm that the residual tumor cells are in the quiescent phase. Clinicians should consider the clinical limitations nowadays and so far due to the limitation of clinical trials, more studies must discern other potential complications that may arise in adipose stem cell enriched fat grafts.
Applications
Investigations have shown that adipose stem cells are readily available and a renewable resource with profound implications for soft tissue repair as well as regenerative cell therapy. Clinical trials and case reports of adipose stem cells in soft tissue, orthopedics and immunology, with indications in Europe and Asia have been published. The U.S. Food and Drug Administration is still conducting research in this area, and the most important aspect of future research on adipose stem cells, both basic and clinical, is to clarify that adipose stem cell-rich fat grafts are safe and effective. In addition, long-term research results are needed before fat stem cells can be accepted, such as prediction of outcomes, graft survival, simplification of procedures, cost and aesthetic results compared to traditional methods.
Adipose stem cells can be used not only in soft tissue aesthetic and reconstructive surgery, but also in internal medicine, neurology, and orthopedics. Adipose stem cells grown in biological scaffolds can be used in soft tissue repair because adipose stem cells are stromal cells that can grow inside the scaffold, where the cells adhere, add value and differentiate.
Adipose stem cells are isolated from adipose tissue stromal vessels. A standard unprocessed adipose tissue is composed of mature adipocytes, extracellular matrix, adipose stem cells, endothelial cells, and wall cells. When digested with enzymes, cell fragments are formed from the adipose stromal vascular fraction containing adipose stem cells, vascular progenitor cells, pericytes, and endothelial cells. Although adipose stem cells are actually mesodermal, they can potentially differentiate into adipocytes, osteoblasts, chondrocytes, myoblasts, mesenchymal cells, and neural progenitor cells under appropriate conditions. Recently it was reported that adipose stem cells can differentiate into ectodermal and endodermal tissues such as neuronal cells, hepatocytes, pancreatic islet cells, endothelial cells, and epithelial cells. The most favorable advantage of these mature stem cells is that they are easily obtained from adipose tissue, extracted at ratios from 1:100 to 1:1500, much higher than other multifunctional cells and 500 times higher than the ratio of MSCs extracted from bone marrow. One gram of adipose tissue yields approximately 5,000 adipose stem cells.
Indications
Fat grafting is indicated for any asymmetry and lack of soft tissue due to age-related causes, infections, trauma, progressive facial deviation atrophy, craniofacial shortening, etc. Some clinicians have used large amounts of fat for breast reconstruction, and although controversial, fat grafting is being used to correct breast deficiencies going to and in breast reconstruction for cancer removal. It has been recently reported that fat grafting has been used to treat radiation injury, breast envelope contracture, damaged vocal cords, and chronic ulcers.
Adipose stem cells have potential applications in regenerative medicine that could also increase the activity of fat grafts. In the United States, adipose stem cell-rich grafts have been applied in product development and tissue engineering, as more data are needed to support his clinical application. In particular, adipose stem cells are being investigated as a treatment for wounds. It has been used abroad as a treatment for facial atrophy, breast augmentation, and perianal fistula treatment. In experimental murine models of myocardial infarction adipose stem cells can increase neovascularization, increase wall thickness, and myocardial remodeling effects. In experimental rats, fat grafts mixed with adipose stem cells had greater survival than fat grafts alone. In addition, adipose stem cells improved the treatment of disc degeneration by restoring type II collagen showing that adipose stem cells potentially restore degenerated discs.
In 30 cases in the last 3 years, adipose stem cell-rich fat grafts were used in many cases, including polio, Parieberg’s disease, breast reconstruction, scars, and soft tissue loss in the buttocks. Other preclinical animal studies are cranial and long bone loss spinal fusion, stroke, spinal trauma, multiple sclerosis, clone disease, bone marrow stem cell transplantation, osteoarthritis, liver reconstruction, type 1 diabetes, acute ischemia, etc.
Because adipose stem cells are progenitor cells, they are prohibited for patients with a history of tumor disease. In one project study, adipocytes mixed with prostate cancer cells injected into mice increased the growth rate of tumors. However, in another project, adipose stem cells in a breast cancer model accelerated their growth except in the quiescent phase. It must be clearly understood that this is only an animal study and there are no comparative human studies. The Oxford University evidence-based medical study suggests that adipose stem cell therapy is now considered a grade D treatment and there is not enough evidence to weigh the pros and cons.
Transplantation
The fat grafting injection technique is to mark the defective area to be filled to the recipient bed and survived. The fat graft is received in such a way that the transplanted fat cells survive within 2 mm of the arterial vascular tropism and may necrotize and cause scarring if they are beyond the tropism. Fat is injected by first forming an injection tunnel with a blunt needle and then injecting small amounts with a syringe back method, most injections are done in a fan shape, fat grafting is injected into the defective area at different depths through several points around the injection, the surgeon mostly uses an over-injection of 20-30% beyond the defective amount as there is no way to estimate the amount of fat absorption. The remaining fat is kept frozen for up to 6 months after the procedure, but due to the overly cold conditions may cause its reuse to be ineffective.
Adipose stem cells can be mixed with adipocytes and then injected into the subcutaneous adipose and muscle layers by different injection orientations, and in tissue engineering, adipocytes are inoculated into the dermal matrix or collagen matrix as seed cells, or in a bioreactor using tissue engineering techniques.
Conclusion
Early reports of autologous fat grafting reported only 45% residual at one year after fat grafting. In recent studies, the surgical grade changed from II to III, and the postoperative resorption rate ranged from 30% to 70%. The overall process of fat grafting is assessed by observational reports, palpation, and photographs, while objective methods such as laser scanning, 3D imaging, and nuclear magnetic imaging are now used in outcome assessment.
Rough techniques in obtaining fat cells can lead to apoptosis, and the viability of the fat in the recipient area is also related to the vascular supply in different areas, as well as to the centrifugal speed of the fat cells, and other factors including donor age, recipient area, scars, radiation sites and preparation methods.
The results of the adipose stem cell study are also ongoing and the findings are promising but still lacking scientific support. A controlled randomized class I study is needed but is still not available. In a few cases, adipose stem cells have been shown to promote wound healing and enhance fibrosis formation in radiation wounds. In addition, in a class III case-control study, adipose stem cells mixed with adipocytes for filling were much more effective than fat grafting alone. The application of adipose stem cells may enhance vascular regeneration, improve graft survival, and reduce atrophy. Yoshimura used fat grafts with adipose stem cells to treat facial fat atrophy, and animal studies based on this showed that the survival rate of fat grafts containing adipose stem cells was higher than that of fat grafts without adipose stem cells, and showed that the vascular component of the fat matrix contained more vascular endothelial cells. Yoshimura performed breast augmentation with fat with adipose stem cells and the breasts still maintained good volume after 5 years.
Also a large number of experimental studies with adipose stem cells, including massive soft tissue loss, radiation injury, facial atrophy, and breast augmentation. Current National Institutes of Health clinical trial registry patients include: adipocyte transplantation for patients with fat metabolism disorders, patients with clonal disease, diabetic lower extremity ischemia, and bone grafting using adipose stem cells as seed cells for scaffolding.