Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Jul 21;7(7):CD013433.
doi: 10.1002/14651858.CD013433.pub2.

Stem cell therapy for dilated cardiomyopathy

Rienzi Diaz-Navarro  1 , Gerard Urrútia  2 , John Gf Cleland  3 , Daniel Poloni  1 , Francisco Villagran  1 , Roberto Acosta-Dighero  4   5 , Shrikant I Bangdiwala  6 , Gabriel Rada  7 , Eva Madrid  8   4
Affiliations
Meta-Analysis

Stem cell therapy for dilated cardiomyopathy

Rienzi Diaz-Navarro et al. Cochrane Database Syst Rev. .

Abstract

Background: Stem cell therapy (SCT) has been proposed as an alternative treatment for dilated cardiomyopathy (DCM), nonetheless its effectiveness remains debatable.

Objectives: To assess the effectiveness and safety of SCT in adults with non-ischaemic DCM.

Search methods: We searched CENTRAL in the Cochrane Library, MEDLINE, and Embase for relevant trials in November 2020. We also searched two clinical trials registers in May 2020.

Selection criteria: Eligible studies were randomized controlled trials (RCT) comparing stem/progenitor cells with no cells in adults with non-ischaemic DCM. We included co-interventions such as the administration of stem cell mobilizing agents. Studies were classified and analysed into three categories according to the comparison intervention, which consisted of no intervention/placebo, cell mobilization with cytokines, or a different mode of SCT. The first two comparisons (no cells in the control group) served to assess the efficacy of SCT while the third (different mode of SCT) served to complement the review with information about safety and other information of potential utility for a better understanding of the effects of SCT.

Data collection and analysis: Two review authors independently screened all references for eligibility, assessed trial quality, and extracted data. We undertook a quantitative evaluation of data using random-effects meta-analyses. We evaluated heterogeneity using the I² statistic. We could not explore potential effect modifiers through subgroup analyses as they were deemed uninformative due to the scarce number of trials available. We assessed the certainty of the evidence using the GRADE approach. We created summary of findings tables using GRADEpro GDT. We focused our summary of findings on all-cause mortality, safety, health-related quality of life (HRQoL), performance status, and major adverse cardiovascular events.

Main results: We included 13 RCTs involving 762 participants (452 cell therapy and 310 controls). Only one study was at low risk of bias in all domains. There were many shortcomings in the publications that did not allow a precise assessment of the risk of bias in many domains. Due to the nature of the intervention, the main source of potential bias was lack of blinding of participants (performance bias). Frequently, the format of the continuous data available was not ideal for use in the meta-analysis and forced us to seek strategies for transforming data in a usable format. We are uncertain whether SCT reduces all-cause mortality in people with DCM compared to no intervention/placebo (mean follow-up 12 months) (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.54 to 1.31; I² = 0%; studies = 7, participants = 361; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection in people with DCM (data could not be pooled; studies = 7; participants = 361; very low-certainty evidence). We are uncertain whether SCT improves HRQoL (standardized mean difference (SMD) 0.62, 95% CI 0.01 to 1.23; I² = 72%; studies = 5, participants = 272; very low-certainty evidence) and functional capacity (6-minute walk test) (mean difference (MD) 70.12 m, 95% CI -5.28 to 145.51; I² = 87%; studies = 5, participants = 230; very low-certainty evidence). SCT may result in a slight functional class (New York Heart Association) improvement (data could not be pooled; studies = 6, participants = 398; low-certainty evidence). None of the included studies reported major adverse cardiovascular events as defined in our protocol. SCT may not increase the risk of ventricular arrhythmia (data could not be pooled; studies = 8, participants = 504; low-certainty evidence). When comparing SCT to cell mobilization with granulocyte-colony stimulating factor (G-CSF), we are uncertain whether SCT reduces all-cause mortality (RR 0.46, 95% CI 0.16 to 1.31; I² = 39%; studies = 3, participants = 195; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection (studies = 1, participants = 60; very low-certainty evidence). SCT may not improve HRQoL (MD 4.61 points, 95% CI -5.62 to 14.83; studies = 1, participants = 22; low-certainty evidence). SCT may improve functional capacity (6-minute walk test) (MD 140.14 m, 95% CI 119.51 to 160.77; I² = 0%; studies = 2, participants = 155; low-certainty evidence). None of the included studies reported MACE as defined in our protocol or ventricular arrhythmia. The most commonly reported outcomes across studies were based on physiological measures of cardiac function where there were some beneficial effects suggesting potential benefits of SCT in people with non-ischaemic DCM. However, it is unclear if this intermediate effects translates into clinical benefits for these patients. With regard to specific aspects related to the modality of cell therapy and its delivery, uncertainties remain as subgroup analyses could not be performed as planned, making it necessary to wait for the publication of several studies that are currently in progress before any firm conclusion can be reached.

