Congestive Heart Failure (CHF) and Cardiomyopathy
 

     Congestive heart failure (CHF) is responsible for many one million hospitalizations in the U.S. and is considered the main cause or contributor to 53,000 deaths each year in the United States. CHF is associated with cardiomyopathy. Cardiomyopathy (deterioration in heart muscles) is commonly caused by coronary vessel disease but can also be due to infection and other causes. In this condition, the heart loses its ability to pump blood efficiently.

     Cell therapy potentially offers an important solution for CHF and cardiomyopathy. During cardiac ischemia, millions of myocytes are lost resulting in loss of contractile function. One of the great goals of regenerative medicine is to engineer methods of replacing these cells. Bone marrow derived mesenchymal stem cells and now recently adipose derived mesenchymal stem cells appear to be playing an important role in this regeneration. There is also a growing body of data supporting the use of engineered biologics such as selected cell populations, organic scaffolds, and modified (differentiated or de-differentiated) stem cells to regenerate damaged myocardium. It is unknown whether the cost of engineered biologics over harvested stem cells is justified until long term studies are available. The results of clinical trials of the use of adult mesenchymal stem cells to treat cardiac disease have demonstrated safety and most have shown positive clinical results. Mesenchymal stem cells have been deployed intravenously, injected the myocardium, and placed in the coronary arteries and it is still unclear if one delivery method is clearly superior to another. It is also unclear which source of mesenchymal cells is optimal for cardiac regeneration but adipose derived cells appear to be highly effective in this area.

     Research has been ongoing around the world that exploits the anti-inflammatory and regenerative properties of adult stem cells to mitigate heart failure. We are investigating the effects of SVF (rich in mesenchymal stem cells and growth factors) on CHF. We use a protocol designed by our interventional cardiologist that includes intravenous deployment. The CSCTC deployment protocol is performed under local anesthesia and is all done as an outpatient at the time of SVF harvesting and procurement. The entire cellular surgical procedure takes approximately 3 hours.

 
CANDIDATE APPLICATION
RESOURCES

Cell Surgical Network Study for Stromal Vascular Fraction Registered by ClinicalTrials.gov

Rancho Mirage, CA (PRWEB) October 14, 2013

Clinicaltrials.gov, a service of the U.S. National Institutes of Health has registered on their public site an IRB approved safety study from the Cell Surgical Network, Inc.. This study is available for patients with various degenerative and inflammatory conditions to undergo Stromal Vascular Fraction deployment for the evaluation and for the advancement of future stem cell therapy procedures. Stromal Vascular Fraction is rich in autologous adipose derived stem cells and growth factors.

Stromal Vascular Fraction (SVF) is obtained by lipo-harvesting, procurement, and lipo-transfer as a same day operative procedure to provide therapy to patients with various degenerative and inflammatory diseases. Patients must be 16 years or older, male or female and have a degenerative disease or inflammatory disease that meets criteria for treatment under the IRB which includes: Arthritis, Auto-immune disease, COPD, Cardiomyopathy, Peyronies Disease, Interstitial Cystitis, Erectile Dysfunction, and Neurodegenerative disease such as Parkinson’s, ALS, Neuropathy. Patients must be healthy enough to tolerate a local anesthetic, must not have active cancer or infections.

Dr. Elliot Lander, and Dr. Mark Berman, founders of the Cell Surgical Network Inc. will conduct the study: “Ever since our inception, it’s been our goal to maintain transparency during our investigations. With a closed surgical procedure we can provide effective safety studies and evolve good empirical data that will allow us and others to ultimately refine our protocols,” says Dr. Berman.

The purpose of the safety study is to evaluate for any adverse effects that may be related to the administration and reception of autologous adipose derived stromal vascular fraction (SVF). Secondarily, the study monitors the results of subjective and objective findings as it applies to the non-blinded deployment of autologous SVF for various inflammatory and/or degenerative conditions including select orthopedic, neurologic, urologic and cardio-pulmonary conditions. SVF deployments include intra-venous, intra-articular, and soft tissue injections.

