Non-homologous use of adipose-derived cell and tissue therapies: Osteoarthritis as a case study.

Adipose tissue is widely recognized as an abundant and accessible human tissue that serves as a source of cells and extracellular matrix scaffolds for regenerative surgical applications. Increasingly, orthopedic surgeons are turning to adipose tissue as a resource in their treatment of osteoarthritis and related conditions. In the U.S., the regulatory landscape governing the orthopedic surgical utilization of autologous and allogeneic adipose tissue remains complex. This manuscript reviews the Food and Drug Administration's nomenclature and guidance regarding adipose tissue products. Additionally, it surveys recent pre-clinical and clinical trial literature relating to the application of adipose-derived cells and tissues in the treatment of osteoarthritis.

Clinical Efficacy of Intra-articular Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis: A Double-Blinded Prospective Randomized Controlled Clinical Trial.

BACKGROUND: Currently, there are limited nonoperative treatment options available for knee osteoarthritis (OA). Cell-based therapies have emerged as promising treatments for knee OA. Autologous stromal vascular fraction (SVF) has been identified as an efficient medium for intra-articular administration of progenitor cells and mesenchymal stem cells derived from adipose tissue. HYPOTHESIS: Patients receiving intra-articular SVF would show significantly greater improvement than patients receiving placebo injections, and this improvement would be dose dependent. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This was a multisite prospective double-blinded randomized placebo-controlled clinical trial. Adult patients with symptomatic knee OA were eligible. Thirty-nine patients were randomized to high-dose SVF, low-dose SVF, or placebo (1:1:1). SVF was obtained via liposuction, processed to create the cellular implant, and injected during the same clinical visit. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and magnetic resonance images were obtained preoperatively and at 6 and 12 months after injection. The Wilcoxon rank sum nonparametric test was utilized to assess statistical significance, and the Hodges-Lehmann location shift was used to assess superiority. RESULTS: The median percentage change in WOMAC score at 6 months after injection for the high-dose, low-dose, and placebo groups was 83.9%, 51.5%, and 25.0%, respectively. The high- and low-dose groups had statistically significant changes in WOMAC scores when compared with the placebo group (high dose, P = .04; low dose, P = .02). The improvements were dose dependent. The median percentage change in WOMAC score from baseline to 1 year after injection for the high-dose, low-dose, and placebo groups was 89.5%, 68.2%, and 0%, respectively. The high- and low-dose groups displayed a greater percentage change at 12 months when compared with the placebo group (high dose, P = .006; low dose, P = .009). Magnetic resonance image review revealed no changes in cartilage thickness after treatment. No serious adverse events were reported. CONCLUSION: Intra-articular SVF injections can significantly decrease knee OA symptoms and pain for at least 12 months. The efficacy and safety demonstrated in this placebo-controlled trial support its implementation as a treatment option for symptomatic knee OA. REGISTRATION: NCT02726945 (ClinicalTrials.gov identifier).

Regenerative Cells for the Management of Osteoarthritis and Joint Disorders: A Concise Literature Review.

As the global population ages, the prevalence of osteoarthritis (OA) and joint disorders represent a major cause of disability and a significant public health burden. As current approaches for the management of OA focus on slowing the progression of disease, without repairing the underlying damage, novel treatments are necessary to improve outcomes. Over the past decade, autologous cell-based therapies using regenerative cells from fat or bone marrow have become a major focus of research into new approaches for the treatment of osteoarthritis and joint disorders. This review is intended to summarize findings in existing literature and identify gaps in knowledge that should be addressed in order to advance the field. We acknowledge that some findings may appear inconsistent, but show that apparent inconsistency in the literature may be attributable to variation in source of cells, stage of disease, method of delivery, follow-up time, evaluation method, and a number of other idiosyncrasies of individual studies. Still, a number of themes emerge from the data and some broader conclusions may be drawn that can be used to guide future studies. Ultimately, we conclude that there is overwhelming evidence demonstrating the safety of the autologous cell-based therapies. Furthermore, the data support the claim that regenerative cells are capable of reversing progression of OA. Regenerative cells, and especially those from adipose tissue, represent a promising new approach for the treatment of OA. Future work should include appropriate controls, and focus on answering questions related to dose required, appropriate delivery vehicle, and the impact of multiple treatments. Additionally, future studies should look at short and long-term effects of the treatments, and use functional as well as radiologic methods to evaluate efficacy.