Authors' conclusions: We are uncertain whether SCT in people with DCM reduces the risk of all-cause mortality and procedural complications, improves HRQoL, and performance status (exercise capacity). SCT may improve functional class (NYHA), compared to usual care (no cells). Similarly, when compared to G-CSF, we are also uncertain whether SCT in people with DCM reduces the risk of all-cause mortality although some studies within this comparison observed a favourable effect that should be interpreted with caution. SCT may not improve HRQoL but may improve to some extent performance status (exercise capacity). Very low-quality evidence reflects uncertainty regarding procedural complications. These suggested beneficial effects of SCT, although uncertain due to the very low certainty of the evidence, are accompanied by favourable effects on some physiological measures of cardiac function. Presently, the most effective mode of administration of SCT and the population that could benefit the most is unclear. Therefore, it seems reasonable that use of SCT in people with DCM is limited to clinical research settings. Results of ongoing studies are likely to modify these conclusions.

PubMed Disclaimer

Conflict of interest statement

The performance of this review was free of any real or perceived bias introduced by receipt of any benefit in cash or kind, or any subsidy derived from any source that may have or be perceived to have an interest in the outcomes of the review.

RD: none.

GU: has participated in several educational activities (workshops) and has provided consultancy to several laboratories, but has not been paid for it (money was paid to the institution where he works: Clinical Epidemiology Service, at the Hospital de la Santa Creu i Sant Pau).

JC: has consulted widely with other healthcare companies (Amgen, Novartis, Stealth Biopharmaceuticals, Bayer, Philips, Servier, Pharma Nord, Pharmacosmos, Vifor, HeartFelt Technologies, PharmaIn and Viscardia) but not on the topic of stem cells. He also received payments from the European Society of Cardiology for the development of educational presentations.

DP: none.

FV: none.

RAD: none.

SB: none.

GR: none.

EM: none.

Figures

1
1
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1: Stem cell therapy (SCT; any type) versus control (no intervention or sham intervention), Outcome 1: All‐cause mortality
1.2
1.2. Analysis
Comparison 1: Stem cell therapy (SCT; any type) versus control (no intervention or sham intervention), Outcome 2: Health‐related quality of life
1.3
1.3. Analysis
Comparison 1: Stem cell therapy (SCT; any type) versus control (no intervention or sham intervention), Outcome 3: Performance status – 6‐minute walk test (m)
1.4
1.4. Analysis
Comparison 1: Stem cell therapy (SCT; any type) versus control (no intervention or sham intervention), Outcome 4: Change in left ventricular ejection fraction
1.5
1.5. Analysis
Comparison 1: Stem cell therapy (SCT; any type) versus control (no intervention or sham intervention), Outcome 5: Change in left ventricular end‐systolic volume
1.6
1.6. Analysis
Comparison 1: Stem cell therapy (SCT; any type) versus control (no intervention or sham intervention), Outcome 6: Change in left ventricular end‐diastolic volume
2.1
2.1. Analysis
Comparison 2: Stem cell therapy (SCT; any type) versus peripheral therapy with granulocyte colony‐stimulating factor (G‐CSF), Outcome 1: All‐cause mortality
2.2
2.2. Analysis
Comparison 2: Stem cell therapy (SCT; any type) versus peripheral therapy with granulocyte colony‐stimulating factor (G‐CSF), Outcome 2: Health‐related quality of life
2.3
2.3. Analysis
Comparison 2: Stem cell therapy (SCT; any type) versus peripheral therapy with granulocyte colony‐stimulating factor (G‐CSF), Outcome 3: Performance status – 6‐minute walk test (m)
2.4
2.4. Analysis
Comparison 2: Stem cell therapy (SCT; any type) versus peripheral therapy with granulocyte colony‐stimulating factor (G‐CSF), Outcome 4: Change in left ventricular ejection volume
2.5
2.5. Analysis
Comparison 2: Stem cell therapy (SCT; any type) versus peripheral therapy with granulocyte colony‐stimulating factor (G‐CSF), Outcome 5: Change in left ventricular end‐systolic volume
2.6
2.6. Analysis
Comparison 2: Stem cell therapy (SCT; any type) versus peripheral therapy with granulocyte colony‐stimulating factor (G‐CSF), Outcome 6: Change in left ventricular end‐diastolic volume
2.7
2.7. Analysis
Comparison 2: Stem cell therapy (SCT; any type) versus peripheral therapy with granulocyte colony‐stimulating factor (G‐CSF), Outcome 7: Change in plasma natriuretic peptide levels (BNP and NT‐proBNP)
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD013433

