Recently the question was raised whether anybody ever had encountered a negative scientific -peer reviewed- study involving Cytori´s processing device Celution, which had been-as written- unfavorable i.e. negative in its conclusions.
In order to be able to give a substantiated answer to this question, one really has to know first which scientific- peer reviewed- papers do exist on the subject, so since I have been rather involved with the art of interrogating databases, I did so with the pretty substantial- and complete PubMed database. Off late the DB has been returning more and more publications from Private Investigator clinics and it is very likely that the funnel of these investigations has been growing and growing and beats the quality of Cytori´s past own investigations by many many miles. But also, that funnel will also "spit out" more results in the near future- Cugat -as an example- is expected any day now with his ACL results.
So- it starts to be interesting to put FOCUS on what is being issued in the various scientific journals of the globe, in order to be able to glimps at Cytori´s platform future.
In order to do so- glimpsing on what is ongoing- I did a query on the PubMed database with the search parameter " Celution" at present- end July 2016- 19 positives are returned, which you will find listed below. Going forward the list will stop at 20....but will start with the latest published article and will delete the eldest.
To answer that question- yes, there is one. A study from Finland I believe, where the investigators used "water assisted liposuction" for their scientific comparison with manual extraction of supercharged fat in reconstruction. All I recall is, that I inquired in Finland, why the hell they did this study with this lipo device. The PI answered me that he did the study, since he was a friend of Adam Katz- Co-founder of StemSource. For insiders, this is all explanatory...
The Query Results
Adipose-Derived Regenerative Cell Injection Therapy for Postprostatectomy Incontinence: A Phase I Clinical Study.
Yonsei Med J. 2016 Sep;57(5):1152-8
Authors: Choi JY, Kim TH, Yang JD, Suh JS, Kwon TG
PURPOSE: We report our initial experience with transurethral injection of autologous adipose-derived regenerative cells (ADRCs) for the treatment of urinary incontinence after radical prostatectomy.
MATERIALS AND METHODS: After providing written informed consent, six men with persistent urinary incontinence after radical prostatectomy were enrolled in the study. Under general anesthesia, about 50 mL of adipose tissue was obtained from the patients by liposuction. ADRCs were obtained by separation with centrifugation using the Celution cell-processing device. A mixture of ADRCs and adipose tissue were transurethrally injected into the submucosal space of the membranous urethra. Functional and anatomical improvement was assessed using a 24-h pad test, validated patient questionnaire, urethral pressure profile, and magnetic resonance imaging (MRI) during 12-week follow-up.
RESULTS: Urine leakage volume was improved with time in all patients in the 24-h pad test, with the exemption of temporal deterioration at the first 2 weeks post-injection in 2 patients. Subjective symptoms and quality of life assessed on the basis of questionnaire results showed similar improvement. The mean maximum urethral closing pressure increased from 44.0 to 63.5 cm H₂O at 12 weeks after injection. MRI showed an increase in functional urethral length (from 6.1 to 8.3 mm) between the lower rim of the pubic bone and the bladder neck. Adverse events, such as pelvic pain, inflammation, or de novo urgency, were not observed in any case during follow-up.
CONCLUSION: This study demonstrated that transurethral injection of autologous ADRCs can be a safe and effective treatment modality for postprostatectomy incontinence.
PMID: 27401646 [PubMed - in process]
The Athena Trials: Autologous Adipose-Derived Regenerative Cells (ADRCs) for Refractory Chronic Myocardial Ischemia with Left Ventricular Dysfunction.
Catheter Cardiovasc Interv. 2016 May 5;
Authors: Henry TD, Pepine C, Lambert C, Traverse JH, Schatz R, Costa M, Povsic TJ, Anderson RD, Kesten S, Perin EC
OBJECTIVE: To assess safety and feasibility of autologous Adipose-Derived Regenerative Cells(ADRCs), for treatment of chronic ischemic cardiomyopathy patients.
BACKGROUND: Preclinical and early clinical trials suggest ADRCs have excellent potential for ischemic conditions.
