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.
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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)