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Hamshere 2015 {published data only}
    1. Arnous S, Mozid A, Mathur A. The Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy (REGENERATE-DCM) trial: study design. Regenerative Medicine 2011;6(4):525-33. - PubMed
    1. EUCTR2009-013112-12-GB. Randomised controlled trial to compare the effects of G-CSF(Granocyte™) and autologous bone marrow progenitor cells on quality of life and left ventricular function In patients with idiopathic dilated cardiomyopathy – REGENERATE-DCM. ddrare.nibiohn.go.jp/cgi-bin/disease_who_e.cgi?id=57 (accessed prior to 1 July 2021).
    1. Hamshere S, Arnous S, Choudhury T, Choudry F, Mozid A, Yeo C, et al. Randomized trial of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with non-ischaemic dilated cardiomyopathy: the REGENERATE-DCM clinical trial. European Heart Journal 2015;36(44):3061-9. [DOI: ] - PMC - PubMed
    1. NCT01302171. Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy (REGEN-DCM). clinicaltrials.gov/ct2/show/NCT01302171 (first received 24 February 2011).
Hare 2017 (POSEIDON‐DCM) {published data only}
    1. Hare JM, DiFede DL, Rieger AC, Florea V, Landin AM, El-Khorazaty J, et al. Randomized comparison of allogeneic versus autologous mesenchymal stem cells for nonischemic dilated cardiomyopathy: POSEIDON-DCM trial. Journal of the American College of Cardiology 2017;69(5):526-37. - PMC - PubMed
    1. Mushtaq M, DiFede DL, Golpanian S, Khan A, Gomes SA, Mendizabal A, et al. Rationale and design of the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy (the POSEIDON-DCM study): a phase I/II, randomized pilot study of the comparative safety and efficacy of transendocardial injection of autologous mesenchymal stem cell vs. allogeneic mesenchymal stem cells in patients with non-ischemic dilated cardiomyopathy. Journal of Cardiovascular Translational Research 2014;7(9):769-80. - PMC - PubMed
    1. Ramireddy A, Brodt CR, Mendizabal AM, DiFede DL, Healy C, Goyal V, et al. Effects of transendocardial stem cell injection on ventricular proarrhythmia in patients with ischemic cardiomyopathy: results from the POSEIDON and TAC-HFT Trials. Stem Cells Translational Medicine 2017;6:1366-72. [DOI: 10.1002/sctm.16-0328] - DOI - PMC - PubMed
Henry 2014 {published data only}
    1. Bruckner BA, Ghodsizad A, Hamman BL, Bull DA, Lattouf OM, Smedira NG, et al. IMPACT-DCM: a randomized, controlled, multi-center phase II trial utilizing expanded autologous bone marrow as sole therapy for dilated cardiomyopathy study update. Journal of Heart and Lung Transplantation 2011;30:79.
    1. Bunge RR, Patel AN, Hamman BL, Lattouf OM, Smedira NG, Bartel RL, et al. Safety and efficacy of ixmyelocel-t, an expanded patient-specific mixed cell product, in dilated cardiomyopathy (IMPACT-DCM). Journal of Heart and Lung Transplantation 2012;31:72-3.
    1. Henry TD, Traverse JH, Hammon BL, East CA, Bruckner B, Remmers AE, et al. Safety and efficacy of ixmyelocel-T: an expanded, autologous multi-cellular therapy, in dilated cardiomyopathy. Circulation Research 2014;115(8):730-7. [DOI: 10.1161/CIRCRESAHA.115.304554] - DOI - PubMed
    1. Patel AN, Hamman BL, Bruckner B, Lattouf OM, Smedira NG, East C, et al. Safety and efficacy of ixmyelocel-T, an expanded patient-specific mixed cell product, in dilated cardiomyopathy (IMPACT-DCM). Journal of Cardiac Failure 2011;17:58.
Martino 2015 (MiHEART) {published data only}
    1. Martino H, Brofman P, Greco O, Bueno R, Bodanese L, Clausell N, et al. Multicentre, randomized, double-blind trial of intracoronary autologous mononuclear bone marrow cell injection in non-ischaemic dilated cardiomyopathy (the dilated cardiomyopathy arm of the MiHeart study). European Heart Journal 2015;36(42):2898-904. - PubMed
    1. Tura BR, Martino HF, Gowdak LH, dos Santos RR, Dohmann HF, Krieger JE, et al. Multicenter randomized trial of cell therapy in cardiopathies MiHeart study. Trials 2007;8:2. - PMC - PubMed
Sant'Anna 2014 (INTRACELL) {published data only}
