Cardiovascular Cell Therapy Research Network

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Cardiovascular Cell Therapy Research Network (CCTRN) is a network of physicians, scientists, and support staff dedicated to studying stem cell therapy for treating heart disease. The CCTRN is funded by the National Institutes of Health (NIH) and includes expert researchers with experience in cardiovascular care at seven stem cell centers in the United States. The goals of the Network are to complete research studies that will potentially lead to more effective treatments for patients with cardiovascular disease, and to share knowledge quickly with the healthcare community.

Contents

Mission statement

The mission of the CCTRN is to achieve public health advances for the treatment of cardiovascular diseases, through the conduct and dissemination of collaborative research leading to evidence-based treatment options and improved outcome for patients with heart disease. [1]

Components of the Network

The sponsor

The National Heart, Lung, and Blood Institute (NHLBI) is one of 27 institutes/centers of the National Institutes of Health (NIH) and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The NHLBI plans and directs research in the development and evaluation of interventions and devices related to prevention, treatment, and rehabilitation of patients with such diseases and disorders.

The Coordinating Center for Clinical Trials

Since 1971, the Coordinating Center for Clinical Trials () at The University of Texas School of Public Health has played a leading role in cardiovascular disease and vision research by serving as a coordinating center for 25 nationwide multicenter clinical trials. The CCCT's primary function is to provide and coordinate all operations, procedures, and activities of a large-scale randomized controlled clinical trial. The CCCT serves as the Data Coordinating Center for the CCTRN. The DCC was led by Lemuel Moye (2006-2019) and Barry R. Davis (2019-2021).

The clinical sites

The CCTRN includes seven stem cell centers in the United States with experience and expertise in clinical trials studying treatments for heart disease and peripheral artery disease. These sites include:

Body of work

In July 2008, the CCTRN opened enrollment in two studies in patients who had recently had heart attacks: TIME [2] ((NCT00684021)) and LateTIME [3] ((NCT00684060)). The purpose of these studies was to determine if stem cells safely taken from an individual's bone marrow could be transplanted back into the injured heart muscle of the individual and improve the heart's ability to pump following a heart attack, as well as to determine the best time for transplanting the cells following a heart attack. The results of both studies were presented at the American Heart Association (AHA) Scientific meetings in 2011 (LateTIME) and 2012 (TIME), and simultaneously published in JAMA. [4] [5]

In March 2009, the CCTRN opened enrollment in a heart failure study: FOCUS [6] ((NCT00824005)). The purpose of this study was to determine the safety and effectiveness of injecting bone marrow stem cells into heart muscle in an attempt to promote blood vessel growth that could potentially improve the blood supply in hearts that are failing. This study recruited patients who had heart failure, but would no longer benefit from other forms of standard treatment such as surgery or coronary artery repair procedures such as balloon angioplasty or stent placement. The results of this study were presented at the American College of Cardiology (ACC) Annual Meeting in 2012 and simultaneously published in JAMA. [7]

In June 2013, CCTRN opened enrollment in a study in peripheral artery disease: PACE [8] ((NCT01774097)). The purpose of this study was to determine the safety and effectiveness of bone marrow-derived stem cell therapy on improving blood flow and walking ability in patients with peripheral artery disease. The results of this study were published in Circulation in 2017. [9]

In October 2015, CCTRN opened enrollment in a study in heart failure: CONCERT-HF [10] (NCT02501811). The purpose of the study was to determine whether giving autologous Mesenchymal Stem Cells (MSCs) and/or C-kit+ cells to patients with heart muscle damage is safe and to help us learn whether these treatments improve heart function for people who are not ideal candidates for other forms of standard therapy such as surgery. The results of this study were published in the European Journal of Heart Failure in 2021. [11]

In September 2016, CCTRN opened enrollment in a study in anthracycline-induced cardiomyopathy (AIC): SENECA [12] (NCT02509156). The purpose of the study was to determine whether giving allogeneic mesenchymal stem cells (MSCs) to patients with AIC is safe and whether these treatments improve heart function. The results of this study were published in JACC CardioOncology in 2020. [13]

Related Research Articles

Coronary artery disease Disease characterized by plaque building up in the arteries of the heart

Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of plaque (atherosclerosis) in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, myocardial infarction, and sudden cardiac death. A common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. Occasionally it may feel like heartburn. Usually symptoms occur with exercise or emotional stress, last less than a few minutes, and improve with rest. Shortness of breath may also occur and sometimes no symptoms are present. In many cases, the first sign is a heart attack. Other complications include heart failure or an abnormal heartbeat.

