Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial.
BACKGROUND
Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function.


OBJECTIVE
The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome.


RESULTS
Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%±4.6% to 52.1%±2.4%; P=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%±6.8% versus 40.4%±7.6%; P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007).


CONCLUSIONS
Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes.


BACKGROUND
http://www.clinicaltrials.gov. Unique identifier: NCT01273857.
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Shuta
S
Ishigami
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Shinichi
S
Ohtsuki
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Suguru
S
Tarui
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Daiki
D
Ousaka
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Takahiro
T
Eitoku
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Maiko
M
Kondo
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Michihiro
M
Okuyama
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Junko
J
Kobayashi
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Kenji
K
Baba
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Sadahiko
S
Arai
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Takuya
T
Kawabata
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Ko
K
Yoshizumi
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Atsushi
A
Tateishi
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Yosuke
Y
Kuroko
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Tatsuo
T
Iwasaki
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Shuhei
S
Sato
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Shingo
S
Kasahara
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan.
Shunji
S
Sano
From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan. hidemasa@md.okayama-u.ac.jp.
Hidemasa
H
Oh
D002675:Child, Preschool; D015150:Echocardiography, Doppler; D005240:Feasibility Studies; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D032383:Myocytes, Cardiac / Q000637:transplantation*; D010166:Palliative Care; D011446:Prospective Studies; D020127:Recovery of Function; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013318:Stroke Volume; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D016278:Ventricular Function, Right
cell therapy; congenital heart disease; hypoplastic left heart syndrome; stem cells