    1. Sant'Anna RT, Fracasso J, Valle FH, Castro I, Nardi NB, Sant'Anna JR, et al. Direct intramyocardial transthoracic transplantation of bone marrow mononuclear cells for non-ischemic dilated cardiomyopathy: INTRACELL, a prospective randomized controlled trial. Revista Brasileira de Cirurgia Cardiovascular 2014;29(3):437-47. - PMC - PubMed
Seth 2010 (ABCD) {published data only}
    1. Seth S, Bhargava B, Narang R, Mohanty S, Ray R, Gulati G, et al. A randomised trial of Autologous Bone marrow Cells in Dilated cardiomyopathy (ABCD). European Heart Journal 2009;30:501.
    1. Seth S, Bhargava B, Narang R, Ray R, Mohanty S, Gulati G, et al. The ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) trial: a long-term follow-up study. Journal of the American College of Cardiology 2010;55(15):1643-4. - PubMed
    1. Seth S, Narang R, Bhargava B, Ray R, Mohanty S, Gulati G, et al. Percutaneous intracoronary cellular cardiomyoplasty for nonischemic cardiomyopathy: clinical and histopathological results: the first-in-man ABCD (Autologous Bone marrow Cells in Dilated cardiomyopathy) trial. Journal of the American College of Cardiology 2006;48(11):2350-1. - PubMed
Vrtovec 2011 {published data only}
    1. Vrtovec B, Poglajen G, Sever M, Lezaic L, Domanovic D, Cernelc P, et al. Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy. Journal of Cardiac Failure 2011;17(4):272-81. [DOI: ] - PubMed
Vrtovec 2013a (NOGA‐DCM) {published data only}
    1. Vrtovec B, Poglajen G, Lezaic L, Sever M, Domanovic D, Cernelc P, et al. Effects of intracoronary CD34+ stem cell transplantation in non-ischemic dilated cardiomyopathy patients: 5-year follow up. Circulation Research 2012;112:165-73. [DOI: 10.1161/circresaha.112.276519] - DOI - PubMed
    1. Vrtovec B, Poglajen G, Lezaic L, Sever M, Domanovic D, Cernelc P, et al. Effects of intracoronary CD34+stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circulation Research 2013;112(1):165-73. - PubMed
    1. Vrtovec B, Sever M, Domanovic D, Lezaic L, Poglajen G, Cernelc P, et al. Long-term effects of stem cell transplantation in heart failure. Zdravniski Vestnik 2012;81(Suppl II):373-83.
Vrtovec 2013b {published data only}
    1. Vrtovec B, Poglajen G, Lezaic L, Sever M, Domanovic D, Cernelc P, et al. Comparison of clinical effects of transendocardial vs. intracoronary stem cell transplantation in dilated cardiomyopathy. Circulation 2012;126:21. - PubMed
    1. Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D, et al. Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation 2013;128(11):S42-9. - PubMed
Vrtovec 2018 (REMEDIUM) {published data only}
    1. Frljak S, Jaklic M, Zemljic G, Cerar A, Poglajen G, Vrtovec B. CD34(+) cell transplantation improves right ventricular function in patients with nonischemic dilated cardiomyopathy. Stem Cells Translational Medicine 2018;7:168-72. [DOI: 10.1002/sctm.17-0197] - DOI - PMC - PubMed
    1. Vrtovec B, Poglajen G, Sever M, Zemljic G, Frljak S, Cerar A, et al. Effects of repetitive transendocardial CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation Research 2018;123(3):389-96. - PubMed
Wang 2006 {published data only}
    1. Wang JA, Xie XJ, He H, Sun Y, Jiang J, Luo RH, et al. A prospective, randomized, controlled trial of autologous mesenchymal stem cells transplantation for dilated cardiomyopathy. Chung Hua Hsin Hsueh Kuan Ping Tsa Chih 2006;34(2):107-10. - PubMed
Wu 2010 {published data only}
    1. Wu ZH, Yuan MY, Li HM, Qiu JJ, Lao HZ, Wu XY, et al. Autologous peripheral blood stem cells transplantation for the treatment of dilated cardiomyopathy: a 24-month follow-up in 38 cases. Journal of Clinical Rehabilitative Tissue Engineering Research 2010;14(1):121-25. [DOI: ]
Xiao 2017 {published data only}
    1. Xiao W, Guo S, Gao C, Dai G, Gao Y, Li M, et al. A randomized comparative study on the efficacy of intracoronary infusion of autologous bone marrow mononuclear cells and mesenchymal stem cells in patients with dilated cardiomyopathy. International Heart Journal 2017;58(2):238-44. [DOI: ] - PubMed

