J Transl Med. 2016 Jun 2;14(1):158. doi: 10.1186/s12967-016-0918-5.
Effects of the intramyocardial implantation of stromal vascular fraction in patients with chronic ischemic cardiomyopathy.
1US Stem Cell, Inc, Sunrise, FL, USA.
2Regenerative Medicine Institute, Tijuana, Mexico.
3Consultant Regenerative Medicine, Mother Cell Spinal Injury and Stem Cell Research, Anupam Hospital, Rudrapur, Uttarakhand, 263153, India.
Stromal vascular fraction (SVF) can easily be obtained from a mini-lipoaspirate procedure of fat tissue. The SVF contains a mixture of cells including ADSCs and growth factors and has been depleted of the adipocyte (fat cell) population. We evaluated the safety and efficacy of administering SVF intra-myocardially into patients with chronic ischemic cardiomyopathy.
A total of 28 patients underwent a local tumescent liposuction procedure to remove approximately 60 ml of fat tissue. The fat was separated to isolate the SVF and the cells were delivered into the akinetic myocardial scar region using a transendocardial delivery system (MyoCath(®)) in patients who had experienced a previous myocardial infarct. The subjects were then monitored for adverse events, ejection fraction via echocardiogram and six-minute walk test (6MWT) over a period of 6 months.
The average EF was 29 % at baseline and significantly increased to 35 % at both 3 and 6 months. Patients walked an average of 349 m at baseline and demonstrated a statistically significant improvement at 3 and 6 months’ post treatment of more than 80 m.
Overall, patients were pleased with the treatment results. More importantly, the procedure demonstrated a strong safety profile with no severe adverse events or complications linked to the therapy. Trial registration NCT01502514 Name of registry: http://www.clinicaltrials.gov URL: https://www.clinicaltrials.gov/ct2/show/NCT01502514?term=adipose+cells+heart&rank=4 Date of registration: December 27, 2011 Date of enrollment: January 2012.
Adipose derived stromal/stem cells (ADSCs); Adipose tissue; Cell therapy; Connective tissue; Ischemic cardiomyopathy; Stem cells; Stromal vascular fraction (SVF)
Am Heart J. 2014 Jul;168(1):88-95.e2. doi: 10.1016/j.ahj.2014.03.022. Epub 2014 Apr 5.
Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: The PRECISE Trial.
Perin EC1, Sanz-Ruiz R2, Sánchez PL2, Lasso J3, Pérez-Cano R3, Alonso-Farto JC4, Pérez-David E2, Fernández-Santos ME5, Serruys PW6, Duckers HJ6,Kastrup J7, Chamuleau S8, Zheng Y1, Silva GV1, Willerson JT1, Fernández-Avilés F9.
1Stem Cell Center, Texas Heart Institute, Houston, TX.
2Cardiology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
3Plastic Surgery Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
4Nuclear Medicine Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
5Cell Production Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
6Department of Interventional Cardiology, Thoraxcenter, Rotterdam, Utrecht, The Netherlands.
7Cardiology Department, Rigshospitalet University Hospital, Copenhagen, Denmark.
8Cardiology Department, University of Utrecht Medical Center, Utrecht, The Netherlands.
9Cardiology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
AIMS: Adipose-derived regenerative cells (ADRCs) can be isolated from liposuction aspirates and prepared as fresh cells for immediate administration in cell therapy. We performed the first randomized, placebo-controlled, double-blind trial to examine the safety and feasibility of the transendocardial injections of ADRCs in no-option patients with ischemic cardiomyopathy.
METHODS AND RESULTS: Procedural, postoperative, and follow-up safety end points were monitored up to 36 months. After baseline measurements, efficacy was assessed by echocardiography and single-photon emission computed tomography (6, 12, and 18 months), metabolic equivalents and maximal oxygen consumption (MVO2) (6 and 18 months), and cardiac magnetic resonance imaging (6 months). We enrolled 21 ADRC-treated and 6 control patients. Liposuction was well tolerated, ADRCs were successfully prepared, and transendocardial injections were feasible in all patients. No malignant arrhythmias were seen. Adverse events were similar between groups. Metabolic equivalents and MVO2 values were preserved over time in ADRC-treated patients but declined significantly in the control group. The difference in the change in MVO2 from baseline to 6 and 18 months was significantly better in ADRC-treated patients compared with controls. The ADRC-treated patients showed significant improvements in total left ventricular mass by magnetic resonance imaging and wall motion score index. Single-photon emission computed tomography results suggested a reduction in inducible ischemia in ADRC-treated patients up to 18 months.
CONCLUSION: Isolation and transendocardial injection of autologous ADRCs in no-option patients were safe and feasible. Our results suggest that ADRCs may preserve ventricular function, myocardial perfusion, and exercise capacity in these patients.
Ann Thorac Cardiovasc Surg. 2014;20(5):398-406. Epub 2014 Feb 4.
Study of adipose tissue-derived mesenchymal stem cells transplantation for rats with dilated cardiomyopathy.
1First Department of Cadres, First Hospital Affiliated to General Hospital of PLA, Beijing, China.
Increasing evidences indicated that adipose-derived mesenchymal stem cells (ADMSCs) can stay survive, then gradually proliferate and differentiate into myocardial cells after transplanted into damaged areas and improve function of heart.
In this article, ADMSCs were isolated from adipose tissue of Wistar rats and cultured. When treated with 5-azacytidine (5-aza), ADMSCs were differentiated into myocardial cells, then we implant these cells into myocardium of rats of DCM to observe cell population and differentiation and compare cardiac function and hemodynamics changes before and after transplantation.
The expression of Cardiac-specific markers indicated that ADMSCs which were isolated from adipose tissue of Wistar rats can differentiate into various cell types. Meanwhile, the treatment group displayed a higher level of LVESP, left ventricular intraventricular pressure (+dP/dt max), left ventricular intraventricular pressure (-dP/dt max) and left ventricular EF (%) than the control group. Altogether, these results indicate that heart systolic and diastolic function of rats of DCM was significantly improved meanwhile ventricular dilatation remodeling was inhibited after ADMSCs transplantation.
Therefore, this research provides an experimental basis for further clinical application of ADMSCs transplantation for the treatment of DCM and non-ischemic HF.