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.
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.
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DOI：
10.1002/ejhf.2178
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发表时间：
2021-04
影响因子：
18.2
通讯作者：
Cardiovascular Cell Therapy Research Network (CCTRN)
中科院分区：
文献类型：
--
作者：
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)
Concert-HF是一项由NHLBI赞助的、双盲、安慰剂对照的II期试验，旨在确定单独或联合使用自体骨髓间充质干细胞(MSCs)和c-kit阳性心肌细胞(CPC)治疗缺血性心肌病引起的心力衰竭(HF)是否可行、安全和有益。患者被随机(1：1：1：1)接受经心内膜注射间充质干细胞联合CPC、单独注射MSCs、单独注射CPC或安慰剂，并随访12个月。7个中心招募了125名参与者，左心室射血分数为28.6±6.1%，疤痕大小为19.4±5.8%，均为纽约心脏协会II级或III级。仅服用−的主要不良心脏事件(MACE)的比例显著降低(CPCS与安慰剂相比，P=0.043)。与安慰剂相比，单独使用MSCs(P=0.050)和MSCs+CPC(P=0.023)显著改善了生活质量(明尼苏达州心力衰竭患者问卷得分)。两组间的左心室射血分数、左心室容量、疤痕大小、6分钟步行距离和最大耗氧量无显著差异。这是第一个评估心衰患者不同组织中的CPC和两种细胞类型的组合的多中心试验。结果表明，治疗是安全可行的。即使在最大限度地指导治疗的情况下，CPC和MSCs都与缺血性心力衰竭的临床结果(分别为MACE和生活质量)的改善有关，而不影响左心功能或结构，这表明可能的全身或旁分泌细胞机制。骨髓间充质干细胞和CPC的结合与这两种结果的改善有关。这些结果提示了CPC和MSCs潜在的重要益处，并支持了对心力衰竭患者的进一步研究。心血管细胞治疗研究网络：CONTACT-HF试验。Constant-HF是第一个评估心力衰竭(HF)患者c-kit阳性心肌细胞(CPC)和来自不同组织的两种细胞类型组合的多中心试验。在慢性缺血性心力衰竭患者中应用自体CPC或间充质基质细胞(MSCs)显示了良好的效果，即在接下来的12个月中，分别减少了因心力衰竭的住院时间和改善了生活质量。这项II期研究的结果为细胞疗法治疗慢性缺血性心力衰竭的其他临床试验提供了理论基础。
CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy. Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (−22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups. This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients. Cardiovascular Cell Therapy Research Network: the CONCERT-HF trial. CONCERT-HF is the first multicentre trial assessing c-kit positive cardiac cells (CPCs) and a combination of two cell types from different tissues in heart failure (HF) patients. Administration of autologous CPCs or mesenchymal stromal cells (MSCs) in patients with chronic ischaemic HF shows promising effects, namely, a reduction in hospitalization for HF and an improvement in quality of life, respectively, over the ensuing 12 months. Results of this Phase II study provide a rationale for additional clinical trials of cell therapy in chronic ischaemic HF.
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影响因子：
120.7
作者：
Heldman, Alan W.;DiFede, Darcy L.;Fishman, Joel E.;Zambrano, Juan P.;Trachtenberg, Barry H.;Karantalis, Vasileios;Mushtaq, Muzammil;Williams, Adam R.;Suncion, Viky Y.;McNiece, Ian K.;Ghersin, Eduard;Soto, Victor;Lopera, Gustavo;Miki, Roberto;Willens, Howard;Hendel, Robert;Mitrani, Raul;Pattany, Pradip;Feigenbaum, Gary;Oskouei, Behzad;Byrnes, John;Lowery, Maureen H.;Sierra, Julio;Pujol, Mariesty V.;Delgado, Cindy;Gonzalez, Phillip J.;Rodriguez, Jose E.;Bagno, Luiza Lima;Rouy, Didier;Altman, Peter;Foo, Cheryl Wong Po;da Silva, Jose;Anderson, Erica;Schwarz, Richard;Mendizabal, Adam;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
24
作者：
Hare, Joshua M.;Traverse, Jay H.;Henry, Timothy D.;Dib, Nabil;Strumpf, Robert K.;Schulman, Steven P.;Gerstenblith, Gary;DeMaria, Anthony N.;Denktas, Ali E.;Gammon, Roger S.;Hermiller, James B., Jr.;Reisman, Mark A.;Schaer, Gary L.;Sherman, Warren
通讯作者：
Sherman, Warren
影响因子：
20.1
作者：
Karantalis V;DiFede DL;Gerstenblith G;Pham S;Symes J;Zambrano JP;Fishman J;Pattany P;McNiece I;Conte J;Schulman S;Wu K;Shah A;Breton E;Davis-Sproul J;Schwarz R;Feigenbaum G;Mushtaq M;Suncion VY;Lardo AC;Borrello I;Mendizabal A;Karas TZ;Byrnes J;Lowery M;Heldman AW;Hare JM
通讯作者：
Hare JM
影响因子：
20.1
作者：
Hatzistergos KE;Quevedo H;Oskouei BN;Hu Q;Feigenbaum GS;Margitich IS;Mazhari R;Boyle AJ;Zambrano JP;Rodriguez JE;Dulce R;Pattany PM;Valdes D;Revilla C;Heldman AW;McNiece I;Hare JM
通讯作者：
Hare JM
影响因子：
168.9
作者：
Patel, Amit N.;Henry, Timothy D.;DeMaria, Anthony
通讯作者：
DeMaria, Anthony