References to studies excluded from this review

Bartolucci (INNOVA) 2015 {published data only}
    1. Bartolucci J, Verdugo FJ, Carrion F, Abarzúa E, Goset C, Lamich R, et al. Long-term results of intracoronary transplantation of autologous bone marrow cells in dilated cardiomyopathy [Resultados a largo plazo deltrasplante intracoronario de células mononucleares de médula ósea autólogas enpacientes con cardiopatía dilatada de diversa etiología]. Revista Médica de Chile 2015;143(4):415-23. - PubMed
Bartolucci (RIMECARD) 2017 {published data only}
    1. Bartolucci J, Verdugo FJ, González PL, Larrea RE, Abarzua E, Goset C, et al. Safety and efficacy of the intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure: a phase 1/2 randomized controlled trial (RIMECARD trial [Randomized clinical trial of intravenous infusion umbilical cord mesenchymal stem cells on cardiopathy]). Circulation Research 2017;121(10):1192-204. - PMC - PubMed
Bocchi 2010 {published data only}
    1. Bocchi EA, Bacal F, Guimaraes G, Mendroni A, Mocelin A, Filho AE, et al. Granulocyte-colony stimulating factor or granulocyte-colony stimulating factor associated to stem cell intracoronary infusion effects in non ischemic refractory heart failure. International Journal of Cardiology 2010;138(1):94-7. [DOI: ] - PubMed
Butler 2017 {published data only}
    1. Butler J, Epstein SE, Greene SJ, Quyyumi AA, Sikora S, Kim RJ, et al. Intravenous allogeneic mesenchymal stem cells for nonischemic cardiomyopathy: safety and efficacy results of a phase II – a randomized trial. Circulation Research 2017;120(2):332-40. - PubMed
Chen 2008 {published data only}
    1. Chen Y, Gao EM, Gao CY, Xu Y, Huang KJ, Niu ZM, et al. Effects of intracoronary autologous bone marrow mononuclear cells transplantation in patients with dilated cardiomyopathy. Zhonghua Xin Xue GuanBing Za Zhi 2008;36(12):1087-91. - PubMed
Fischer‐Rasokat 2009 {published data only}
    1. Fischer-Rasokat U, Assmus B, Seeger FH, Honold J, Leistner D, Fichtlscherer S, et al. A pilot trial to assess potential effects of selective intracoronary bone marrow-derived progenitor cell infusion in patients with nonischemic dilated cardiomyopathy: final 1-year results of the transplantation of progenitor cells and functional regeneration enhancement pilot trial in patients with nonischemic dilated cardiomyopathy. Circulation. Heart Failure 2009;2(5):417-23. - PubMed
Huang 2006 {published data only}
    1. Huang RC, Yao K, Li YL, Zhang YQ, Xu SK, Shi HY, et al. Transplantation of autologous bone marrow mononuclear cells on patients with idiopathic dilated cardiomyopathy: early results on effect and security. Zhonghua Xin Xue Guan Bing Za Zhi 2006;34(2):111-3. - PubMed
Kakuchaya 2011 {published data only}
    1. Kakuchaya T, Golukhova E, Eremeeva M, Chigogidze N, Aslanidi I, Nikitina T, et al. Bone-marrow progenitor stem cells for the treatment of patients with congestive heart failure of different etiology in a placebo controlled clinical trial. Interactive Cardiovascular and Thoracic Surgery 2011;12:568.
    1. Kakuchaya T, Golukhova E, Eremeeva M, Chigogidze N, Aslanidi I, Shurupova I, et al. Accurate design of randomized placebo-controlled clinical trials for assessment of stem cell effects on cardiac regeneration. European Heart Journal 2011;32:290.
Miyagawa 2017 {published data only}
    1. Miyagawa S, Domae K, Yoshikawa Y, Fukushima S, Nakamura T, Saito A, et al. Phase I clinical trial of autologous stem cell-sheet transplantation therapy for treating cardiomyopathy. Journal American Heart Association 2017;6(4):e003918. - PMC - PubMed
NCT02256501 {unpublished data only}
    1. NCT02256501. Intracoronary transplantation of bone marrow derived mononuclear cells in pediatric cardiomyopathy. clinicaltrials.gov/ct2/show/NCT02256501 (first received 3 October 2014).
Perin (REVASCOR) 2015 {published data only}
    1. Perin EC, Borow KM, Silva GV, DeMaria AN, Marroquin OC, Huang PP, et al. A phase II dose-escalation study of allogeneic mesenchymal precursor cells in patients with ischemic or nonischemic heart failure. Circulation Research 2015;117(6):576-84. - PubMed
Premer 2015 {published data only}
    1. Premer C, Blum A, Bellio MA, Schulman IH, Hurwitz BE, Parker M, et al. Allogeneic mesenchymal stem cells restore endothelial function in heart failure by stimulating endothelial progenitor cells. EBioMedicine 2015;2(5):467-75. - PMC - PubMed
Tompkins 2018 {published data only}
    1. Tompkins BA, Rieger AC, Florea V, Banerjee MN, Natsumeda M, Nigh ED, et al. Comparison of mesenchymal stem cell efficacy in ischemic versus nonischemic dilated cardiomyopathy. Journal of the American Heart Association 2018;7(14):e008460. - PMC - PubMed
Xiao 2012a {published data only}
    1. Xiao WT, Gao LJ, Gao CY, Gao YJ, Dai GY, Li MW, et al. Comparative study on the efficacy of intracoronary infusion with various types of autologous bone marrow stem cells for patients with dilated cardiomyopathy. Zhonghua Xin XueGuan Bing Za Zhi 2012;40(7):575-8. - PubMed
Xiao 2012b {published data only}
    1. Xiao WT, Gao CY, Dai GY, Li MW, Wang XP, Liu HZ, et al. Autologous bone marrow mesenchymal stem cells for myocardial renewal and repair. Chinese Journal of Tissue Engineering Research 2012;16(27):5081-6.
Yau 2019 {published data only}
    1. Yau TM, Pagani FD, Mancini DM, Chang HL, Lala A, Woo YJ, et al. Intramyocardial injection of mesenchymal precursor cells and successful temporary weaning from left ventricular assist device support in patients with advanced heart failure: a randomized clinical trial. JAMA 2019;321(12):1176-86. - PMC - PubMed
Zemljic 2017 {published data only}
    1. Zemljic G, Poglajen G, Sever M, Cukjati M, Frljak S, Androcec V, et al. Electroanatomic properties of the myocardium predict response to CD34+ cell therapy in patients with ischemic and nonischemic heart failure. Journal of Cardiac Failure 2017;23(2):153-60. - PubMed

References to ongoing studies

NCT01957826 {published data only}
    1. NCT01957826. Mesenchymal stem cells for idiopathic dilated cardiomyopathy. clinicaltrials.gov/ct2/show/NCT01957826 (first received 8 October 2013).
NCT02033278 {published data only}
    1. NCT02033278. Infusion intracoronary of mononuclear autologous adult no expanded stem cells of bone marrow on functional recovery in patients with idiopathic dilated cardiomyopathy and heart failure. clinicaltrials.gov/ct2/show/NCT02033278 (first received 10 January 2014).
NCT02293603 {published data only}
    1. NCT02293603. Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC). clinicaltrials.gov/ct2/show/NCT02293603 (first received 18 November 2014).
NCT03797092 {published data only}
    1. NCT03797092. Stem cell therapy in non-ischemic non-treatable dilated cardiomyopathies II: a pilot study. clinicaltrials.gov/ct2/show/NCT03797092 (first received 8 January 2019).

