Clinical trials using mesenchymal stem cells in liver diseases and inflammatory bowel diseases

Tsuchiya, Atsunori; Kojima, Yuichi; Ikarashi, Shunzo; Seino, Satoshi; Watanabe, Yusuke; Kawata, Yuzo; Terai, Shuji

doi:10.1186/s41232-017-0045-6

Inflammation and Regeneration

Table 1 Clinical trials in liver diseases

From: Clinical trials using mesenchymal stem cells in liver diseases and inflammatory bowel diseases

No.	Start year	Cell source	Autologous/allogeneic	Administration route	Number of cells infused	Etiology	Number of patients	Follow-up period	Phase	Study design	ClinicalTrials.gov identifier	Status	Result	References
1	2013	Bone marrow	Autologous	Peripheral vein	Unknown	LC	20	48 weeks	Phase 1–2	Non-randomized, single group assignment, open label	NCT01877759	Unknown
2	2009	Bone marrow	Autologous	Hepatic artery	5 × 106 cells/patient, 2 times	LC (alcohol)	11	24 weeks	Phase 2	Non-randomized, single group assignment, open label	NCT01741090	Unknown	Histological improvement. Improvement in Child- Pugh score. Decrease in TGFβ1, collagen type I, and α-SMA
3	2009	Bone marrow	Autologous	Peripheral vein	1.0 × 106/kg	LC	25	24 weeks	Unknown	Non-randomized, single group assignment, open label	NCT01499459	Unknown	Improvement in Alb and MELD scores.	13
4	2014	Umbilical cord	Allogeneic	Peripheral vein	4.0 × 107/patient, 4 times	LC	320	144 weeks	Phase 1–2	Non-randomized, parallel assignment, open label	NCT01573923	Unknown
5	2016	Adipose tissue	Autologous	Portal vein or hepatic artery	1.0 × 106/kg via peripheral vein, 3 times or 3.0 × 106/kg via hepatic artery, 3 times	LC (HCV)	5	48 weeks	Phase 1–2	Non-randomized, single group assignment, open label	NCT02705742	Recruiting
6	2007	Bone marrow	Autologous	Peripheral or portal vein	30–50 × 106/patient	LC	8	24 weeks	Phase 1–2	Randomized, single group assignment, single blind	NCT00420134	Completed	Improvement in liver function and MELD scores.	14
7	2016	Bone marrow	Allogeneic	Peripheral vein	2.0 × 106/kg, 4 times	ACLF	30	96 weeks	Phase 1	Randomized, parallel assignment, double blind (subject, caregiver, investigator)	NCT02857010	Recruiting
8	2009	Umbilical cord	Allogeneic	Peripheral vein	5.0 × 105/kg, 3 times	ACLF (HBV)	43	96 weeks	Phase 1–2	Randomized, parallel assignment, double blind (subject, caregiver)	NCT01218464	Unknown	Improvement in liver function and MELD scores.	15
9	2011	Bone marrow	Allogeneic	Peripheral vein	2.0 × 105/kg, 4 times or 1.0 × 106/kg, 4 times or 5.0 × 106/kg, 4 times	Liver failure (HBV)	120	48 weeks	Phase 2	Randomized, parallel assignment, open label	NCT01322906	Unknown
10	2010	Umbilical cord	Allogeneic	Unknown	Unknown	LC	20	48 weeks	Phase 1–2	Randomized, parallel assignment, open label	NCT01342250	Completed
11	2012	Bone marrow	Allogeneic	Hepatic artery	Unknown	LC (Alcohol)	40	96 weeks	Phase 2	Randomized, parallel assignment, open label	NCT01591200	Completed
12	2012	Umbilical cord	Allogeneic	Peripheral vein	1.0 × 105/kg, 4 times	Liver failure (HBV)	120	48 weeks	Phase 1–2	Randomized, parallel assignment, open label	NCT01724398	Unknown
13	2016	Bone marrow	Autologous	Portal vein	2.0 × 106/kg	LC	40	24 weeks	Phase 1–2	Non-randomized, parallel assignment, open label	NCT02943889	Not yet recruiting
14	2009	Umbilical cord	Allogeneic	Portal vein or hepatic artery	Unknown	LC	200	48 weeks	Phase 1–2	Randomized, parallel assignment, single blind (subject)	NCT01233102	Suspended
15	2009	Bone marrow	Autologous	Portal vein	Unknown	LC (HBV)	60	48 weeks	Phase 2	Non-randomized, parallel assignment, open label	NCT00993941	Unknown
16	2010	Umbilical cord	Allogeneic	Hepatic artery	Unknown	LC	50	4 weeks	Phase 1–2	Randomized, parallel assignment, open label	NCT01224327	Unknown
17	2013	Bone marrow	Autologous	Hepatic artery	1.0 × 106/kg	LC	30	12 weeks	Phase 3	Non-randomized, single group assignment, open label	NCT01854125	Enrolling by invitation
18	2012	Umbilical cord	Allogeneic	Hepatic artery	1.0 × 106/kg	LC (HBV)	240	48 weeks	Phase 1–2	Randomized, parallel assignment, open label	NCT01728727	Unknown
