Wharton’s jelly mesenchymal stem cells: Future regenerative medicine for clinical applications in mitigation of radiation injury

Table 1 Different types of stem cells and their characteristics

Characteristics	Embryonic stem cells	Induced pluripotent stem cells	Adult stem cells	Ref.
Origin	Inner cell mass of blastocyst	Somatic cells	Postnatal adult tissue	[16]
Potency	Pluripotent	Pluripotent	Multipotent	[17]
Self-renewal	Yes	Yes	Limited	[17]
Teratoma formation	Yes	Yes	No	[18]
Tumorigenesis	Yes	Yes	No	[18]
Immune response	Immuno-privileged MHC-I and II present in low level	Not immuno-privileged MHC-I and II present in normal level	MSCs are immuno-privileged and immunosuppressive in nature	[18,19,20,21,22]
Ethical issue	Serious ethical issue	No ethical issue	No ethical issue	[21]

MHC: Major histocompatibility class; MSC: Mesenchymal stem cell.

Table 2 Characteristic feature of major mesenchymal stem cells

Characteristics	BM-MSCs	AD-MSCs	UC-MSCs	Ref.
Harvesting procedure	Invasive	Invasive	Non-invasive	[18]
Potency to differentiate	Low	Low	High	[18,20]
Proliferative potential	Low	Low	High	[18,20,21]
Immune modulatory properties	Good	Good	Good	[18]
Allogenic cell rejection	No	No	No	[18,22]
Ethical issue	No	No	No	[23]
Risk of tumorigenicity	No	No	No	[18]

BM-MSC: Bone marrow mesenchymal stem cell; AD-MSC: Adipose-derived mesenchymal stem cell; UC-MSC: Umbilical cord mesenchymal stem cell.

Table 3 List of clinical trials using Wharton’s jelly mesenchymal stem cells for it therapeutic applications