Additional references

Assmus 2002
    1. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002;106(24):3009-17. - PubMed
Assmus 2016
    1. Assmus B, Alakmeh S, De Rosa S, Bönig H, Hermann E, Levy WC, et al. Improved outcome with repeated intracoronary injection of bone marrow-derived cells within a registry: rationale for the randomized outcome trial REPEAT. European Heart Journal 2016;37(21):1659-66. - PMC - PubMed
Bartunek 2013
    1. Bartunek J, Behfar A, Dolatabadi D, Vanderheyden M, Ostojic M, Dens J, et al. Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics. Journal of the American College of Cardiology 2013;61(23):2329-38. - PubMed
Bartunek 2016
    1. Bartunek J, Davison B, Sherman W, Povsic T, Henry TD, Gersh B, et al. Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design. European Journal of Heart Failure 2016;18(2):160-8. - PMC - PubMed
Bartunek 2017
    1. Bartunek J, Terzic A, Davison BA, Filippatos GS, Radovanovic S, Beleslin B, et al. Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial. European Heart Journal 2017;38(9):648-60. - PMC - PubMed
Bartunek 2018
    1. Bartunek J, Terzic A, Behfar A, Wijns W. Clinical experience with regenerative therapy in heart failure: advancing care with cardiopoietic stem cell interventions. Circulation Research 2018;122(10):1344-6. - PMC - PubMed
Behfar 2014
    1. Behfar A, Crespo-Diaz R, Terzic A, Gersh BJ. Cell therapy for cardiac repair-lessons from clinical trials. Nature Reviews. Cardiology 2014;11:232-46. - PubMed
Behfar 2016
    1. Behfar A, Gersh B, Terzic A. Repetition rescues regenerative reserve. European Heart Journal 2016;37(21):1667-70. - PubMed
Blau 2001
    1. Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function? Cell 2001;105(7):829-41. - PubMed
Blau 2019
    1. Blau HM, Daley GQ. Stem cells in the treatment of disease. New England Journal of Medicine 2019;380(18):1748-60. - PubMed
Bozkurt 2016
    1. Bozkurt B, Colvin M, Cook J, Cooper JT, Deswal A, Fonarow GC, et al. Current diagnostic and treatment strategies for specific dilated cardiomyopathies: a scientific statement from the American Heart Association. Circulation 2016;134:e579-646. - PubMed
Chien 2019
    1. Chien KR, Frisén J, Fritsche-Danielson R, Melton DA, Murry CE, Weissman IL. Regenerating the field of cardiovascular cell therapy. Nature Biotechnology 2019;37(3):232-7. - PubMed
Choudry 2016
    1. Choudry F, Hamshere S, Saunders N, Veerapen J, Bavnbek K, Knight C, et al. A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial. European Heart Journal 2016;37(3):256-63. - PMC - PubMed
Cohen 1988
    1. Cohen J. Statistical Power Analysis in the Behavioural Sciences. 2nd edition. Hillsdale (NJ): Lawrence Erlbaum Associates, Inc, 1988.
Covidence [Computer program]
    1. Veritas Health Innovation Covidence. Melbourne, Australia: Veritas Health Innovation, accessed prior to 1 July 2021. Available at covidence.org.
Dec 1994
    1. Dec GW, Fuster V. Idiopathic dilated cardiomyopathy. New England Journal of Medicine 1994;331:1564-75. - PubMed
Deeks 2017
    1. Deeks JJ, Higgins JP, Altman DG, on behalf of the Cochrane Statistical Methods Group. Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017). Cochrane, 2017. Available from training.cochrane.org/handbook/archive/v5.2.
DerSimonian 1986
    1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clinical Trials 1986;7(3):177-88. - PubMed
Díaz 1987
    1. Díaz RA, Obasohan A, Oakley CM. Prediction of outcome in dilated cardiomyopathy. British Heart Journal 1987;58(4):393-9. - PMC - PubMed
Dunlay 2012
    1. Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM. Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circulation Heart Failure 2012;5(6):720-6. - PMC - PubMed
Egger 1997
    1. Egger M, Smith GD, Schneider M, Christoph M. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629. - PMC - PubMed
Erbs 2005
    1. Erbs S, Linke A, Adams V, Lenk K, Thiele H, Diederich KW, et al. Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study. Circulation Research 2005;97(8):756-62. - PubMed
Fisher 2015
    1. Fisher SA, Zhang H, Doree C, Mathur A, Martin-Rendon E. Stem cell treatment for acute myocardial infarction. Cochrane Database of Systematic Reviews 2015, Issue 9. Art. No: CD006536. [DOI: 10.1002/14651858.CD006536.pub4] - DOI - PMC - PubMed
Fisher 2016a
    1. Fisher SA, Doree C, Mathur A, Taggart DP, Martin-Rendon E. Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Cochrane Database of Systematic Reviews 2016, Issue 12. Art. No: CD007888. [DOI: 10.1002/14651858.CD007888.pub3] - DOI - PMC - PubMed
Fisher 2016b