Stem cell Undifferentiated biological cells that can differentiate into specialized cells

In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.

Statin Class of drugs used to lower cholesterol levels

Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs.

Myelodysplastic syndrome Diverse collection of blood-related cancers

A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, so do not become healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include feeling tired, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.

Bone marrow Semi-solid tissue in the spongy portions of bones

Bone marrow is a semi-solid tissue found within the spongy portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production. It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg (161 lbs) will have around 3.7 kg (8 lbs) of bone marrow.

Severe combined immunodeficiency Medical condition

Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in differing clinical presentations. SCID involves defective antibody response due to either direct involvement with B lymphocytes or through improper B lymphocyte activation due to non-functional T-helper cells. Consequently, both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is the most severe form of primary immunodeficiencies, and there are now at least nine different known genes in which mutations lead to a form of SCID. It is also known as the bubble boy disease and bubble baby disease because its victims are extremely vulnerable to infectious diseases and some of them, such as David Vetter, have become famous for living in a sterile environment. SCID is the result of an immune system so highly compromised that it is considered almost absent.

Dyslipidemia is an abnormal amount of lipids in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). ASCVD includes coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.

Hairy cell leukemia Hematological malignancy

Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a subtype of chronic lymphocytic leukemia (CLL). Hairy cell leukemia makes up about 2% of all leukemias, with fewer than 2,000 new cases diagnosed annually in North America and Western Europe combined.

Cell therapy Therapy in which cellular material is injected into a patient

Cell therapy is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-cells capable of fighting cancer cells via cell-mediated immunity in the course of immunotherapy, or grafting stem cells to regenerate diseased tissues.

Waldenström macroglobulinemia is a type of cancer affecting two types of B cells: lymphoplasmacytoid cells and plasma cells. Both cell types are white blood cells. It is characterized by having high levels of a circulating antibody, immunoglobulin M (IgM), which is made and secreted by the cells involved in the disease. Waldenström macroglobulinemia is an "indolent lymphoma" and a type of lymphoproliferative disease which shares clinical characteristics with the indolent non-Hodgkin lymphomas. It is commonly classified as a form of plasma cell dyscrasia, similar to other plasma cell dyscrasias that, for example, lead to multiple myeloma. Waldenström macroglobulinemia is commonly preceded by two clinically asymptomatic but progressively more pre-malignant phases, IgM monoclonal gammopathy of undetermined significance and smoldering Waldenström macroglobulinemia. The Waldenström macroglobulinemia spectrum of dysplasias differs from other spectrums of plasma cell dyscrasias in that it involves not only aberrant plasma cells but also aberrant lymphoplasmacytoid cells and that it involves IgM while other plasma dyscrasias involve other antibody isoforms.

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition. As of 2016, the only established therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone-marrow transplantation, but the cells can also be derived from umbilical cord blood. Research is underway to develop various sources for stem cells as well as to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes and heart disease.

X-linked severe combined immunodeficiency Medical condition

X-linked severe combined immunodeficiency (X-SCID) is an immunodeficiency disorder in which the body produces very few T cells and NK cells.

RANKL Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.

Endothelial progenitor cell is a term that has been applied to multiple different cell types that play roles in the regeneration of the endothelial lining of blood vessels. Outgrowth endothelial cells are an EPC subtype committed to endothelial cell formation. Despite the history and controversy, the EPC in all its forms remains a promising target of regenerative medicine research.

In cardiology neocardiogenesis is the homeostatic regeneration, repair and renewal of sections of malfunctioning adult cardiovascular tissue. This includes a combination of cardiomyogenesis and angiogenesis.

Treatment of cancer Overview of various treatment possibilities for cancer

Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy and synthetic lethality, most commonly as a series of separate treatments. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient. Cancer genome sequencing helps in determining which cancer the patient exactly has for determining the best therapy for the cancer. A number of experimental cancer treatments are also under development. Under current estimates, two in five people will have cancer at some point in their lifetime.

Adult mesenchymal stem cells are being used by researchers in the fields of regenerative medicine and tissue engineering to artificially reconstruct human tissue which has been previously damaged. Mesenchymal stem cells are able to differentiate, or mature from a less specialized cell to a more specialized cell type, to replace damaged tissues in various organs.

