Celution System Research Articles

Biological characterization of adipose‐derived regenerative cells used for the treatment of stress urinary incontinence

To assess the characteristics of adipose-derived regenerative cells, and provide supportive data explaining the mechanism of efficacy observed for the use of these cells in the treatment of stress urinary incontinence. Adipose tissues were harvested by abdominal liposuction from healthy donors and patients with stress urinary incontinence. Adipose-derived regenerative cells were isolated from tissues using the Celution system, and assessed for their characteristics and ability to differentiate into smooth muscle cells. Adipose-derived regenerative cells isolated by the Celution system developed into fibroblastic colonies. Flow cytometric analysis of adipose-derived stem cell markers showed that adipose-derived regenerative cells were positive for CD34 and CD44, and negative for CD31. Immunofluorescence staining after differentiation showed that colony-forming cells were positive for alpha-smooth muscle actin, calponin and desmin, which are smooth muscle cell markers. A cytokine release assay showed that adherent cells secreted cytokines associated with angiogenesis, including vascular endothelial growth factor-A, angiopoietin-2 and placental growth factor. Adipose-derived regenerative cells collected by the Celution system might have clonogenic capacity and an angiogenetic function. These properties might contribute to the mechanisms through which regenerative cell therapy by periurethral injection of autologous adipose-derived regenerative cells ameliorates stress urinary incontinence.

Regenerative treatment for male stress urinary incontinence by periurethral injection of adipose-derived regenerative cells: Outcome of the ADRESU study.

To report the outcome of the ADRESU study, a multicenter, single-arm, investigator-initiated clinical trial to confirm the efficacy and safety of regenerative treatment for male patients with stress urinary incontinence. The participants were male patients with mild-to-moderate stress urinary incontinence persisting for >1year after prostatectomy. Autologous adipose-derived regenerative cells were isolated using the Celution system from adipose tissue obtained by liposuction. Adipose-derived regenerative cells and mixture of adipose-derived regenerative cells with adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. The primary end-point was the proportion of patients with improvement of the urine leakage volume at 52weeks (or last visit within 52weeks). Improvement of leakage volume was defined as a decrease from baseline >50% by the 24-h pad test. A total of 10 secondary end-points were set. A total of 45 patients satisfying the eligibility criteria were enrolled. The primary end-point was met; the proportion of patients with improvement in leakage volume at 52weeks was 37.2% (95% confidence interval 23.0-53.3%). No serious adverse events with causal relationships to the adipose-derived regenerative cells were encountered. There was a progressive improvement in secondary end-points. In the King's Health Questionnaire, improvement of quality of life scores showed greater improvement in responders, as compared with non-responders. Findings from the ADRESU study suggest the efficacy and safety of regenerative treatment for male patients with mild-to-moderate stress urinary incontinence.

Combined Mastopexy and Augmentation with Autologous Fat Grafting: First Results with Lipopexy.

The treatment of breast ptosis and gland hypoplasia in a single surgery is a challenging procedure and the result is less predictable. In this surgery, the complications mainly concern the prosthesis, such as implant deflation, capsular contracture, palpability, or malposition. We, therefore, propose a different and new technique that avoids breast prosthesis, combining mastopexy and autologous augmentation with fat grafts. Combined mastopexy and autologous fat graft augmentation (lipopexy) was performed in women affected by breast ptosis and asymmetric breast or hypomastia. The breast lift technique was determined due to the ptosis level. The process of fat grafting was executed according to the PureGraft and, in some cases, to GID System, to Celution System or Carraway's techniques. Thirty-four patients affected by breast ptosis and hypomastia underwent lipopexy from January 2010 to May 2017. The mean volume of adipose tissue injected for each breast was 225.98 ml. After surgery, the patients were followed for an average of 22.8 months. A mild ptosis relapse with partial fat absorption was observed in 4 cases (11.76%) and the presence of oily cysts was diagnosed in 2 patients (5.88%). One severe complication was recorded (hematoma drainage). All the patients healed uneventfully in 2 weeks. This technique allows the surgeon to distribute the desired fat volume along the breasts, avoids implants, and displayed stable results. This treatment has been demonstrated not to interfere with follow-up breast imaging. We, therefore, consider lipopexy a valuable and safe alternative to mastopexy and mild to moderate breast volume augmentation.

Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell.

IntroductionAdipose tissue stromal cells contain a substantial number of mesenchymal stem cells. As such, their application to regeneration of miscellaneous impaired organs has attracted much attention.MethodsWe designed a clinical study to investigate freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell (ADRC) therapy for liver cirrhosis and conducted treatment in four cirrhotic patients. ADRCs were isolated from autologous subcutaneous adipose tissue obtained by the liposuction method, followed with use of the Celution system adipose tissue dissociation device. The primary endpoint is assessment of safety one month after treatment. We also characterized the obtained ADRCs.ResultsTwo patients had type C cirrhosis, one had nonalcoholic steatohepatitis-cirrhosis, and one had type B cirrhosis. No serious adverse events were observed during the 1-month study period after freshly isolated ADRC infusion. Serum albumin concentrations were maintained or improved during this period as well as during the succeeding follow-up of approximately 1 year in two patients and 6 months in another patient. Liver regeneration-related factors, namely hepatocyte growth factor and interleukin-6, were elevated 1 day after ADRC treatment in all patients. The obtained freshly isolated ADRCs were expanded in culture and found to express mesenchymal stem cell markers. Gene expression profile analysis of ADRCs was shown to involve inflammatory features, suggesting that characteristics of the obtained ADRCs were related to immunomodulatory biological effects.ConclusionThis clinical study treatment for liver cirrhosis using ADRCs was proven to be safely conductible, and can be further investigated in future for regeneration/repair of liver cirrhosis.

Breast Reconstruction with Enhanced Stromal Vascular Fraction Fat Grafting: What Is the Best Method?

Actually, there are 2 main methods to obtain stromal vascular fraction (SVF): enzymatic digestion and mechanical filtration; however, the available systems report heterogeneous and sometimes not univocal results. The aim of this study is to evaluate different procedures for SVF isolation and compare their clinical efficacy in the treatment of soft-tissue defects in plastic and reconstructive surgery. The authors evaluated Celution and Medikhan, enzymatic systems, and Fatstem and Mystem system, mechanical separation systems. Fifty patients affected by breast soft-tissue defects were treated in the Plastic and Reconstructive Surgery Department of Tor Vergata University of Rome. Four groups of 10 patients were managed with enhanced SVF fat grafts using cells obtained by Celution (Cytori Therapeutics, Inc., San Diego, Calif.), Medikhan (Medi-Khan Inc., West Hollywood, Calif.), Fatstem (Fatstem CORIOS Soc. Coop, San Giuliano Milanese, Italy), and Mystem (Mystem evo Bi-Medica, Treviolo, Italy) systems. A control group of 10 patients was treated with only centrifuged fat according to Coleman's technique. In enhanced SVF-treated patients treated with cells obtained by Celution system, we observed a 63% ± 6.2% maintenance of contour restoring after 1 year, compared with 39% ± 4.4% of control group. In patients treated with SVF obtained by Medikhan system, we observed a 39% ± 3.5% maintenance, whereas enhanced SVF with Fatstem and Mystem systems gave a 52% ± 4.6% and 43% ± 3.8% maintenance of contour restoring, respectively. SVF cell counting indicated that Celution and Fatstem were the most efficient systems to obtain SVF cells. Celution and Fatstem were the 2 best automatic systems to obtain SVF and to improve maintenance of fat volume and prevent the reabsorption.