Outcome measures will include the number of participants with adverse events related to either SVF deployment or the lipo-harvesting procedure. Interested patients should contact the treatment center by phone: 800-231-0407 or via email: info(at)cellsurgicalnetwork(dot)com

About Cell Surgical Network:

The affiliates of the Cell Surgical Network (CSN) are devoted to advancing access and quality care in the area of adult stem cell regenerative medicine in order to help people suffering from a variety of inflammatory and degenerative conditions. The Cell Surgical Network was founded nearly two years after the formation of the California Stem Cell Treatment Center (founded in 2010). Affiliate members are generally made up of multi-state and international teams of multidisciplinary physicians in order to best assess and provide care for our patients. The Cell Surgical Network emphasizes quality and is highly committed to clinical research and the advancement of regenerative medicine.

 

The Athena trials: Autologous adipose-derived regenerative cells for refractory chronic myocardial ischemia with left ventricular dysfunction.


 Catheter Cardiovasc Interv. 2017 Feb 1;89(2):169-177. doi: 10.1002/ccd.26601. Epub 2016 Sep 23.

Authors: Henry TD, Pepine CJ, Lambert CR, Traverse JH, Schatz R, Costa M, Povsic TJ, David Anderson R, Willerson JT, Kesten S, Perin EC.

Abstract
 
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 two 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%, multivessel 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 years, 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 ± 137 mL/min) 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. © 2016 Wiley Periodicals, Inc.

 

Effects of the intramyocardial implantation of stromal vascular fraction in patients with chronic ischemic cardiomyopathy.
 


J Transl Med. 2016 Jun 2;14(1):158. doi: 10.1186/s12967-016-0918-5.

Authors: Comella K, Parcero J2, Bansal H, Perez J, Lopez J, Agrawal A, Ichim T.

 

Abstract
 
BACKGROUND: 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.

 

METHODS: 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.

 

RESULTS: 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.

 

CONCLUSIONS: 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.

 
 Stem cells in cardiovascular diseases: turning bad days into good ones.
 

Drug Discov Today. 2017 Aug 4. pii: S1359-6446(17)30016-8. doi: 10.1016/j.drudis.2017.07.012. [Epub ahead of print]

Oliveira MS, Saldanha-Araujo F, Goes AM, Costa FF, de Carvalho JL.

Abstract
 
During the past decade, several types of stem cells have been investigated as promising therapeutic agents for cardiovascular diseases (CVDs). Among them, mesenchymal stem cells (MSCs) were the most investigated stem cell population. Hundreds of clinical trials later, results remain disappointing and far from the revolutionary improvements expected for heart function. In the present review, we address strategies under investigation to boost MSC therapy for CVDs. Pluripotent stem cells (PSCs) are also intended to reach clinical applications for CVDs, but here we suggest that, in the short term, the major impact of PSCs in the cardiovascular field might be at the bench and not the bedside.

 
Cell therapy for heart disease after 15 years: Unmet expectations.


 Pharmacol Res. 2017 Feb 21. pii: S1043-6618(16)31000-3. doi: 10.1016/j.phrs.2017.02.015. [Epub ]

Authors: Nigro P, Bassetti B, Cavallotti L, Catto V, Carbucicchio C, Pompilio G.

Abstract
Over the past two decades cardiac cell therapy (CCT) has emerged as a promising new strategy to cure heart diseases at high unmet need. Thousands of patients have entered clinical trials for acute or chronic heart conditions testing different cell types, including autologous or allogeneic bone marrow (BM)-derived mononuclear or selected cells, BM- or adipose tissue-derived mesenchymal cells, or cardiac resident progenitors based on their potential ability to regenerate scarred or dysfunctional myocardium. Nowadays, the original enthusiasm surrounding the regenerative medicine field has been cushioned by a cumulative body of evidence indicating an inefficient or modest efficacy of CCT in improving cardiac function, along with the continued lack of indisputable proof for long-term prognostic benefit. In this review, we have firstly comprehensively outlined the positive and negative results of cell therapy studies in patients with acute myocardial infarction, refractory angina and chronic heart failure. Next, we have discussed cell therapy- and patient-related variables (e.g. cell intrinsic and extrinsic characteristics as well as criteria of patient selection and proposed methodologies) that might have dampened the efficacy of past cell therapy trials. Finally, we have addressed critical factors to be considered before embarking on further clinical trials.