No.	Study title	Clinical trial code numbers	Conditions	Status/conclusions
1	Randomized study of coronary revascularization surgery with injection of WJ-MSCs and placement of an epicardial extracellular matrix	NCT04011059	Cardiovascular diseases: Heart failure, coronary artery disease	Not yet recruiting
			Mesenchymal stem cell transplantation, regenerative medicine
2	MSCs for prevention of MI-induced HF	NCT05043610	Myocardial infarction: Acute, anterior wall	Recruiting
			Cardiac remodeling, ventricular
			STEMI, regenerative medicine
			Heart failure
3	The application of the umbilical cord mesenchymal stem cells in the complex treatment of non-ischemic heart failure	NCT04325594	Chronic heart failure	Completed. Result not available
			Non-ischemic cardiomyopathy, dilated cardiomyopathy
4	Treatment of degenerative disc disease with allogenic mesenchymal stem cells (MSV)	NCT01860417	Degenerative disc disease	Completed. Result available. But not concluded yet
			Intervertebral disc disease
			Low back pain
5	Treatment of knee osteoarthritis with allogenic mesenchymal stem cells	NCT01586312	Arthritis of knee	Completed. Result available. But not concluded yet
6	Ultrasound-guided treatments for shoulder pain in wheelchair users with spinal cord injury	NCT04136743	Spinal cord injuries	Recruiting
			Tendinopathy
			Rotator cuff tears
			Shoulder pain
7	Ultrasound-guided injections for meniscal injuries in active-duty military	NCT04274543	Tibial meniscus injuries	Recruiting
			Knee injuries and disorders
8	3D tissue engineered bone equivalent for treatment of traumatic bone defects	NCT03103295	Bone defects	Unknown status
9	Safety and feasibility study of the CELLSPAN esophageal implant (CEI) in patients requiring short segment esophageal replacement	NCT05877300	Esophageal diseases	Not yet recruiting
10	Micro-fragmented adipose tissue and complex Crohns’ anal fistulas	NCT03555773	Crohn disease, perianal fistula	Completed. Result not available
11	Micro-fragmented adipose Tissue (Lipogems®) injection for chronic shoulder pain in persons with spinal cord injury	NCT03167138	Shoulder pain	Unknown status
			Shoulder impingement syndrome
			Rotator cuff impingement syndrome, rotator cuff tendinitis, rotator cuff syndrome of shoulder and allied disorders
			Spinal cord injuries
12	Encapsulated mesenchymal stem cells for dental pulp regeneration	NCT03102879	Periapical periodontitis	Completed. Result available. But no conclusion
13	Allogeneic cord blood cells for adults with severe acute contusion spinal cord injury	NCT04331405	Spinal cord contusion	Completed. Result not available
14	Wharton’s jelly-derived mesenchymal stem cells in osteoarthritis	NCT03866330	Osteoarthritis: Hip, knee, glenohumeral	Unknown status
15	Cardiovascular clinical project to evaluate the regenerative capacity of cardiocell in patients with acute myocardial infarction (AMI)	NCT03404063	Myocardial infarction	Completed. Result not available
16	Randomized clinical trial to evaluate the regenerative capacity of cardiocell in patients with chronic ischaemic heart failure (CIHF)	NCT03418233	Heart failure	Completed. Result not available
17	Cardiovascular clinical project to evaluate the regenerative capacity of cardiocell in patients with no-option critical limb ischemia (N-O CLI)	NCT03423732	Critical limb ischemia	Unknown status
18	Transplantation of allogeneic MSC in patients with pulp necrosis and chronic apical periodontitis	NCT04545307	Pulp Necroses|Apical Periodontitis	Completed. Result not available
19	Efficacy of intradiscal injection of autologous bm-MSC in subjects with chronic LBP due to multilevel lumbar IDD	NCT05066334	Intervertebral Disc Degeneration|Chronic Low-back pain	Recruiting
20	Allogeneic ADSCs and platelet-poor plasma fibrin hydrogel to treat the patients with burn wounds (ADSCs-BWs)	NCT03113747	Second- or third-degree burns	Unknown status
21	Allogeneic mesenchymal stromal cells in elderly patients with hip fracture	NCT02630836	Femoral neck fracture	Withdrawn
22	Umbilical cord blood-derived mesenchymal stem cells in regeneration of sweat glands and body repair	NCT02304562	Sweat gland diseases	Unknown status
23	Residual dental pulp tissue and cord blood stem cells	NCT04040127	Irreversible pulpitis	Withdrawn
24	Treatment of osteoarthritic knee with high tibial osteotomy and implantation of allogenic human umbilical cord blood-derived stem cells	NCT04234412	Osteoarthritis, knee	Unknown status
25	Umbilical cord blood collection and processing for hypoplastic left heart syndrome patients	NCT01856049	Hypoplastic left heart syndrome	Recruiting