METHODS: The Athena program consisted of 2 parallel, prospective, randomized (2:1, active: placebo), double-blind trials assessing intramyocardial (IM) ADRC delivery [40-million, n=28 (ATHENA) and 80-million (ATHENA II) cells, n=3]). Patients with an EF ≥20% but ≤45%, multi-vessel coronary artery disease (CAD) not amenable to revascularization, inducible ischemia, and symptoms of either angina (CCS II-IV) or heart failure (NYHA Class II-III) on maximal medical therapy were enrolled. All patients underwent fat harvest procedure (≤450 mL adipose), on-site cell processing (Celution® System, Cytori Therapeutics), electromechanical mapping and IM delivery of ADRCs or placebo.
RESULTS: Enrollment was terminated prematurely due to non-ADRC-related adverse events and subsequent prolonged enrollment time. Thirty-one patients (17-ADRCs, 14-placebo) mean age 65±8 yrs, baseline LVEF(%) 31.1±8.7(ADRC), 31.8±7.7(placebo) were enrolled. Change in V02 max favored ADRCs (+45.4±222 vs. -9.5±137mL/sec) but there was no difference in left ventricular function or volumes. At 12-months, heart failure hospitalizations occurred in 2/17 (11.7%) [ADRC] and 3/14 (21.4%) [placebo]. Differences in NYHA and CCS classes favored ADRCs at 12-months with significant improvement in MLHFQ (-21.6 + 13.9 vs. -5.5 + 23.8, p=0.038).
CONCLUSIONS: A small volume fat harvest, automated local processing, and IM delivery of autologous ADRCs is feasible with suggestion of benefit in "no option" CAD patients. Although the sample size is limited, the findings support feasibility and scalability for treatment of ischemic cardiomyopathy with ADRCs. This article is protected by copyright. All rights reserved.
PMID: 27148802 [PubMed - as supplied by publisher]
A clinical trial of autologous adipose-derived regenerative cell transplantation for a postoperative enterocutaneous fistula.
Surg Today. 2016 Jul;46(7):835-42
Authors: Mizushima T, Takahashi H, Takeyama H, Naito A, Haraguchi N, Uemura M, Nishimura J, Hata T, Takemasa I, Yamamoto H, Doki Y, Mori M
PURPOSE: Adipose-derived stem cell (ADSC) transplantation is expected to be a minimally invasive, but effective, treatment for postoperative enterocutaneous fistulas associated with poor blood flow and chronic inflammation. The aim of this study was to assess the safety and efficacy of a novel ADSC therapy for this condition.
METHODS: We conducted an open-label, single-arm exploratory phase I study to assess the safety and efficacy of a novel ADSC therapy. Using the Celution system, we isolated adipose-derived regenerative cells (ADRCs) containing abundant ADSCs from liposuction-obtained gluteal adipose tissue. A mixture of ADRCs and fibrin glue was subsequently transplanted into the fistula, and ADRCs were percutaneously and endoscopically injected around the fistula. We evaluated the safety and feasibility of ADRC transplantation and fistula closure in six patients (UMIN000007316).
RESULTS: ADRC transplantation was completed in all patients. The fistula closure rates were 83.3 % at 4 and 12 weeks and 100 % at 24 weeks. All patients had grade 1 pain and subcutaneous hemorrhage at the liposuction sites, but no serious adverse events related to this procedure were observed.
CONCLUSIONS: Transplantation of autologous ADRCs is safe, feasible and advantageous, as it can secure a sufficient cell count without culture or multiple passages, and will likely be effective for a postoperative enterocutaneous fistula.
PMID: 26342817 [PubMed - in process]
Breast Reconstruction with Enhanced Stromal Vascular Fraction Fat Grafting: What Is the Best Method?
Plast Reconstr Surg Glob Open. 2015 Jun;3(6):e406
Authors: Gentile P, Scioli MG, Orlandi A, Cervelli V
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Celution and Fatstem were the 2 best automatic systems to obtain SVF and to improve maintenance of fat volume and prevent the reabsorption.
PMID: 26180707 [PubMed]
Adipose Tissue-Derived Regenerative Cell-Enhanced Lipofilling for Treatment of Cryptoglandular Fistulae-in-Ano: The ALFA Technique.
