Clinical cardiac regenerative studies in children

Table 1 Pediatric cardiac diseases treated with cells

Cell-based cardiac regenerative treatment	Ongoing studies
Dilated cardiomyopathy (Dil. CMP)	Dilated cardiomyopathy (Dil. CMP)
Idiopathic dilated CMP
Cytostatics-induced dilated CMP
Postmyocarditis dilated CMP
Ischemic heart failure (myocardial infarction)
Anomalous origin of the left coronary arteries
Takayasu arteritis
Congenital heart disease
DORV after surgical correction
Pulmonary atresia with ventricular septal defect
HLHS	Hypoplastic left heart syndrome (HLHS)

CMP: Cardiomyopathy; DORV: Double outlet right ventricle; HLHS: Hypoplastic left heart syndrome.

Table 2 Published clinical studies with pediatric cell-based cardiac regeneration

Ref.	Study type	Diagnosis	No. of children	Mean age of children (m)	Sex	Type of stem cell	Cell application	FUP	Main results
Lacis et al[30]	Case report	Dil. CMP	1	3.5 mo	F	BM-MNC	IM	4 mo	LV EF from 20% to 41%
Rupp et al[31]	Case report	Dil. CMP	9	4 mo-16 yr	NA	BM-MNCs	IC	1-52 mo	3 patients HTX, 1 patient died, others improved
Ishigami et al[32] (TICAP study)	Controlled study	HLHS	7 treated and 7 controls	< 6 yr	NA	CDCs	IC	18 mo	Increase in RV EF from 46.9% to 52.1% in treated patients
Rupp et al[33]	Case report	HLHS	1	11 mo	M	BMC	IC	14 mo	RV EF from 22% to 44%
Rupp et al[34]	Case report	Dil. CMP	1	2 year	M	BMC	IC	6 mo	EF from 24% to 45%,
									BNP and NYHA decreased
De Lezo et al[35]	Case Report	Post-AMI	1	7 mo	NA	BM-MNCs	IC	14 mo	LV EF from 20% to 43%
Olguntürk et al[36]	Case report	Dil. CMP	2	6 and 9 yr	M, F	PBSC after GCSF treatment	IC	8 wk, and 6 mo	1st patient LV EF from: 16% to 39%; 2nd patient LV EF from 34% to 54%
Limsuwan et al[37]	Case report	HF post-AMI	1	9 yr	F	BMC after GCSF treatment	IC	3 mo	LV EF form 30% to 47%
Zeinaloo et al[38]	Case report	Dil. CMP	1	11 yr	M	BM-MSC	IC	1 yr	LV EF from 20% to 42%
Rivas et al[39]	Case report	Dil. CMP	2	3 and 4 mo	M	PBSC after G-CSF treatment	IC	4 mo	EF from < 30% to > 40%
Bergmane et al[40]	Case report	Dil. CMP	7	4 mo-17 yr	NA	BMC	IM	1 yr	6 patients controlled, LV EF from 33.5% to 54%
Burkhart et al[41]	Case report	HLHS	1	3 m	NA	Umbilical cord blood derived cells	IM	3 mo	EF increased to 45%

BMC: Bone marrow cells; CDC: Cardiosphere-derived cells; BNP: Brain natriuretic peptide; HTX: Heart transplantation; NYHA: New York Heart Association Classification; GCSF: Granulocyte-colony stimulating factor; CMP: Cardiomyopathy; LV: Left ventricle; EF: Ejection fraction; BM-MNC: Bone marrow mononuclear cell; PBSC: Peripheral blood stem cell; RV: Right ventricle; IC: Intracoronary; IM: Intramyocardial; FUP: Follow-up; NA: Data not available; HLHS: Hypoplastic left heart syndrome; F: Female; M: Male.

Table 3 On-going registered clinical studies

Clinicaltrials.gov ID	Diagnosis	Intervention	Study design	No. of patients to enroll	Age eligible	Status
NCT01504594	Dilated CMP	Intracoronary autologous stem cell infusion	Single Group Assignment	10	1 to 16	Suspended
NCT02256501	CMP	Intracoronary	Randomized	32	1 to 16	Recruiting
NCT02398604	HLHS	intramyocardial injection of allogeneic mesenchymal cells during the Bi-Directional	Randomized	30	to 28 d	Study is not yet open
		Cavopulmonary Anastomosis
NCT01883076	HLHS	injections of autologous umbilical cord blood cells into the right ventricle of	Safety Study	10	< 18 mo	Recruiting
		HLHS children undergoing a scheduled Glenn surgical procedure.
NCT01829750	HLHS	efficacy of intracoronary infusion of cardiac progenitor cells in patients with univentricular heart disease	Randomized	34	< 20 yr	Recruiting

HLHS: Hypoplastic left heart syndrome; CMP: Cardiomyopathy.