Mesenchymal stem cell secretome and exosomes as potential advanced therapy medicinal products for treating a failing heart

Table 2 Clinical trials evaluating cell-free and cell-based therapies for different cardiovascular diseases

NCT & title	Condition	Intervention	Phase & sample size (n)	Country	Primary outcome parameters	ROA	Dose
Transplantation of MSCs for the prevention of AMI-induced HF. NCT05043610	Prevention of AMI-induced HF	UC-derived WJ-MSCs	Phase 3, n = 390 (completed)	Iran	The primary endpoint for assessing the intervention’s efficacy will be the incidence of HF	I/C	All 130 patients will receive a single intracoronary infusion of 107 WJ-MSCs, alongside the conventional treatment provided to the same number of patients in the control group
Exosome-based Nanoplatform for Ldlr mRNA Delivery in FH (ENDFH). NCT05043181	FH	LDLR mRNA exosomes	Phase 1, n = 30 (not yet recruiting)	China	Safety and preliminary effectiveness of exosome-based LDLR mRNA nanoplatform for gene therapy in HoFH	Abdominal puncture under ultrasound guidance	Escalation phase: Six dose groups are planned (with single doses of 0.044 mg/kg, 0.088 mg/kg, 0.145 mg/kg, 0.220 mg/kg, 0.295 mg/kg, and 0.394 mg/kg, respectively), with three treatments per group. Extension phase: 12 subjects are enrolled and receive three weekly infusions of LDLR mRNA exosomes, with the single dose determined in the dose-escalation phase
Cardiovascular Clinical Project to Evaluate the Regenerative Capacity of CardioCell in Patients with AMI. NCT03404063	AMI	CardioCell	Phase 2/3; n = 105 (completed)	Poland	Improve the clinical outcomes in patients with AMI	Coronary-non-occlusive method (CIRCULATE catheter)	Active IMP consists of 30000000 WJMSCs suspended in 20 mL 0.9% NaCl and 5% albumin administered
Safety and Efficacy of Intracoronary Adult Human Mesenchymal Stem Cells After Acute Myocardial Infarction (SEED-MSC). NCT01392105	AMI	Autologous BM-derived MSCs	Phase 2/3; n = 80 (completed)	South Korea	Safety and efficacy of intracoronary autologous BM-derived hMSCs in patients with AMI	I/C injection	Single dose of autologous BM-derived MSCs. Dosage: 1 × 1000000 cells/kg

NCT: National clinical trial; ROA: Route of administration; MSCs: Mesenchymal stem cells; AMI: Acute myocardial infarction; FH: Familial hypercholesterolemia; UC: Umbilical cord: WJ-MSCs: Wharton’s jelly-derived mesenchymal stem cells; I/C: Intracoronary; LDLR: Low-density lipoprotein receptor; HoFH: Homozygous familial hypercholesterolemia; IMP: Investigational medicinal product; BM: Bone marrow; hMSCs: Human mesenchymal stem cells.