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.
| Original language | English |
|---|---|
| Article number | 235 |
| Journal | Stem Cell Research and Therapy |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Sep 14 2018 |
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ASJC Scopus subject areas
- Medicine (miscellaneous)
- Molecular Medicine
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Cell Biology
Cite this
Linking cell function with perfusion : Insights from the transcatheter delivery of bone marrow-derived CD133+ cells in ischemic refractory cardiomyopathy trial (RECARDIO) 11 Medical and Health Sciences 1103 Clinical Sciences 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology. / Bassetti, Beatrice; Carbucicchio, Corrado; Catto, Valentina; Gambini, Elisa; Rurali, Erica; Bestetti, Alberto; Gaipa, Giuseppe; Belotti, Daniela; Celeste, Fabrizio; Parma, Matteo; Righetti, Stefano; Biava, Lorenza; Arosio, Maurizio; Bonomi, Alice; Agostoni, Piergiuseppe; Scacciatella, Paolo; Achilli, Felice; Pompilio, Giulio.
In: Stem Cell Research and Therapy, Vol. 9, No. 1, 235, 14.09.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Linking cell function with perfusion
T2 - Insights from the transcatheter delivery of bone marrow-derived CD133+ cells in ischemic refractory cardiomyopathy trial (RECARDIO) 11 Medical and Health Sciences 1103 Clinical Sciences 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology
AU - Bassetti, Beatrice
AU - Carbucicchio, Corrado
AU - Catto, Valentina
AU - Gambini, Elisa
AU - Rurali, Erica
AU - Bestetti, Alberto
AU - Gaipa, Giuseppe
AU - Belotti, Daniela
AU - Celeste, Fabrizio
AU - Parma, Matteo
AU - Righetti, Stefano
AU - Biava, Lorenza
AU - Arosio, Maurizio
AU - Bonomi, Alice
AU - Agostoni, Piergiuseppe
AU - Scacciatella, Paolo
AU - Achilli, Felice
AU - Pompilio, Giulio
PY - 2018/9/14
Y1 - 2018/9/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85053351576&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053351576&partnerID=8YFLogxK
U2 - 10.1186/s13287-018-0969-z
DO - 10.1186/s13287-018-0969-z
M3 - Article
AN - SCOPUS:85053351576
VL - 9
JO - Stem Cell Research and Therapy
JF - Stem Cell Research and Therapy
SN - 1757-6512
IS - 1
M1 - 235
ER -