Adipose-Derived Stromal Vascular Fraction Cells and Platelet-Rich Plasma

Actually, autologous fat grafts have many clinical applications in breast surgery, facial rejuvenation, buttock augmentation, and Romberg syndrome as well as a treatment of liposuction sequelae. The aim of this article was to describe the preparation and isolation procedures for stromal vascular fraction (SVF), the preparation of platelet-rich plasma (PRP), and the clinical application in the treatment of the scar on the face. Ten patients with burns sequelae (n = 6) and post-traumatic scars (n = 4) were treated with SVF-enhanced autologous fat grafts obtained by the Celution System. Another 10 patients with burns sequelae (n = 5) and post-traumatic scars (n = 5) were treated with fat grafting based on the Coleman technique mixed with 0.5 mL of PRP.To assess the effects of their treatment, the authors compared their results with those of a control group consisting of 10 patients treated with centrifuged fat. In the patients treated with SVF-enhanced autologous fat grafts, we observed a 63% maintenance of contour restoring after 1 year compared with only 39% of the control group (n = 10) treated with centrifuged fat graft (P < 0.0001). In the patients treated with fat grafting and PRP, we observed a 69% maintenance of contour restoring after 1 year compared with that of the control group (n = 10). Autologous fat grafting is a good method for the correction of scars on the face instead of the traditional scar surgical excision.

The Celution® System: Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed System.

Objective: To develop a closed, automated system that standardizes the processing of human adipose tissue to obtain and concentrate regenerative cells suitable for clinical treatment of thermal and radioactive burn wounds. Approach: A medical device was designed to automate processing of adipose tissue to obtain a clinical-grade cell output of stromal vascular cells that may be used immediately as a therapy for a number of conditions, including nonhealing wounds resulting from radiation damage. Results: The Celution® System reliably and reproducibly generated adipose-derived regenerative cells (ADRCs) from tissue collected manually and from three commercial power-assisted liposuction devices. The entire process of introducing tissue into the system, tissue washing and proteolytic digestion, isolation and concentration of the nonadipocyte nucleated cell fraction, and return to the patient as a wound therapeutic, can be achieved in approximately 1.5 h. An alternative approach that applies ultrasound energy in place of enzymatic digestion demonstrates extremely poor efficiency cell extraction. Innovation: The Celution System is the first medical device validated and approved by multiple international regulatory authorities to generate autologous stromal vascular cells from adipose tissue that can be used in a real-time bedside manner. Conclusion: Initial preclinical and clinical studies using ADRCs obtained using the automated tissue processing Celution device described herein validate a safe and effective manner to obtain a promising novel cell-based treatment for wound healing.

Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose‐derived regenerative cells: 1‐year outcomes in 11 patients

To assess the efficacy and safety of a novel cell therapy for male stress urinary incontinence consisting of periurethral injection of autologous adipose-derived regenerative cells, and to determine the 1-year outcomes. A total of 11 male patients with persistent stress urinary incontinence after prostate surgery were included in the study. The Celution system was used to isolate adipose-derived regenerative cells from abdominal adipose tissue obtained by liposuction. Subsequently, these regenerative cells, and a mixture of regenerative cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. The 1-year outcomes were assessed using a 24-h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography and magnetic resonance imaging. Stress urinary incontinence improved progressively in eight patients during the 1-year follow up, as determined by a 59.8% decrease in the leakage volume in the 24-h pad test, decreased frequency and amount of incontinence, and improved quality of life. One patient achieved total continence. The mean maximum urethral closing pressure and functional profile length increased from 35.5 to 44.7 cmH₂O, and from 20.4 to 26.0 mm, respectively. Magnetic resonance imaging showed the sustained presence of the injected adipose tissue, and enhanced ultrasonography showed a progressive increase in blood flow to the injected area in all patients. No significant adverse events were observed peri- or postoperatively. Periurethral injection of autologous adipose-derived regenerative cells might represent a safe and feasible treatment modality for male stress urinary incontinence.