Surg Innov. 2015 Dec;22(6):593-600
Authors: Borowski DW, Gill TS, Agarwal AK, Tabaqchali MA, Garg DK, Bhaskar P
BACKGROUND: The treatment of complex fistulae-in-ano is challenging and often includes a number of operations due to high rates of recurrence. Recently, techniques using in vitro expanded adipose tissue-derived stem cells have been described. We describe a novel treatment for cryptoglandular fistulae used in 7 patients, using a combination of surgical closure of the internal opening and real-time autologous adipose tissue-derived regenerative cells (ADRC)-enhanced lipofilling, without need for in vitro expansion.
METHODS: Following exclusion of active perianal sepsis, patients underwent a standard tumescent liposuction procedure, harvesting ~300 to 400 mL of raw lipoaspirate. The lipoaspirate was prepared in real time, using the Celution 800/CRS system to obtain the stromal vascular fraction containing ADRCs. After excision of the fistula tract and closure of the internal orifice, fresh ADRC-enhanced lipoaspirate was injected into and around the fistula tract.
RESULTS: At 6-months' follow-up, 5 of 7 (71.4%) patients showed clinical signs of fistula closure; one of these patients had a recurrence at 10 months due to sepsis. The remaining 4 patients (57.1%) all had complete fistula closure at a median of 46 months' follow-up. There were no adverse events associated with the technique, and no new incontinence.
CONCLUSION: Treatment of cryptoglandular fistulae-in-ano with ADRC-enhanced lipofilling appears feasible and safe, and may add to the range of procedures that can be used to treat this difficult problem.
PMID: 25710946 [PubMed - in process]
Devices for stem cell isolation and delivery: current need for drug discovery and cell therapy.
Expert Rev Med Devices. 2015 May;12(3):353-64
Authors: Reinhardt M, Bader A, Giri S
Isolation and purification of stem cells and their delivery into diseased or aged tissues or organs need special devices for proper transplantation of stem cells in order to achieve high cell retention at transplant site for repair or regeneration of tissues and organs. The clinical and preclinical importance of special devices such as Celution System, Isolex cell separation device, magnetic surface-enhanced Raman spectroscopic dots, microfluidic devices, immunomagnetic cell separation for stem cell separation and isolation are the main focus in this paper. Further, devices like trans-coronary delivery, trans-endocardial delivery, intracoronary delivery devices for stem cell application to the heart are described. Devices for stem cell application to the brain, the spinal cord and other tissues are also explained. We highlighted scaffolds with incorporated stem cells and other encapsulation devices used to transplant stem cells. Current needs of devices for stem cells isolation, purification and delivery for drug discovery and cell therapy are discussed.
PMID: 25540074 [PubMed - indexed for MEDLINE]
The Celution(®) System: Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed System.
Adv Wound Care (New Rochelle). 2014 Jan 1;3(1):38-45
Authors: Fraser JK, Hicok KC, Shanahan R, Zhu M, Miller S, Arm DM
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.
PMID: 24761343 [PubMed - as supplied by publisher]
Adipose-derived stromal vascular fraction cells and platelet-rich plasma: basic and clinical evaluation for cell-based therapies in patients with scars on the face.
J Craniofac Surg. 2014 Jan;25(1):267-72
Authors: Gentile P, De Angelis B, Pasin M, Cervelli G, Curcio CB, Floris M, Di Pasquali C, Bocchini I, Balzani A, Nicoli F, Insalaco C, Tati E, Lucarini L, Palla L, Pascali M, De Logu P, Di Segni C, Bottini DJ, Cervelli V
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: Autologous fat grafting is a good method for the correction of scars on the face instead of the traditional scar surgical excision.
PMID: 24406591 [PubMed - indexed for MEDLINE]
Adipose stromal vascular fraction isolation: a head-to-head comparison of four commercial cell separation systems.
Plast Reconstr Surg. 2013 Dec;132(6):932e-9e
Authors: Aronowitz JA, Ellenhorn JD
BACKGROUND: Supplementation of fat grafts with stromal vascular fraction cells is an emerging technique used to improve graft reliability. A variety of systems for isolating stromal vascular fraction cells are commercially available. The lack of performance data obtained operating the systems in a standardized environment prevents objective assessment of performance. This prospective, blinded study compared performance of four commercially available stromal vascular fraction isolation systems when operated in a clinical outpatient surgery environment.