Cellular cardiomyoplasty, or cell-based cardiac repair, is a new potential therapeutic modality in which progenitor cells are used to repair regions of damaged or necrotic myocardium. The ability of transplanted progenitor cells to improve function within the failing heart has been shown in experimental animal models and in some human clinical trials. In November 2011, a large group of collaborators at Minneapolis Heart Institute Foundation at Abbott Northwestern found no significant difference in left ventricular ejection fraction (LVEF) or other markers, between a group of patients treated with cellular cardiomyoplasty and a group of control patients. In this study, all patients were post MI, post percutaneous coronary intervention (PCI) and that infusion of progenitor cells occurred 2–3 weeks after intervention. In a study that is currently underway, however, more positive results were being reported: In the SCIPIO trial, patients treated with autologous cardiac stem cells post MI have been reported to be showing statistically significant increases in LVEF and reduction in infarct size over the control group at four months after implant. Positive results at the one-year mark are even more pronounced. Yet the SCIPIO trial "was recently called into question". Harvard University is "now investigating the integrity of some of the data". The Lancet recently published a non-specific ‘Expression of concern’ about the paper. Subsequently, another preclinical study also raised doubts on the rationale behind using this special kind of cell, as it was found that the special cells only have a minimal ability in generating new cardiomyocytes. Some specialists therefore now raise concerns to continue.

HIV/AIDS research Field of immunology research

HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

The Q-Symbio study was an international multi-center clinical trial that was reported in the Journal of the American College of Cardiology: Heart Failure in September 2014.

