Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine

Table 2

Completed clinical trials that evaluated the safety, efficacy, and feasibility of stem cell therapy.

Type of stem cell	Treated disease	Trial design	Number of cells	Route of administration	Outcomes	References
Pluripotent stem cells	Ischemic heart disease	An open label, phase I study to assess both the feasibility and safety of epicardial delivery of a fibrin gel embedded with human embryonic stem cell- (ESC-) derived CD15+ IsI-1+ progenitors	NA	Epicardial transplantation of cells embedded in fibrin patch	Not yet available	NCT02057900
	Advanced Stargardt’s macular dystrophy	A follow-up of a phase I/II, open-label, nonrandomized, 4-cohort, dose escalation, multicenter clinical trial to evaluate the long-term safety and tolerability of human ESC-derived retinal pigment epithelium (hESC-RPE) cellular therapy	to hESC-RPE/kg	Subretinal injection	Not yet available	NCT02941991
	Stargardt’s macular dystrophy	A phase I/II, open-label, nonrandomized, sequential, multicenter clinical trial to evaluate the safety and tolerability of hESC-RPE cellular therapy in patients with SMD and to evaluate potential efficacy endpoints to be used in future studies of hESC-RPE cellular therapy	to hESC-RPE/kg	Subretinal injection	Not yet available	NCT01469832
	Outer retinal degenerations	A phase I/II, open label, nonrandomized, prospective study to determine the safety of hESC-RPE subretinal injection	hESC- RPE/kg	Subretinal injection	Not yet available	NCT02903576
	Stargardt’s macular dystrophy	A phase I/II, open-label, nonrandomized clinical trial to evaluate the safety and tolerability of subretinal injection of hESC-RPE	to hESC-RPE/kg	Subretinal injection	Not yet available	NCT01345006
	Age-related macular degeneration	A phase I/II, open-label, nonrandomized, sequential, multicenter clinical trial to evaluate the safety and tolerability of subretinal injection of hESC-RPE	to hESC-RPE/kg	Subretinal injection	Not yet available	NCT01344993
	Age-related macular degeneration	A phase I/II trial, open-label, nonrandomized study to evaluate the long-term safety and tolerability of MA09-hRPE cellular therapy in patients with advanced dry age-related macular degeneration from one to five years following the surgical procedure to implant the MA09-hRPE cells	to hESC-RPE/kg	Subretinal injection	Not yet available	NCT02463344
	Advanced Stargardt’s macular dystrophy	A phase I/II trial, open-label, nonrandomized study to evaluate the long-term MA09-hRPE cellular therapy in patients with advanced Stargardt’s macular dystrophy from one to five years following the surgical procedure to implant the MA09-hRPE cells	to hESC-RPE/kg	Subretinal injection	Not yet available	NCT02445612
Multipotent stem cells	Diabetic peripheral neuropathy	A phase II study to investigate the effects of mesenchymal stem cell (MSC) transfusion	NA	Intravenous infusion	Not yet available	NCT02387749
	Idiopathic pulmonary fibrosis	A phase 1b study to evaluate the safety and feasibility, particularly with respect to adverse acute hemodynamic effects and profibrosis of MSC treatment	or hMSCs/kg	Intravenous infusion	Feasible and satisfactory short-term safety profile.	[141]; NCT01385644
	Acute respiratory distress syndrome	A phase 1 clinical trial to test the safety of a single dose of allogeneic bone marrow-derived MSCs (BMSCs)	, , or of hMSCs/kg	Intravenous infusion	Safe and well tolerated	[142]; NCT01775774
	Periapical periodontitis	A randomized, controlled phase I/II clinical trial to evaluate the safety and efficacy of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) encapsulated in a plasma-derived biomaterial for regenerative endodontic procedures in mature permanent teeth with apical lesions	cells/biomaterial	Encapsulated in platelet poor plasma	Safe and effective	[143]; NCT03102879