METHODS: Four different systems were compared: (1) PNC's Multi Station, (2) CHA Biotech Cha-Station, (3) Cytori Celution 800/CRS System, and (4) Medi-Khan's Lipokit with MaxStem. Identical lipoaspirate samples from five separate volunteer donors were used to evaluate system process time, viable cell yield, composition, residual enzyme, and operating costs.
RESULTS: The mean processing time ranged from 88 to 115 minutes. The highest mean number of viable nucleated cells was obtained using the Celution System (2.41 × 10 cells/g) followed by the Multi Station (1.07 × 10 cells/g). Lipokit and Cha-Station systems yielded nearly a log fewer nucleated cells (0.35 × 10 cells/g and 0.05 × 10 cells/g, respectively). The Celution System also yielded significantly more endothelial cells, CD34/CD31 cells, and adipose-derived stem cells (colony-forming unit-fibroblast). Residual enzyme levels observed with the Multi Station, Cha-Station, and Lipokit, respectively, averaged 5.1-, 13.0-, and 57-fold higher than that observed with the Celution System.
CONCLUSIONS: Although all systems generated measurable amounts of stromal vascular fraction, significant variability exists in the number, identity, and safety profiles of recovered viable cells. Side-by-side clinical trials will be required to establish the relevance of these differences.
PMID: 24281640 [PubMed - indexed for MEDLINE]
Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose-derived regenerative cells: 1-year outcomes in 11 patients.
Int J Urol. 2014 Mar;21(3):294-300
Authors: Gotoh M, Yamamoto T, Kato M, Majima T, Toriyama K, Kamei Y, Matsukawa Y, Hirakawa A, Funahashi Y
OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: Periurethral injection of autologous adipose-derived regenerative cells might represent a safe and feasible treatment modality for male stress urinary incontinence.
PMID: 24033774 [PubMed - indexed for MEDLINE]
Stem cell enrichment does not warrant a higher graft survival in lipofilling of the breast: a prospective comparative study.
J Plast Reconstr Aesthet Surg. 2013 Nov;66(11):1494-503
Authors: Peltoniemi HH, Salmi A, Miettinen S, Mannerström B, Saariniemi K, Mikkonen R, Kuokkanen H, Herold C
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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%).
CONCLUSIONS: 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.
PMID: 23845909 [PubMed - indexed for MEDLINE]
Therapy with autologous adipose-derived regenerative cells for the care of chronic ulcer of lower limbs in patients with peripheral arterial disease.
J Surg Res. 2013 Nov;185(1):36-44
Authors: Marino G, Moraci M, Armenia E, Orabona C, Sergio R, De Sena G, Capuozzo V, Barbarisi M, Rosso F, Giordano G, Iovino F, Barbarisi A
BACKGROUND: An 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.
METHODS: From 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.
RESULTS: We 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.
CONCLUSIONS: For 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.
PMID: 23773718 [PubMed - indexed for MEDLINE]
Autologous adipose-tissue derived regenerative cells for the treatment of complex cryptoglandular fistula-in-ano: a report of three cases.
BMJ Case Rep. 2012;2012
Authors: Borowski DW, Gill TS, Agarwal AK, Bhaskar P
The treatment of complex fistulae-in-ano is challenging and often includes a number of operations due to high rates of recurrence. We report the successful treatment of three consecutive patients with long-standing cryptoglandular fistula-in-ano with a novel combination of mucosal advancement flap and adipose-tissue derived regenerative cells (ADRCs) from the stromal vascular fraction (SVF) obtained from a simple lipoaspiration procedure, using Celution technology. There was no operative morbidity; one patient who had a colostomy for faecal diversion has since undergone restoration of bowel continuity. All thee fistulae remain healed at 2-3-year follow-up. Lipofilling of cryptoglandular fistulae-in-ano with ADRC-enhanced lipofilling appears feasible and safe, and may add to the range of procedures that can be used to treat this difficult problem.
PMID: 23144344 [PubMed - indexed for MEDLINE]
Periurethral injection of autologous adipose-derived regenerative cells for the treatment of male stress urinary incontinence: Report of three initial cases.
