Adipose-derived regenerative cell (ADRC)-enriched fat grafting: optimal cell concentration and effects on grafted fat characteristics

Journal of Translational Medicine, Oct 2013

Background To overcome the absorption of traditional fat grafting, techniques for adipose-derived regenerative cell (ADRC)-enriched fat grafting are currently being adapted for practical application. The Celution®800/CRS (Cytori Therapeutics, San Diego, CA) has enabled rapid grafting of the patient’s own freshly harvested ADRCs without requiring a culturing step. However, the optimal cell concentration and the effects of ADRCs on the characteristics of grafted fat after free fat grafting remain unclear. Methods ADRCs were isolated and purified from human fat tissue using the Celution®800/CRS. Animals that received fat grafting without the addition of ADRCs were designated the control group (group A). The number of ADRCs per grafted fat volume (mL) was adjusted to 3 × 105, 1.5 × 106, and 3 × 106 cells/mL (groups B, C, and D, respectively), mixed with free fat, and transplanted as ADRC-enriched fat grafting. These mixtures were transplanted subcutaneously into BALB/C Jcl-nu/nu mice. The volume of grafted fat was determined 5 months after transplantation, and histological assessments were performed. Results ADRC-enriched fat grafting resulted in decreased fat absorption and the formation of greater numbers of new blood vessels in the grafted fat. The optimal ADRC concentration in this study was found to be 3 × 105 cells/mL (group B), with higher concentrations resulting in increased cyst and fibril formation in the grafted fat. Conclusions This study used the Celution®800/CRS for free fat grafting and demonstrated that the concentration of transplanted ADRCs affected the engraftment and quality of the grafted fat.

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Adipose-derived regenerative cell (ADRC)-enriched fat grafting: optimal cell concentration and effects on grafted fat characteristics

Journal of Translational Medicine Adipose-derived regenerative cell (ADRC)- enriched fat grafting: optimal cell concentration and effects on grafted fat characteristics Natsuko Kakudo 0 Yoshihito Tanaka 0 Naoki Morimoto 0 Takeshi Ogawa 0 Satoshi Kushida 0 Tomoya Hara 0 Kenji Kusumoto 0 0 Department of Plastic and Reconstructive Surgery, Kansai Medical University , Osaka , Japan Background: To overcome the absorption of traditional fat grafting, techniques for adipose-derived regenerative cell (ADRC)-enriched fat grafting are currently being adapted for practical application. The Celution800/CRS (Cytori Therapeutics, San Diego, CA) has enabled rapid grafting of the patient's own freshly harvested ADRCs without requiring a culturing step. However, the optimal cell concentration and the effects of ADRCs on the characteristics of grafted fat after free fat grafting remain unclear. Methods: ADRCs were isolated and purified from human fat tissue using the Celution800/CRS. Animals that received fat grafting without the addition of ADRCs were designated the control group (group A). The number of ADRCs per grafted fat volume (mL) was adjusted to 3 105, 1.5 106, and 3 106 cells/mL (groups B, C, and D, respectively), mixed with free fat, and transplanted as ADRC-enriched fat grafting. These mixtures were transplanted subcutaneously into BALB/C Jcl-nu/nu mice. The volume of grafted fat was determined 5 months after transplantation, and histological assessments were performed. Results: ADRC-enriched fat grafting resulted in decreased fat absorption and the formation of greater numbers of new blood vessels in the grafted fat. The optimal ADRC concentration in this study was found to be 3 105 cells/mL (group B), with higher concentrations resulting in increased cyst and fibril formation in the grafted fat. Conclusions: This study used the Celution800/CRS for free fat grafting and demonstrated that the concentration of transplanted ADRCs affected the engraftment and quality of the grafted fat. - Introduction Autologous free fat grafting is a widely accepted technique used for the correction of various soft-tissue defects because it is biocompatible, versatile, natural-looking, nonimmunogenic, inexpensive, and readily obtainable with low donor site morbidity [1,2]. Although free fat grafting is used as a method for soft tissue reconstruction, absorption of the fat after grafting is problematic. Free fat grafting often has a low survival rate, and adipose tissue can be quickly resorbed and replaced by fibrous tissue and oil cysts [3,4]. To overcome this shortcoming of traditional fat grafting, techniques for adipose-derived regenerative cell (ADRC)-enriched fat grafting are currently being adapted for practical application. ADRCs are a heterogeneous or mixed population of cells found in adipose tissue by collagenase digestion [5]. This population includes adult stem cells, endothelial progenitor cells, endothelial cells, vascular smooth muscle cells, and leukocytes [5]. Recent studies that have investigated fat grafting enriched with cultured ADRCs have indicated that the technique may be valid and reproducible, and it may result in increased graft viability as assessed by improved transplant volume and histology [6,7]. The Celution800/CRS (Cytori Therapeutics, San Diego, CA) was recently developed to enable rapid grafting of the patients own freshly harvested ADRCs by automating and standardizing the extraction, washing, and concentration of ADRCs for clinical use without requiring a culturing step [5]. The risk of infection and degeneration was shown to be very low because no culture was necessary, and establishing a new cell processing center (CPC) was also unnecessary. Accordingly, no cost for maintenance or labor is necessary, which makes it superior for cost performance, and a delivery platform for regenerative medicine can be prepared at a low cost to perform cell therapy. Lin et al. reported the Celution output from 6 patients as 2.95 105 ADRCs per mL of lipoaspirate, with a mean viability of 86.6% [5]. Furthermore, clinical trials of free fat grafting using this device were performed in Europe [8]. The Celution800/CRS for free fat grafting is gaining recognition because the system provides clinical researchers with a real-time treatment setting that is cost-effective and safe. However, the optimal cell concentration and the effects of ADRCs on the characteristics of grafted fat after free fat grafting remain unclear. The purpose of this study was to investigate the optimal cell concentration of human ADRCs isolated by the Celution800/CRS and their effects on the characteristics of grafted fat after free fat grafting in a nude mouse fat transplantation model. Materials and methods The celution system and ADRC isolation The Celution800/CRS system was used in this study to extract ADRCs from human abdominal subcutaneous fat tissue (Figure 1). The system consisted of two parts: one for tissue washing and (...truncated)


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Natsuko Kakudo, Yoshihito Tanaka, Naoki Morimoto, Takeshi Ogawa, Satoshi Kushida, Tomoya Hara, Kenji Kusumoto. Adipose-derived regenerative cell (ADRC)-enriched fat grafting: optimal cell concentration and effects on grafted fat characteristics, Journal of Translational Medicine, 2013, pp. 254, 11, DOI: 10.1186/1479-5876-11-254