Three states of stromal cells–solid, liquid, and aerosol–and innovative delivery methods not previously reported

Article information

Arch Plast Surg. 2021;48(5):549-552

Publication date (electronic) : 2021 September 15

doi : https://doi.org/10.5999/aps.2021.00311

Hasim Eray Copcu

Department of Aesthetic Plastic Surgery, Mest Health Services, Izmir, Turkey

Correspondence: Hasim Eray Copcu Department of Aesthetic Plastic Surgery, Mest Health Services, Folkart Times Ofis 1. Blok, 602, 296 sok. No:8 Bornova, Izmir 35100, Turkey Tel: +90-232-4646378 Fax: +90-532-2434342 E-mail: ecopcu@gmail.com

This article was presented at PRS Korea 2020 on November 13, 2020.

Received 2021 February 8; Revised 2021 May 13; Accepted 2021 May 17.

Abstract

INTRODUCTION

Stromal cells obtained mechanically from adipose tissue have many advantages over those extracted with enzymatic methods. Beyond being faster, easier, and cheaper, the lack of restrictive regulations imposed by organizations has contributed to increasing interest in developing new methods and devices in this regard [1]. The goal of collecting stromal cells mechanically is to obtain “nanofat”–a semi-solid product in the form of emulsified fat–but the “stromal cell cocktail” obtained as the final product of the standard enzymatic method, called the stromal vascular fraction (SVF), is in liquid form. Although variations of nanofat are defined with different terms, such as cell aggregate or SVF gel, they are generally solid products in a very thin fat format. Today, nanofat, the “veteran” of mechanical methods, is applied clinically for many different indications, and with such a wide range of applications, there is a need for an end product available in various physical forms [2,3]. Copcu and Oztan defined a new technique and achieved high viability and cell count in stromal cell recovery by separating the bonds between parenchymal and stromal cells mechanically instead of with enzymes, using especially sharp blades [1]. Adinizing is the name given to cutting fat tissue using ultra-sharp blades. Copcu and Oztan [1] obtained the stromal cell with high viability and cell number from the adipose tissue mechanically with the adinizing process and named this process MEST (mechanical stromal-cell transfer). These authors, with the indication-based protocols (IPs) they defined, ensured that the final product stromal cells were in the desired physical structure in liquid or solid form (Table 1). The stromal cell can be obtained in liquid form when the condensed fat tissue is mixed with saline or similar liquid before adinizing (pre-adinizing) and then cut with ultra-sharp blades. Since the SVF term belongs to the final product in liquid form obtained with enzymatic products, and extracellular matrix and stromal cells are protected in mechanical methods, they call it total stromal cells (TOST) [4]. Stromal cells are generally applied to target tissue at the time of injection. However, this use is in the form of an emulsified fat graft. Different from all these, Verpaele et al. [5] presented the application of nanofat to the skin by needling as a new application technique. The stromal cell preparation used was in a semi-solid, emulsified fat state. In the same publication, they also reported the application of a “nanofat cream” they produced after the process [5]. Similarly, Cohen et al. [6] applied millifat as biocream. In this study, three application methods are presented as new innovative approaches (Fig. 1), all of which are obtained mechanically and have not been reported before.

Table 1.

Summary of IPs, adinizing: cutting of the fat tissue with ultra-sharp blades, TOST

Fig. 1.

View of three states of stromal cells by mechanical extraction technique. (A) A photograph of the hydra-roller with TOST (liquid state). (B) View of the nebulizer collection unit with TOST (aerosol state). (C) A photograph of the TOST gel with plasma (solid state). TOST, total stromal cells.

IDEA

This study is a pre-clinic study showing three new and different application possibilities of stromal cells, and 21 separate trials were conducted according to the standards of good medical practice (ICH-E6) and the principles of the Declaration of Helsinki. All patients were provided detailed information preoperatively and gave written consent for all surgical procedures, anesthesia, intraoperative video recording, and photography. In addition, a written consent form was obtained from the patients stating that they willingly donated their adipose tissue for laboratory analysis. In this study, a patented CE (European Conformity) marking and ISO 13485 certified blade system was used, and rules of minimal manipulation were followed. No enzymes and similar chemicals were used, and the structure of the fat tissue was not altered.

In this study, stromal cells were obtained from adipose tissue in liquid or solid form in accordance with the technique called MEST described by Copcu and Oztan [1]. Under local anesthesia, 5/10 mL of adipose tissue according to the IPs was harvested from abdominal area with 3-mm diameter 4-hole cannula and then centrifuged at a speed of 500 g for 2 minutes and condensed fat was obtained by discarding tumescent fluid and blood elements. Then, adinizing process was performed with 2,400 μm, 1,200 μm, 600 μm, and finally 400 μm diameter ultrasharp blades (Adinizer; BSL-rest, Seoul, Korea), with 25 back and forth movements between two injectors. Finally, stromal cells were obtained by centrifugation at 1,200 g for 5 minutes.

Results

Each new delivery method was tested in 20 different cases and the average of the obtained results is presented in Table 2.

Table 2.

Effectiveness of TOSTs in different physical states

DISCUSSION

This innovative delivery method may be a very important approach. Copcu [7,8] stated that stromal cells could potentially be used in the treatment of coronavirus disease 2019 (COVID-19) and similar conditions. It has been reported that it can potentially be used in prevention, treatment, and sequelae repair. Its use in aerosol form with the nebulizer may create an alternative route for stromal cell administration in future COVID-19-like situations. However, further studies are required in this regard.

In this study, as innovations and ideas, stromal cells obtained mechanically from adipose tissue are presented in three forms that have not been previously reported. Their clinical significance and results should be evaluated in further studies. The possibility of applying stromal cells as solids could create an important alternative for dermis, such as hyaluronic acid. Being autogenous will prevent complications due to filling and provide tissue regeneration as well as filling in the stromal cells it contains. Simultaneous application of liquid stromal cells with hydro-roller can provide the desired results with both the physical effects and healing and the restorative effects of stromal cells, which will provide a synergistic effect [9]. Although Zimmerlin et al. [10] described intra-tracheal route of stromal cells combining with fibrin, the application of fresh mechanical stromal cells in the form of aerosol is a promising new approach.

Supplementary Material

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