Int J Urol. 2012 Jul;19(7):652-9
Authors: Yamamoto T, Gotoh M, Kato M, Majima T, Toriyama K, Kamei Y, Iwaguro H, Matsukawa Y, Funahashi Y
OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
PMID: 22435469 [PubMed - indexed for MEDLINE]
Autologous cell-enriched fat grafting for breast augmentation.
Aesthetic Plast Surg. 2011 Dec;35(6):1022-30
Authors: Kamakura T, Ito K
Autologous fat grafting for breast augmentation has faced some historical hurdles. However, in recent years it has been gaining acceptance from the medical community. This prospective, nonrandomized open-label study of 20 Japanese women supports the use of autologous fat grafting in breast augmentation and explores enhancement of fat graft tissue with autologous adipose-derived regenerative cells (ADRCs). After adipose harvesting using syringe liposuction, the tissue is processed in the Celution 800 System(®), which washes the graft and isolates ADRCs. The average cells per gram of harvested adipose tissue was 3.42 × 10(5), and the mean cell viability measured using an automated cell counting system before graft delivery was 85.3%. All patients demonstrated improvement in circumferential breast measurement (BRM) from their baseline state, and breast measurements were stable by 3 months after surgery. The mean BRM 9 months after surgery had increased 3.3 cm from preoperative measurements. Through 9 months, overall physician satisfaction was 69% and patient satisfaction was 75%. No serious or unexpected adverse events were reported, and the procedure was safe and well tolerated in all patients. Postoperative cyst formation was seen in two patients. These prospective results demonstrate that ADRC-enriched fat grafts processed with a closed automated system maintain high cell viability and that the procedure is safe and effective, with all patients showing improvement after a single treatment.
PMID: 21533662 [PubMed - indexed for MEDLINE]
Automated isolation and processing of adipose-derived stem and regenerative cells.
Methods Mol Biol. 2011;702:87-105
Authors: Hicok KC, Hedrick MH
The popularity of nonhematopoietic, adult tissue-derived stem and progenitor cells for use as a cellular research tool, and ultimately as a clinical therapeutic, has increased exponentially over the past decade. Almost all adult-derived stem/progenitor cells (autologous and allogeneic), with one exception, require at least some ex vivo expansion or further manipulation prior to use to satisfy efficacy and safety requirements for preclinical or clinical use. The principal reason is the relatively low frequency of these therapeutically valuable cells within any given adult tissue, except for adipose tissue, which has been shown to have at least two log greater concentrations of these progenitor cells. Therefore, use of autologous adipose-derived cells as both a research tool and cell therapeutic is feasible and has been shown to be both safe and efficacious in preclinical and clinical models of injury and disease. The development and utilization of automated processes and instrumentation such as Cytori Therapeutics' Celution® System to reduce variability and increase quality of the recovered cells is requisite for clinical use and preferred by basic researchers. Here, use of an automated, closed processing platform for isolation and concentration of adipose-derived stem and regenerative cells is described, including a profile of the isolated cells immediately prior to use, and commonly used methods to quantify and qualitatively assess the recovered cells.
PMID: 21082397 [PubMed - indexed for MEDLINE]
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.
Int J Urol. 2010 Jan;17(1):75-82
Authors: Yamamoto T, Gotoh M, Hattori R, Toriyama K, Kamei Y, Iwaguro H, Matsukawa Y, Funahashi Y
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.
PMID: 20002225 [PubMed - indexed for MEDLINE]
Characterization of adipose tissue-derived cells isolated with the Celution system.
Authors: Lin K, Matsubara Y, Masuda Y, Togashi K, Ohno T, Tamura T, Toyoshima Y, Sugimachi K, Toyoda M, Marc H, Douglas A
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
DISCUSSION: 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.
PMID: 18574774 [PubMed - indexed for MEDLINE]
The Bedside Celution system for isolation of adipose derived regenerative cells.
EuroIntervention. 2006 Nov;2(3):395-8
Authors: Duckers HJ, Pinkernell K, Milstein AM, Hedrick MH
PMID: 19755319 [PubMed]