 

Mesenchymal stromal cell therapy in ischemic heart disease.
 

 
Scand Cardiovasc J. 2016 Oct - Dec;50(5-6):293-299. Epub 2016 Sep 22.

Authors: Kastrup J, Mygind ND, Qayyum AA, Mathiasen AB, Haack-Sørensen M, Ekblond A.

Abstract
 
Although, treatment of ischemic heart disease (IHD) has improved considerably within the last decades, it is still the main cause of death worldwide. Despite maximum treatment, many IHD patients suffer from refractory angina and heart failure, which severely limits their daily lives. Moreover, IHD is very costly for the health care system. Therefore, new treatment options and strategies are being researched intensely. Stem cell therapy to improve myocardial perfusion and stimulate growth of new cardiomyocytes could be a new way to go. Nevertheless, the results from clinical studies have varied considerably, probably due to the use of many different cell lines obtained from different tissues and the different patient populations. The present review will focus on treatment with the mesenchymal stromal cell from bone marrow and adipose tissue in animal and patients with acute and chronic IHD (CIHD).

 

 

Cell therapy for heart disease after 15 years: Unmet expectations.


 Pharmacol Res. 2017 Feb 21. pii: S1043-6618(16)31000-3. doi: 10.1016/j.phrs.2017.02.015. [Epub ]

Authors: Nigro P, Bassetti B, Cavallotti L, Catto V, Carbucicchio C, Pompilio G.

Abstract
Over the past two decades cardiac cell therapy (CCT) has emerged as a promising new strategy to cure heart diseases at high unmet need. Thousands of patients have entered clinical trials for acute or chronic heart conditions testing different cell types, including autologous or allogeneic bone marrow (BM)-derived mononuclear or selected cells, BM- or adipose tissue-derived mesenchymal cells, or cardiac resident progenitors based on their potential ability to regenerate scarred or dysfunctional myocardium. Nowadays, the original enthusiasm surrounding the regenerative medicine field has been cushioned by a cumulative body of evidence indicating an inefficient or modest efficacy of CCT in improving cardiac function, along with the continued lack of indisputable proof for long-term prognostic benefit. In this review, we have firstly comprehensively outlined the positive and negative results of cell therapy studies in patients with acute myocardial infarction, refractory angina and chronic heart failure. Next, we have discussed cell therapy- and patient-related variables (e.g. cell intrinsic and extrinsic characteristics as well as criteria of patient selection and proposed methodologies) that might have dampened the efficacy of past cell therapy trials. Finally, we have addressed critical factors to be considered before embarking on further clinical trials.

 

Therapeutic use of stem cells for cardiovascular disease.
 


 
Clin Transl Med. 2016 Dec;5(1):34. doi: 10.1186/s40169-016-0116-3. Epub 2016 Aug 18.

Authors: Faiella W, Atoui R.

Abstract
 

Stem cell treatments are a desirable therapeutic option to regenerate myocardium and improve cardiac function after myocardial infarction. Several different types of cells have been explored, each with their own benefits and limitations. Induced pluripotent stem cells possess an embryonic-like state and therefore have a high proliferative capacity, but they also pose a risk of teratoma formation. Mesenchymal stem cells have been investigated from both bone marrow and adipose tissue. Their immunomodulatory characteristics may permit the use of allogeneic cells as universal donor cells in the future. Lastly, studies have consistently shown that cardiac stem cells are better able to express markers of cardiogenesis compared to other cell types, as well improve cardiac function. The ideal source of stem cells depends on multiple factors such as the ease of extraction/isolation, effectiveness of engraftment, ability to differentiate into cardiac lineages and effect on cardiac function. Although multiple studies highlight the benefits and limitations of each cell type and reinforce the successful potential use of these cells to regenerate damaged myocardium, more studies are needed to directly compare cells from various sources. It is interesting to note that research using stem cell therapies is also expanding to treat other cardiovascular diseases including non-ischemic cardiomyopathies.

 
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