Stem cell enrichment does not warrant a higher graft survival in lipofilling of the breast: A prospective comparative study

Stem cell enrichment is generally believed to be of crucial importance for success in lipofilling for cosmetic breast augmentation. No comparative clinical studies have been reported to support this. A total of 18 women underwent breast augmentation with water-assisted lipotransfer (WAL). In 10 of the cases, transferred lipoaspirate was enriched with stromal stem cells using the Celution(®) system (Cytori Therapeutics Inc., San Diego, Ca, USA). Magnetic resonance imaging (MRI)-based volumetric analysis was done preoperatively and 6 months after the procedure. To verify scientifically that stem cells were transplanted, samples of the transplanted tissues were processed in the laboratory to isolate the adipose stem cells (ASCs). MRI volumetry revealed a volume survival of the whole (watery) graft of mean 54% (SD 7) in the WAL only and of 50% (SD 10) in the WAL with stem cell-enrichment patients. As centrifugation of the WAL grafts demonstrated an average adipose tissue of 68%, the average volume survival of adipose tissue itself was 79% (SD 13) in the WAL only and 74% (SD 14) in the WAL with stem cell-enrichment patients. This difference (4.5%) was not statistically significant (independent samples t test, p = 0.330, 95% confidence interval of difference, 4.8, 13.9%). Breast augmentation by lipofilling using WAL alone is faster, cheaper, has a lower risk of contamination and offers at least an equal take rate. We do not see any advantage in stem cell enrichment by the Celution(®) system in cosmetic fat transplantation to the breast.

Therapy with autologous adipose-derived regenerative cells for the care of chronic ulcer of lower limbs in patients with peripheral arterial disease

BackgroundAn ulcer is a trophic lesion with loss of tissue that often has a multifactorial genesis. It typically diverges from the physiologic processes of regeneration because it rarely tends to heal spontaneously. In this study, we used purified adipose-derived stem and regenerative cells (ADRCs) extracted from autologous fat, for the care of chronic ulcers of the lower limbs of arteriopathic patients. The primary objective of this study was complete re-epithelization of chronic ulcers; the secondary objective was a decrease in diameter and depth. MethodsFrom January 2010 to January 2012, 20 patients with peripheral arterial disease, with an ankle-brachial index between 0.30–0.40, in the age range 60–70 y (14 men and six women), with chronic ulcers of the lower limb, were involved in the study. Only 10 arteriopathic patients (seven men and three women) with chronic ulcers of the lower limb were surgically treated. Using the Celution system, we isolated a solution of ADRCs in about 150 min. The isolated cells were injected through a 10-mL syringe into the edges of the ulcer, taking care to spread it in all directions. Using a small amount of Celution extract, we performed cell characterization by flow cytometry analysis and cell viability assay. ResultsWe monitored patients treated with ADRC or untreated at 4, 10, 20, 60, and 90 d. In all cases treated with ADRC, we found a reduction in both diameter and depth of the ulcer, which led to a decrease in pain associated with the ulcer process. In six of 10 cases there was complete healing of the ulcer. Characterization of the cells by FACS clearly showed that the ADRC cells contained adipose-derived stem cells. Viability assays demonstrated that partial or total closure of the ulcer was attributable exclusively to ADRC cells present in the Celution extract, and not to growth factors extracted during the process of purification of the Celution and injected together with the cells. ConclusionsFor the first time, the Celution method has been applied for the care of chronic ulcers in the lower extremity of patients with peripheral arterial disease. Our results demonstrate that the technique is feasible for autologous cell application and is not associated with adverse events. Moreover, the transplantation of autologous stem cells extracted with Celution may represent a valuable method for the treatment of chronic ulcers in lower limbs of arteriopathic patients.

Periurethral injection of autologous adipose‐derived regenerative cells for the treatment of male stress urinary incontinence: Report of three initial cases

To report a novel cell therapy using autologous adipose tissue-derived regenerative cells for male stress urinary incontinence caused by urethral sphincteric deficiency, and the outcomes in the initial cases undergoing periurethral injection of adipose tissue-derived regenerative cells. Three patients with moderate stress incontinence after radical prostatectomy and holmium laser enucleation of the prostate were enrolled. Adipose tissue-derived regenerative cells were isolated from the abdominal adipose tissue by using the Celution system. Subsequently, the isolated adipose tissue-derived regenerative cells, and a mixture of adipose tissue-derived regenerative cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Short-term outcomes during a 6-month follow up were assessed by a 24-h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography and magnetic resonance imaging. Urinary incontinence progressively improved after 2 weeks of injection up to 6 months in terms of decreased leakage volume, decreased frequency and amount of incontinence, and improved quality of life. Both maximum urethral closing pressure and functional profile length increased. Magnetic resonance imaging suggested a sustained presence of the injected adipose tissue. Enhanced ultrasonography showed a progressive increase in the blood flow to the injected area. No significant adverse events were observed peri- and postoperatively. These preliminary findings suggest that periurethral injection of the autologous adipose tissue-derived regenerative cells is a safe and feasible treatment modality for male stress urinary incontinence.

