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Stem Cell Res Ther. 2018 Sep 14;9(1):235. doi: 10.1186/s13287-018-0969-z.

Linking cell function with perfusion: insights from the transcatheter delivery of bone marrow-derived CD133+ cells in ischemic refractory cardiomyopathy trial (RECARDIO).

Author information

1
Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS, Via Carlo Parea 4, 20138, Milan, Italy.
2
Heart Rhythm Center, Centro Cardiologico Monzino-IRCCS, Via Carlo Parea 4, 20138, Milan, Italy.
3
Service of Nuclear Medicine, IRCCS Multimedica, Via Milanese 300, 20099, Sesto San Giovanni, Milan, Italy.
4
Laboratory of Cell and Gene Therapy "Stefano Verri", ASST-Monza, San Gerardo Hospital, Via Pergolesi 33, 20900, Monza, Italy.
5
Tettamanti Research Center, Tettamanti Foundation, Via Pergolesi 33, 20900, Monza, Italy.
6
University of Milano Bicocca, Via Pergolesi 33, 20900, Monza, Italy.
7
Cardiovascular Imaging Area, Centro Cardiologico Monzino-IRCCS, Via Carlo Parea 4, 20138, Milan, Italy.
8
Haematology Division and BMT Unit, ASST-Monza, San Gerardo Hospital, Via Pergolesi 33, 20900, Monza, Italy.
9
Department of Cardiology, ASST-Monza, San Gerardo Hospital, Via Pergolesi 33, 20900, Monza, Italy.
10
Department of Cardiovascular and Thoracic Diseases, Città della Salute e della Scienza Hospital, Corso Bramante 88, 10126, Turin, Italy.
11
Nuclear Medicine Unit, ASST-Monza, San Gerardo Hospital and University of Milano Bicocca, Via Pergolesi, 33, 20900, Monza, Italy.
12
BioStatistical Unit, Centro Cardiologico Monzino-IRCCS, Via Carlo Parea 4, 20138, Milan, Italy.
13
Heart Failure, Clinical Cardiology and Rehabilitation Cardiology Unit, Centro Cardiologico Monzino-IRCCS, Via Carlo Parea 4, 20138, Milan, Italy.
14
Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Via Festa del Perdono 7, 20122, Milan, Italy.
15
Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS, Via Carlo Parea 4, 20138, Milan, Italy. giulio.pompilio@ccfm.it.
16
Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Via Festa del Perdono 7, 20122, Milan, Italy. giulio.pompilio@ccfm.it.

Abstract

BACKGROUND:

Cell therapy with bone marrow (BM)-derived progenitors has emerged as a promising therapeutic for refractory angina (RA) patients. In the present study, we evaluated the safety and preliminary efficacy of transcatheter delivery of autologous BM-derived advanced therapy medicinal product CD133+ cells (ATMP-CD133) in RA patients, correlating perfusion outcome with cell function.

METHODS:

In the phase I "Endocavitary Injection of Bone Marrow Derived CD133+ Cells in Ischemic Refractory Cardiomyopathy" (RECARDIO) trial, a total of 10 patients with left ventricular (LV) dysfunction (ejection fraction ≤ 45%) and evidence of reversible ischemia, as assessed by single-photon emission computed tomography (SPECT), underwent BM aspiration and fluoroscopy-based percutaneous endomyocardial delivery of ATMP-CD133. Patients were evaluated at 6 and 12 months for safety and preliminary efficacy endpoints. ATMP-CD133 samples were used for in vitro correlations.

RESULTS:

Patients were treated safely with a mean number of 6.57 ± 3.45 ×  106 ATMP-CD133. At 6-month follow-up, myocardial perfusion at SPECT was significantly ameliorated in terms of changes in summed stress (from 18.2 ± 8.6 to 13.8 ± 7.8, p = 0.05) and difference scores (from 12.0 ± 5.3 to 6.1 ± 4.0, p = 0.02) and number of segments with inducible ischemia (from 7.3 ± 2.2 to 4.0 ± 2.7, p = 0.003). Similarly, Canadian Cardiovascular Society and New York Heart Association classes significantly improved at follow-up vs baseline (p ≤ 0.001 and p = 0.007, respectively). Changes in summed stress score changes positively correlated with ATMP-CD133 release of proangiogenic cytokines HGF and PDGF-bb (r = 0.80, p = 0.009 and r = 0.77, p = 0.01, respectively) and negatively with the proinflammatory cytokines RANTES (r = - 0.79, p = 0.01) and IL-6 (r = - 0.76, p = 0.02).

CONCLUSION:

Results of the RECARDIO trial suggested safety and efficacy in terms of clinical and perfusion outcomes in patients with RA and LV dysfunction. The observed link between myocardial perfusion improvements and ATMP-CD133 secretome may represent a proof of concept for further mechanistic investigations.

TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02059681 . Registered 11 February 2014.

PMID:
30217223
PMCID:
PMC6137884
DOI:
10.1186/s13287-018-0969-z
[Indexed for MEDLINE]
Free PMC Article

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