	Cleft lip and palate	A phase I trial to evaluate the feasibility and safety of deciduous dental pulp stem cells	cells/biomaterial	Embedded in hydroxyapatite-collagen sponge	Feasible and safe	[144]; NCT01932164
	Knee osteoarthritis	A multicentre, phase I/II clinical trial to evaluate the clinical use of allogenic BMSCs	cells/kg	Intra-articular injection	Feasible and safe	[145]; NCT01586312
	Knee osteoarthritis	A phase 2 study to determine the clinical response to autologous bone marrow aspirate concentrate and platelet-rich plasma injection	NA	Intra-articular injection	Not yet published	NCT02958267
	Frailty	A phase I/II randomized, double-blind, placebo-controlled clinical trial to evaluate the safety of MSC therapy	cells/kg	Intravenous infusion	Safe	[146]; NCT02065245
	Retinal degeneration	A phase 1 study to report electroretinographic (ERG) findings in advanced glaucoma treated with a single intravitreal injection of BMSCs	cells/kg	Intravitreal injection	Not yet available	NCT02330978
	Spinal cord injury	A phase I/II study to evaluate the safety and efficacy of intrathecal administration of allogeneic UC-MSCs to patients with spinal cord injury	cells/kg	Intrathecal injection	Not yet available	NCT02481440
	Knee osteoarthritis	A phase I/II study to evaluate the feasibility and safety of the implantation of 40 million BMSCs in knees with osteoarthritis of grade II-IV (Kellgren and Lawrence)	cells/kg	Intra-articular injection	Not yet available	NCT01183728
	Chronic ischemic cardiomyopathy	A phase II trial to assess the feasibility, safety, and efficacy of trans-endocardial administration of autologous MSCs and cardiac progenitor cells (CPCs), alone, and in combination	cells/kg b.w.	Trans-endocardial injection	Feasible, safe, and effective	[147]; NCT02501811
	Cardiomyopathy	A phase I study to examine the safety and feasibility of allogeneic human MSCs by trans-endocardial injection to cancer survivors	cells/kg	Trans-endocardial injection	Safe and feasible	[148]; NCT02509156
	Ischemic cardiomyopathy	A phase 1/2 randomized comparison study to test whether allogeneic MSCs are as safe and effective as autologous MSCs	, , or cells/kg	Trans-endocardial injection	Safe and effective	[149]; NCT01087996
	Nonischemic dilated cardiomyopathy	A phase I/II study to assess the safety of autologous and allogeneic human MSC administration	cells/kg	Trans-endocardial injection	Safe	[150]; NCT01392625
	Myocardial infarction	A phase II trial to compare the safety and efficacy of 2 doses of allogeneic BMSCs	or cells/kg	Trans-endocardial injection	Safe	[151]; NCT02013674
	Ischemic cardiomyopathy	A phase I/II study to demonstrate the safety of trans-endocardial injection of autologous MSCs and bone marrow mononuclear cells	or cells/kg	Trans-endocardial injection	Safe	[152]; NCT00768066
	End-stage liver disease	A phase I/II study to investigate the feasibility, safety, and efficacy of autologous MSC injection	MSCs	Peripheral or portal vein injection	Feasible, safe, and effective	[153]; NCT01440309
	Knee osteoarthritis	A randomized, phase 2b study to assess the efficacy and safety of a single intra-articular injection of adipose tissue-derived MSCs (AT-MSCs)	MSCs	Intra-articular injection	Safe and effective with satisfactory functional improvement and pain relief in patients	[154]
	Heart failure	A phase 1/2 randomized controlled trial to evaluate the safety and efficacy of the intravenous infusion of UC-MSCs in patients with chronic stable heart failure and reduced ejection fraction	MSCs/kg	NA	Safe and effective with improvement in quality of life	[155]; NCT01739777
	COVID-19	A phase 1 clinical trial to evaluate the safety of human UC-MSC infusion in the treatment of patients with moderate and severe COVID-19 pulmonary disease	of UC-MSCs	NA	Safe and well tolerated without serious adverse events	[140]

NA: not available.