References

  1. ↑ Simari R.D., Moyé L.A., Skarlatos S.I,, Ellis S.G., Zhao D.X., Willerson J.T., Henry T.D., Pepine C.J. Development of a network to test strategies in cardiovascular cell delivery: the NHLBI-sponsored Cardiovascular Cell Therapy Research Network (CCTRN). J. Cardiovasc. Transl. Res. 2010 Feb;3(1):30-6.
  2. ↑ Traverse J.H., Henry T.D., Vaughan D., Ellis S.G., Pepine C.J., Willerson J.T., Zhao D.X.M., Piller L.B., Penn M.S., Byrne B.J., Perin E.C., Gee A.P., Hatzopoulous A.K., McKenna D.H., Forder J.R., Taylor D.A., Cogle C.R., Olson R.E., Jorgenson B.C., Sayre S.L., Vojvodic R.W., Gordon D.J., Skarlatos S.I., Moyé L.A., Simari R.D. for the Cardiovascular Cell Therapy Research Network. Rationale and Design for TIME: A Phase-II, Randomized, Double-Blind, Placebo-Controlled Pilot Trial Evaluating the Safety and Effect of Timing of Administration of Bone Marrow Mononuclear Cells Following Acute Myocardial Infarction. Journal American Heart Association. 2009 Sep;158(3):356-63.
  3. ↑ Traverse J.H., Henry T.D., Vaughan D.E., Ellis S.G., Pepine C.J., Willerson J.T., Zhao D.X.M., Simpson L., Penn M.S., Byrne B.J., Perin E.C., Gee A.P., Hatzopoulous A.K., McKenna D.H., Forder J.R., Taylor D.A., Cogle C.R., Baraniuk S., Olson R.E., Jorgenson B.E., Sayre, S.L., Vojvodic, R.W., Gordon, D.J., Skarlatos, S.I., Moye, L.A., Simari, R.D. for the Cardiovascular Cell Therapy Research Network (CCTRN). Rationale and Design for Late TIME: A Phase-II, Randomized, Placebo-Controlled, Double-Blind Pilot Trial Evaluating the Safety and Effect of Administration of Bone Marrow Mononuclear Cells Two to Three Weeks Following Acute Myocardial Infarction. Texas Heart Institute Journal 2010 Aug;37(4):412-420.
  4. ↑ Traverse J.H., Henry T.D., Ellis S.G., Pepine C.J., Willerson J.T., Zhao D.X.M., Forder J.R., Byrne B.J., Hatzopoulos A.K., Penn M.S., Perin E.C., Baran K.W., Chambers J.W., Lambert C.E., Raveendran G., Simon D.I., Vaughan D.E., Simpson L.M., Gee A.P., Taylor D.A., Cogle C.R., Thomas J.D., Silva G.V., Jorgenson B.C., Olson R.E., Bowman S.D., Francescon J.L., Geither C.L., Handberg E.M., Smith D., Baraniuk S., Piller L.B., Loghin C., Aguilar D., Richman S.J., Zierold-Fairman C., Bettencourt J., Sayre S.L., Vojvodic R.W., Skarlatos S.I., Gordon D.J., Ebert R.F., Kwak M., Moyé L.A., Simari R.D. for the Cardiovascular Cell Therapy Research Network (CCTRN). Effect of Intracoronary Delivery of Autologous Bone Marrow Mononuclear Cells Two to Three Weeks Following Acute Myocardial Infarction on Left-Ventricular Function: The LateTIME Randomized Trial. JAMA. 2011 Nov; 306(19):2110-2119.
  5. ↑ Traverse J.H., Henry T.D., Pepine C.J., Willerson J.T., Zhao D.X.M., Ellis S.G., Forder J.R., Anderson R.D., Hatzopoulos A.K., Penn M.S., Perin E.C., Chambers J.W., Baran K.W., Raveendran G., Lambert C.E., Lerman, A, Simon D.I., Vaughan D.E., Lai D., Gee A.P., Taylor D.A., Cogle C.R., Thomas J.D., Silva G.V., Olson R.E., Bowman S.D., Francescon J.L., Geither C.L., Handberg E.M., Kappenman C., Westbrook L., Piller L.B., Simpson, L.M., Baraniuk S., Loghin C., Aguilar D., Richman S.J., Zierold-Fairman C., Spoon, D.B., Bettencourt J., Sayre S.L., Vojvodic R.W., Skarlatos S.I., Gordon D.J., Ebert R.F., Kwak M., Moyé L.A., Simari R.D. for the Cardiovascular Cell Therapy Research Network (CCTRN). Effect of Use and Timing of Bone Marrow Mononuclear Cell Delivery on Left Ventricular Function After Acute Myocardial Infarction: The TIME Randomized Trial. JAMA. 2012 Dec; 308(22):2380-9.
  6. ↑ Willerson J.T., Perin E.C., Ellis S.G., Pepine C.J., Henry T.D., Zhao D.X.M., Lai D., Penn M.S., Byrne B.J., Silva G., Gee A., Traverse J.H., Hatzopoulos A.K., Forder J.R., Martin D., Kronenberg M., Taylor D.A., Cogle C.R., Baraniuk S., Westbrook L., Sayre S.L., Vojvodic R.W., Gordon D.J., Skarlatos S.I., Moyé L.A., Simari R.D., for the Cardiovascular Cell Therapy Research Network (CCTRN) Rationale and Design for the Intramyocardial Injection of Autologous Bone Marrow Mononuclear Cells for Patients with Chronic Ischemic Heart Disease and Left Ventricular Dysfunction Trial (FOCUS). American Heart Journal. 2010 Aug; 160(2):215-223.