26	Stem cell educator therapy in type 1 diabetes	NCT03390231	Type 1 diabetes	Unknown status
27	Use of Wharton Jelly in diabetic nephropathy	NCT03288571	Diabetic nephropathies	Not yet recruiting
28	Efficacy of Wharton jelly in erectile dysfunction	NCT03751735	Erectile dysfunction associated with type 2 diabetes mellitus	Completed. Result not available
29	Safety of Wharton Jelly in erectile dysfunction	NCT02945449	Erectile dysfunction associated with type 2 diabetes mellitus	Completed. Result not available
30	Treatment of COVID-19 patients using Wharton’s jelly-mesenchymal stem cells	NCT04313322	Use of stem cells for COVID-19 treatment	Recruiting
31	Use of mesenchymal stem cells in inflammatory bowel disease	NCT03299413	Inflammatory bowel diseases	Active, not recruiting
32	Intrathecal administration of expanded Wharton’s jelly mesenchymal stem cells in chronic traumatic spinal cord injury	NCT03003364	Spinal cord injury, chronic	Completed. Result not available
33	Evaluation of umbilical cord-derived Wharton’s jelly stem cells for the treatment of acute graft versus host disease	NCT03158896	Acute graft versus host disease	Active, not recruiting
34	Use of Wharton Jelly-derived mesenchymal stem cells for knee osteoarthrosis	NCT02963727	Knee osteoarthrosis	Recruiting
35	Management of retinitis pigmentosa by Wharton’s jelly-derived mesenchymal stem cells	SHGM56733164	Retinitis pigmentosa	Completed. Result not available
			Inherited retinal dystrophy
36	Safety and efficacy of intravenous Wharton’s jelly-derived mesenchymal stem cells in acute respiratory distress syndrome due to COVID-19	NCT04625738	Acute respiratory distress syndrome	Not yet recruiting
37	Wharton’s jelly-derived mesenchymal stem cells in osteoarthritis	NCT03866330	Osteoarthritis: Hip, knee, glenohumeral	Recruiting
38	Intracoronary human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) transfer in patients with acute myocardial infarction (AMI)	NCT01291329	ST-elevation myocardial infarction	Completed. Result not available
39	Therapeutic potential of stem cell conditioned medium on chronic ulcer wounds	NCT04134676	Chronic ulcer	Not yet recruiting
40	Effect of implanting allogenic cytokines derived from human amniotic membrane (HAM) and mesenchymal stem cells derived from human umbilical cord Wharton’s jelly (HUMCWJ) on pain and functioning of knee osteoarthritis	NCT03337243	Knee osteoarthritis	Completed. Result not available
			Knee pain chronic
			Joint disease
			Musculoskeletal disease
41	Intracoronary or intravenous infusion human Wharton’s jelly-derived mesenchymal stem cells in patients with ischemic cardiomyopathy	NCT02368587	Ischemic cardiomyopathy	Not yet recruiting
42	Therapeutic treatment of amyotrophic lateral sclerosis	NCT02881476	Amyotrophic lateral sclerosis	Unknown
43	Pericardial matrix with mesenchymal stem cells for the treatment of patients with infarcted myocardial tissue	NCT03798353	Myocardial infarction	Recruiting
44	A research study looking at specific tissue of the umbilical cord	NCT01166776	Varices of umbilical cord	Completed. Result not available
45	Efficacy and safety evaluation of mesenchymal stem cells for the treatment of patients with respiratory distress due to COVID-19	NCT04390139	COVID-19, SARS-CoV-2	Recruiting
			Adult respiratory distress syndrome
46	Treatment of spinal cord injuries with (AutoBM-MSCs) versus (WJ-MSCs)	NCT04288934	Spinal cord injuries	Recruiting
47	Cell therapy using umbilical cord-derived mesenchymal stromal cells in SARS-CoV-2-related ARDS	NCT04333368	SARS-CoV-2	Recruiting
			Severe acute respiratory distress syndrome
48	Role of stem cells in improving implantation rates in ICSI patients	NCT01649752	Assess the efficacy of differentiated and undifferentiated stem cell therapy in improving endometrial receptivity	Unknown
49	Wharton’s jelly-derived mesenchymal stromal cell repeated treatment of adult patients diagnosed with type I diabetes	NCT03973827	Type 1 diabetes	Recruiting

WJ-MSCs: Wharton’s jelly mesenchymal stem cells; MSC: Mesenchymal stem cell; MI: Myocardial infarction; HF: Heart failure; CEI: CELLSPAN esophageal implant; AMI: Acute myocardial infarction; CHF: Chronic heart failure; CLI: Critical limb ischemia; BM-MSC: Bone marrow mesenchymal stem cell; LBP: Low back pain; IDD: Intervertebral disc degeneration; ADSC: Adipose-derived stem cell; ADSC-BW: Adipose-derived stem cell-burn wound; COVID-19: Coronavirus disease 2019; HAM: Human amniotic membrane; HUMCWJ: Human umbilical cord Wharton’s jelly; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; ICSI: Intracytoplasmic sperm injection.