Autologous fat processing via the Revolve system: quality and quantity of fat retention evaluated in an animal model.

BACKGROUND: Currently, fat graft viability and retention cannot be reliably predicted. The reasons for this variability are not fully understood, although fat processing has been implicated. OBJECTIVES: The authors compare the in vitro quantity and in vivo fat retention from lipoaspirate processed by the Revolve system (LifeCell, Bridgewater, New Jersey) compared with centrifugation and decantation. METHODS: Ten patients were enrolled in this prospective study. Lipoaspirate from each patient was processed by each of 3 methods: decantation, centrifugation, and the Revolve system. Biochemical characteristics and free oil, adipose, and aqueous phases of the processed fats were determined. Fat grafts were implanted in nude mice; volume retention and quality of the fat grafts were evaluated after 28 days. Viability of retained fat was demonstrated by intact adipocytes and neovascularization on histology. RESULTS: Of the 10 patients, 9 were women and 1 was a man. Mean patient age was 40.7 ± 8.9 years (range, 30-55 years). Fat tissue obtained from all methods had good physiological properties with neutral pH and isotonic salt concentrations. The Revolve system yielded significantly less blood cell debris, a higher percentage of adipose tissue, and a lower percentage of free oil compared with the other 2 methods. Fat tissue retention from Revolve samples was significantly higher (73.2%) than that from decanted samples (37.5%) and similar to that from centrifuged samples (67.7%). CONCLUSIONS: The Revolve system produced physiologically compatible, preinjection fat with reduced contaminants and free oil in conjunction with high fat content. In an animal model, volume retention of Revolve-processed fat grafts was significantly greater than decanted samples. The Revolve system presents a fat-processing option that was less time-consuming, easier to use, and more efficient in this study than standard centrifugation or decantation.

Risks associated with "components separation" for closure of complex abdominal wall defects.

The reconstruction of complex abdominal wall defects can often pose a significant challenge to surgeons and their patients. Complex ventral hernias may result from large tumor resections, trauma from gunshot wounds, or infections following routine abdominal surgery. "Components separation" of the abdominal musculature uses advancement of local autologous tissue, when available, to close large ventral wall defects. The authors report on a retrospective chart review of 30 patients who underwent components separation for the closure of complex abdominal defects. The study group was 50 percent female, with a mean age of 45 years, body mass index of 33.2 kg/m2, and abdominal defect size of 240 cm2. On average, 20 percent of patients had preoperative wound infections, 30 percent had intraoperative bowel enterotomies, and 33 percent required prosthetic mesh for closure. Total surgery time averaged 4.8 hours, with a mean postoperative stay of 12.5 days and follow-up of 9.5 months. The recurrence rate was 10 percent; postoperative complications included midline ischemia, infection, and dehiscence occurring at rates of 20, 40, and 43 percent, respectively. This study provides a comprehensive review of the risks and complications associated with the treatment of complex ventral hernias and those associated with abdominal "components separation."

Adult facial growth: applications to aesthetic surgery.

BACKGROUND: Reshaping of the face with age is a result of volume change and loss of support. It is not well understood which tissues are involved in this process. Recent publications suggest that adult bone growth may have a significant role. OBJECTIVE: We report a longitudinal cephalometric analysis of midfacial growth in adults to determine the role of bone in facial aging. METHODS: The Behrents modification of the Bolton Cephalometric study in patients up to age 83 was reviewed. A trigonometric analysis targeted orbital and anterior maxillary growth. RESULTS: Facial bone growth is shown to continue throughout adulthood. Anterior descent creates increased bone projection. CONCLUSIONS: The appearance of facial aging is caused by attrition of soft tissue volume and loss of support. The deficiency of maxillary bone projection seen in some patients, with tear trough depression and negative vector eyelid (polar bear), preexists adulthood and is unmasked with age.