THIS ARTICLE HAS BEEN RETRACTED Periurethral injection of autologous adipose‐derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: Report of two initial cases

Objectives: To report a novel cell therapy using autologous adipose tissue‐derived stem cells (ADSC) for stress urinary incontinence caused by urethral sphincteric deficiency and the outcomes in two initial cases undergoing periurethral injection of stem cells for the treatment of urinary incontinence after radical prostatectomy.Methods: Two patients with moderate stress incontinence after radical prostatectomy were enrolled. After liposuction of 250 mL of adipose tissue from the abdomen, we isolated ADSC from this tissue by using the Celution system. Subsequently, the isolated ADSC and a mixture of stem cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Short‐term outcomes during a 12‐week follow‐up were assessed by a 24‐h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography, and magnetic resonance imaging.Results: Urinary incontinence progressively improved after 2 weeks of injection up to 12 weeks in terms of decreased leakage volume in a 24‐h pad test, decreased frequency and amount of incontinence, and improved quality of life as per the questionnaire. In urethral pressure profile, both maximum urethral closing pressure and functional profile length increased. Ultrasonography and magnetic resonance imaging showed sustained presence of the injected adipose tissue. Enhanced ultrasonography showed a progressive increase in the blood flow to the injected area. No significant adverse events were observed peri‐ and postoperatively.Conclusion: This preliminary study showed that periurethral injection of the autologous ADSC is a safe and feasible treatment modality for stress urinary incontinence.

Stem Cell Biotech: Seeking a Piece of the Action

Venture capital groups and big pharma have largely held back from investing in biotech companies focused on regenerative medicine. Will it take a clinical bull's eye to bring venture capitalists and big pharma into the cell therapy arena?

Characterization of adipose tissue-derived cells isolated with the Celution™ system

The therapeutic potential of using stem cells is tremendous. Mesenchymal stromal cells (MSC) have now been isolated in various tissues including bone marrow (BM), muscle, skin and adipose tissue. Among them, adipose tissue could be one of the most suitable cell sources for cell therapy, because of its easy accessibility, minimal morbidity and abundance of stem cells. The large numbers of stem cells in adipose tissue means that clinically relevant stem cell numbers could be extracted from the tissue, potentially eliminating the need for in vitro expansion. To utilize these characteristics of adipose tissue fully, Cytori Therapeutics Inc. has developed a closed system called Celution to isolate and concentrate stem cells and regenerative cells automatically from adipose tissue. Adipose tissue-derived cells were isolated using the Celution system. The output from the Celution was characterized using multicolor FACS analysis with CD31, CD34, CD45, CD90, CD105 and CD146. The multidifferentiation potential of the cells was analyzed using adipogenic and osteogenic media. Our results showed that cells from the Celution are composed of heterogeneous cell populations including adipose-derived stem cells (ASC) (CD31- CD34+ CD45- CD90+ CD105- CD146-), endothelial (progenitor) cells (CD31+ CD34+ CD45- CD90+ CD105- CD146+) and vascular smooth muscle cells (CD31- CD34+ CD45- CD90+ CD105- CD146+). We also confirmed the output contains cells able to differentiate into adipogenic and osteogenic phenotypes. Our results show that cells isolated with the Celution and manually are equivalent. Cells from adipose tissue can be processed by Celution within the time frame of a single surgical procedure. This system could provide a 'real-time' treatment setting that is cost-effective and safe.