    1. Fisher SA, Doree C, Taggart DP, Mathur A, Martin-Rendon E. Cell therapy for heart disease: trial sequential analyses of two Cochrane reviews. Clinical Pharmacology and Therapeutics 2016;100(1):88-101. - PubMed
Frljak 2018
    1. Frljak S, Jaklic M, Zemljic G, Cerar A, Poglajen G, Vrtovec B. CD34+ cell transplantation improves right ventricular function in patients with nonischemic dilated cardiomyopathy. Stem Cells Translational Medicine 2018;7:168-72. - PMC - PubMed
Fuster 1981
    1. Fuster V, Gersh BJ, Tajik AJ, Brandenburg RO, Frye RL. The natural history of idiopathic dilated cardiomyopathy. American Journal of Cardiology 1981;47(3):525-31. - PubMed
GRADEpro GDT [Computer program]
    1. McMaster University (developed by Evidence Prime) GRADEpro GDT. Hamilton (ON): McMaster University (developed by Evidence Prime), accessed prior to 11 September 2019. Available at gradepro.org.
Harada 2005
    1. Harada M, Qin Y, Takano H, Minamino T, Zou Y, Toko H, et al. G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nature Medicine 2005;11:305-11. - PubMed
Harbord 2006
    1. Harbord RM, Egger M, Sterne JA. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Statistics in Medicine 2006;25(20):3443-57. - PubMed
Hare 2009
    1. Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, et al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. Journal of the American College of Cardiology 2009;54(24):2277-86. - PMC - PubMed
Hare 2017
    1. Hare JM, DiFede DL, Rieger AC, Florea V, Landin AM, El-Khorazaty J, et al. Randomized comparison of allogeneic versus autologous mesenchymal stem cells for nonischemic dilated cardiomyopathy: POSEIDON-DCM trial. Journal of the American College of Cardiology 2017;69:526-37. - PMC - PubMed
Hershberger 2013
    1. Hershberger RE, Hedges DJ, Morales A. Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nature Reviews. Cardiology 2013;10(9):531-47. - PubMed
Higgins 2011
    1. Higgins JP, Deeks JJ, Altman DG. Chapter 16: Special topics in statistics. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Higgins 2017
    1. Higgins JP, Altman DG, Sterne JA. Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s), Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017). Cochrane, 2017. Available from training.cochrane.org/handbook/archive/v5.2.
Jefferies 2010
    1. Jefferies JL, Towbin JA. Dilated cardiomyopathy. Lancet 2010;375(9716):752-62. - PubMed
Jiao 2014
    1. Jiao R, Liu Y, Yang WJ, Zhu XY, Li J, Tang QZ. Effects of stem cell therapy on dilated cardiomyopathy. Saudi Medical Journal 2014;35(12):1463-8. - PMC - PubMed
Lefebvre 2011
    1. Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Liberati 2009
    1. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Medicine 2009;6(7):e1000100. - PMC - PubMed
Lu 2016
    1. Lu Y, Wang Y, Lin M, Zhou J, Wang Z, Jiang M, et al. A systematic review of randomised controlled trials examining the therapeutic effects of adult bone marrow-derived stem cells for non-ischaemic dilated cardiomyopathy. Stem Cell Research & Therapy 2016;7(1):186. - PMC - PubMed
Marquis‐Gravel 2014
    1. Marquis-Gravel G, Stevens LM, Manosur S, Avram R, Noiseux N. Stem cell therapy for the treatment of nonischemic cardiomyopathy: a systematic review of the literature and meta-analysis of randomized controlled trials. Canadian Journal of Cardiology 2014;30(11):1378-84. - PubMed
McKenna 2017
    1. McKenna WJ, Maron BJ, Thiene G. Classification, epidemiology, and global burden of cardiomyopathies. Circulation Research 2017;121:722-30. - PubMed
Menasché 2001
    1. Menasché P, Hagege AA, Scorsin M, Pouzet B, Desnos M, Duboc D, et al. Myoblast transplantation for heart failure. Lancet 2001;357(9252):279-80. - PubMed
Menasché 2018
    1. Menasché P. Cell therapy trials for heart regeneration-lessons learned and future directions. Nature Reviews. Cardiology 2018;15(11):659-71. - PubMed
Merlo 2014
    1. Merlo M, Pivetta A, Pinamonti B, Stolfo D, Zecchin M, Barbati G, et al. Long-term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: changing mortality over the last 30 years. European Journal of Heart Failure 2014;16(3):317-24. - PubMed
Merlo 2015
    1. Merlo M, Stolfo D, Anzini M, Negri F, Pinamonti B, Barbati G, et al. Persistent recovery of normal left ventricular function and dimension in idiopathic dilated cardiomyopathy during long-term follow-up: does real healing exist? Journal of the American Heart Association 2015;4(1):e001504. - PMC - PubMed
Merlo 2016
    1. Merlo M, Cannatá A, Vitagliano A, Zambon E, Lardieri G, Sinagra G. Clinical management of dilated cardiomyopathy: current knowledge and future perspectives. Expert Review of Cardiovascular Therapy 2016;14(2):137-40. - PubMed
Patel 2015