  7. ↑ Perin E.C., Willerson J.T., Pepine C.J., Henry T.D., Ellis S.G., Zhao D.X.M., Silva G.V., Lai D., Thomas J.D., Kronenberg M.W., Martin A.D., Anderson R.D., Traverse J.H., Penn M.S., Anwaruddin S., Hatzopoulos A.K., Gee A.P., Taylor D.A., Cogle C.R., Smith D., Westbrook L., Handberg E.M., Olson R.E., Geither C.L., Bowman S.D., Francescon J.L., Baraniuk S., Piller L.B., Simpson, L.M., Loghin C., Aguilar D., Richman S.J., Zierold-Fairman C., Spoon, D.B., Bettencourt J., Sayre S.L., Vojvodic R.W., Skarlatos S.I., Gordon D.J., Ebert R.F., Kwak M., Moyé L.A., Simari R.D. for the Cardiovascular Cell Therapy Research Network (CCTRN). Effect of Transendocardial Delivery of Autologous Bone Marrow Mononuclear Cells on Functional Capacity, Left Ventricular Function, and Perfusion in Chronic Ischemic Heart Failure: The FOCUS-CCTRN Trial. JAMA. 2012 April; 307(16):1717-26.
  8. ↑ Perin EC, Murphy M, Cooke JP, Moyé L, Henry TD, Bettencourt J, Gahremanpour A, Leeper N, Anderson RD, Hiatt WR, Lima JA, Venkatesh B, Sayre SL, Vojvodic RW, Taylor DA, Ebert RF, Hirsch AT; Cardiovascular Cell Therapy Research Network. Rationale and design for PACE: patients with intermittent claudication injected with ALDH bright cells. Am Heart J. 2014 Nov;168(5):667-73. doi: 10.1016/j.ahj.2014.07.021. Epub 2014 Jul 30. PMID 25440794; PMCID: PMC4254580.
  9. ↑ Perin EC, Murphy MP, March KL, Bolli R, Loughran J, Yang PC, Leeper NJ, Dalman RL, Alexander J, Henry TD, Traverse JH, Pepine CJ, Anderson RD, Berceli S, Willerson JT, Muthupillai R, Gahremanpour A, Raveendran G, Velasquez O, Hare JM, Hernandez Schulman I, Kasi VS, Hiatt WR, Ambale-Venkatesh B, Lima JA, Taylor DA, Resende M, Gee AP, Durett AG, Bloom J, Richman S, G'Sell P, Williams S, Khan F, Gyang Ross E, Santoso MR, Goldman J, Leach D, Handberg E, Cheong B, Piece N, DiFede D, Bruhn-Ding B, Caldwell E, Bettencourt J, Lai D, Piller L, Simpson L, Cohen M, Sayre SL, Vojvodic RW, Moyé L, Ebert RF, Simari RD, Hirsch AT; Cardiovascular Cell Therapy Research Network (CCTRN). Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN PACE Trial (Patients With Intermittent Claudication Injected With ALDH Bright Cells). Circulation. 2017 Apr 11;135(15):1417-1428. doi: 10.1161/CIRCULATIONAHA.116.025707. Epub 2017 Feb 16.
  10. ↑ Bolli R, Hare JM, March KL, Pepine CJ, Willerson JT, Perin EC, Yang PC, Henry TD, Traverse JH, Mitrani RD, Khan A, Hernandez-Schulman I, Taylor DA, DiFede DL, Lima JAC, Chugh A, Loughran J, Vojvodic RW, Sayre SL, Bettencourt J, Cohen M, Moyé L, Ebert RF, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Rationale and Design of the CONCERT-HF Trial (Combination of Mesenchymal and c-kit+ Cardiac Stem Cells As Regenerative Therapy for Heart Failure). Circ Res. 2018 Jun 8;122(12):1703-1715. doi: 10.1161/CIRCRESAHA.118.312978. Epub 2018 Apr 27. PMID 29703749; PMCID: PMC5993622.
  11. ↑ Bolli R, Mitrani RD, Hare JM, Pepine CJ, Perin EC, Willerson JT, Traverse JH, Henry TD, Yang PC, Murphy MP, March KL, Schulman IH, Ikram S, Lee DP, O'Brien C, Lima JA, Ostovaneh MR, Ambale-Venkatesh B, Lewis G, Khan A, Bacallao K, Valasaki K, Longsomboon B, Gee AP, Richman S, Taylor DA, Lai D, Sayre SL, Bettencourt J, Vojvodic RW, Cohen ML, Simpson L, Aguilar D, Loghin C, Moyé L, Ebert RF, Davis BR, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). A Phase II study of autologous mesenchymal stromal cells and c-kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT-HF trial. Eur J Heart Fail. 2021 Apr 3. doi: 10.1002/ejhf.2178. Epub ahead of print. PMID 33811444.
  12. ↑ Bolli R, Hare JM, Henry TD, Lenneman CG, March KL, Miller K, Pepine CJ, Perin EC, Traverse JH, Willerson JT, Yang PC, Gee AP, Lima JA, Moyé L, Vojvodic RW, Sayre SL, Bettencourt J, Cohen M, Ebert RF, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial. Am Heart J. 2018 Jul;201:54-62. doi: 10.1016/j.ahj.2018.02.009. Epub 2018 Apr 4. PMID 29910056; PMCID: PMC7282462.
  13. ↑ Bolli R, Perin EC, Willerson JT, Yang PC, Traverse JH, Henry TD, Pepine CJ, Mitrani RD, Hare JM, Murphy MP, March KL, Ikram S, Lee DP, O'Brien C, Durand JB, Miller K, Lima JA, Ostovaneh MR, Ambale-Venkatesh B, Gee AP, Richman S, Taylor DA, Sayre SL, Bettencourt J, Vojvodic RW, Cohen ML, Simpson LM, Lai D, Aguilar D, Loghin C, Moyé L, Ebert RF, Davis BR, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Allogeneic Mesenchymal Cell Therapy in Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The CCTRN SENECA Trial. JACC CardioOncol. 2020 Nov;2(4):581-595. doi: 10.1016/j.jaccao.2020.09.001. Epub 2020 Dec 22. PMID 33403362; PMCID: PMC7781291.
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