    1. Patel AN, Mittal S, Turan G, Winters AA, Henry TD, Ince H, et al. REVIVE trial: retrograde delivery of autologous bone marrow in patients with heart failure. Stem Cells Translational Medicine 2015;4(9):1021-7. - PMC - PubMed
Pinto 2016
    1. Pinto YM, Elliot PM, Arbustini E, Adler Y, Anastasakis A, Böhm M, et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. European Heart Journal 2016;37(23):1850-8. - PubMed
Poglagen 2018
    1. Poglajen G, Zemljič G, Frljak S, Cerar A, Andročec V, Sever M, et al. Stem cell therapy in patients with chronic nonischemic heart failure. Stem Cells International 2018;2018:6487812. - PMC - PubMed
Ponikowski 2016
    1. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal 2016;37:2129-200. - PubMed
Psaltis 2010
    1. Psaltis PJ, Zannettino AC, Gronthos S, Worthley SG. Intramyocardial navigation and mapping for stem cell delivery. Journal of Cardiovascular Translational Research 2010;3:135-46. - PubMed
R [Computer program]
    1. R Foundation for Statistical Computing R: a language and environment for statistical computing. Version 3.4.2. Vienna, Austria: R Foundation for Statistical Computing, 2017. Available at www.R-project.org.
Review Manager 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rong 2019
    1. Rong SL, Wang ZK, Zhou XD, Wang XL, Yang ZM, Li B. Efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy: a systematic appraisal and meta-analysis. Journal of Translational Medicine 2019;17(1):221. - PMC - PubMed
Schulz 2010
    1. Schulz KF, Altman DG, Moher D. CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c332. - PMC - PubMed
Schünemann 2017
    1. Schünemann HJ, Oxman AD, Vist GE, Higgins JP, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s), Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017). Cochrane, 2017. Available from training.cochrane.org/handbook/archive/v5.2.
Stamm 2003
    1. Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 2003;361:45-6. - PubMed
Stehlik 2011
    1. Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, et al. The registry of the International Society of Heart and Lung Transplantation: twenty-eight adult heart transplantation report. Journal of Heart and Lung Transplantation 2011;30(10):1078-94. - PubMed
Strauer 2002
    1. Strauer BE, Brehm M, Zeus T, Köstering M, Hernadez A, Sorg RV, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002;106:1913-8. - PubMed
Terzic 2016
    1. Terzic A, Behfar A. CardioPulse: regenerative medicine in the practice of cardiology. European Heart Journal 2016;37(14):1089-90. - PubMed
Terzic 2017
    1. Terzic A, Behfar A. Posology for regenerative therapy. Circulation Research 2017;121(11):1213-5. - PMC - PubMed
Vrtovec 2013
    1. Vrtovec B, Poglajen G, Lezaic L, Sever M, Domanovic D, Cernelc P, et al. Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circulation Research 2013;112:165-73. - PubMed
Vrtovec 2018a
    1. Vrtovec B. Cell therapy for nonischemic cardiomyopathy: current status and future perspectives. Circulation Research 2018;5(122):28-30. - PubMed
Vrtovec 2018b
    1. Vrtovec B, Poglajen G, Sever M, Zemljic G, Frljak S, Cerar A, et al. Effects of repetitive transendocardial CD34(+) cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation Research 2018;123:389-96. - PubMed
Weintraub 2017
    1. Weintraub RG, Semsarian C, Macdonald P. Dilated cardiomyopathy. Lancet 2017;390(10092):400-41. - PubMed
Wen 2018
    1. Wen Y, Ding J, Zhang B, Gao Q. Bone marrow-derived mononuclear cell therapy for nonischaemic dilated cardiomyopathy. A meta-analysis. European Journal of Clinical Investigation 2018;48(4):e12894. - PubMed
WHO/ISFC 1980
    1. World Health Organization/International Society and Federation of Cardiology. Report of the WHO/ISFC task force on the definition and classification of cardiomyopathies. British Heart Journal 1980;44(6):672-3. - PMC - PubMed
Yamada 2020
    1. Yamada S, Arrell DK, Rosenow CS, Bartunek J, Behfar A, Terzic A. Ventricular remodeling in ischemic heart failure stratifies responders to stem cell therapy. Stem Cells Translational Medicine 2020;9(1):74-9. - PMC - PubMed
Yancy 2013
    1. Yancy C, Jessup M, Bozkurt B, Butler J, Casey D, Drazner M, et al. ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013;128(16):e240-27. - PubMed

References to other published versions of this review

Diaz‐Navarro 2019
    1. Diaz-Navarro R, Urrútia G, Cleland JG, Poloni D, Villagran F, Bangdiwala S, et al. Stem cell therapy for dilated cardiomyopathy. Cochrane Database of Systematic Reviews 2019, Issue 9. Art. No: CD013433. [DOI: 10.1002/14651858.CD013433] - DOI - PMC - PubMed

Publication types

MeSH terms

Substances