19	2013	Umbilical cord or bone marrow	Allogeneic	Peripheral vein	1.0 × 105/kg, 1.0 × 106/kg or 1.0 × 107/kg, 8 times	Liver failure (HBV)	210	72 weeks	Phase 1–2	Randomized, parallel assignment, open label	NCT01844063	Recruiting
20	2016	Umbilical cord	Allogeneic	Peripheral vein	4 or 8 times	ACLF (HBV)	261	52 weeks	Phase 2	Randomized, parallel assignment, open label	NCT02812121	Not yet recruiting
21	2010	Menstrual blood	Allogeneic	Peripheral vein	1.0 × 106/kg, 4 times	LC	50	48 weeks	Phase 1–2	Randomized, single group assignment, open label	NCT01483248	Enrolling by invitation
22	2008	Bone marrow	Autologous	Hepatic artery	Unknown	LC	50	96 weeks	Phase 2	Randomized, parallel assignment, single blind (subject)	NCT00976287	Unknown
23	2012	Bone marrow	Autologous	Hepatic artery	5 × 107/patient, 1 time or 2 times	LC (alcohol)	72	24 weeks	Phase 2	Randomized, parallel assignment, open label	NCT01875081	Completed	Histological improvement. Improvement in AST, ALT, ALP, γ-GTP, Child-Pugh score, and MELD score.	16
24	2014	Bone marrow	Autologous	Peripheral vein	Unknown	LC	10	24 weeks	Phase 1	Non-randomized, single group assignment, open label	NCT02327832	Recruiting
25	2005	Bone marrow	Autologous	Hepatic artery	3.4 × 108/patient	Liver failure (HBV)	158	192 weeks	Phase 1–2	Case control, retrospective	NCT00956891	Completed	Improvement in Alb, T-Bil, PT, and MELD score.
26	2009	Umbilical cord	Allogeneic	Peripheral vein	5.0 × 105/kg, 3 times	LC	45	48 weeks	Phase 1–2	Randomized, parallel assignment, open label	NCT01220492	Unknown	Improvement in Alb, T-Bil, and MELD score. Reduction of ascites.	17
27	2010	Bone marrow	Autologous	Portal vein	1.4–2.5 × 108/patient, 2 times	LC	2	48 weeks	Phase 1	Non-randomized, single group assignment, open label	NCT01454336	Completed	Transient improvement in MELD scores.	18
28	2007	Bone marrow	Autologous	Peripheral vein	(1.2–2.95 × 108) 1.95 × 108/patient	LC	27	48 weeks	Unknown	Randomized, parallel assignment, double blind (subject, outcomes assessor)	NCT00476060	Unknown	No beneficial effect.	19
29	2011	Bone marrow	Allogeneic	Hepatic artery and peripheral artery	1.0 × 106/kg (5.0 × 107 cells via the hepatic artery and the remaining cells via the peripheral vein)	Wilson’s disease	10	24 weeks	Unknown	Non-randomized, single group assignment, open label	NCT01378182	Completed
30	2016	Umbilical cord or bone marrow	Allogeneic	Portal vein or hepatic artery	2.0 × 107/patient, 4 times	LC	20	48 weeks	Phase 1	Non-randomized, single group assignment, open label	NCT02652351	Recruiting
31	2016	Bone marrow	Autologous	Hepatic artery	5 × 107/patient, 1 time or 2 times	LC (alcohol)	50	144 weeks	Phase 2	Randomized, parallel assignment, open label	NCT02806011	Enrolling by invitation
32	2011	Umbilical cord	Allogeneic	Peripheral vein	1.0 × 106/kg, 3 times	Liver failure (AIH)	100	96 weeks	Phase 1–2	Randomized, parallel assignment, open label	NCT01661842	Unknown
33	2009	Adipose tissue	Autologous	Unknown	Unknown	LC	6	24 weeks	Phase 1	Non-randomized, single group assignment, open label	NCT00913289	Terminated
34	2012	Adipose tissue	Autologous	Hepatic artery	Unknown	LC	4	4 weeks	Unknown	Non-randomized, single group assignment, open label	NCT01062750	Completed
35	2016	Umbilical cord	Allogeneic	Lobe	5.0 × 108/patient	LC	40	96 weeks	Phase 1–2	Randomized, parallel assignment, double blind (subject, outcomes assessor)	NCT02786017	Recruiting
36	2011	Bone marrow	Unknown	Peripheral vein	5.0–50 × 106/kg	LC (PBC)	20	96 weeks	Phase 1	Randomized, parallel assignment, open label	NCT01440309	Unknown
37	2011	Umbilical cord	Allogeneic	Peripheral vein	5.0 × 105/kg, 3 times	LC (PBC)	7	48 weeks	Phase 1–2	Randomized, parallel assignment, open label	NCT01662973	Unknown	Improvement in Alb, T-Bil, and MELD score. Reduction of ascites.	20
38	2010	Bone marrow	Allogeneic	Portal vein or hepatic artery	Unknown	Liver failure (HBV)	60	48 weeks	Phase 2	Non-randomized, parallel assignment, open label	NCT01221454	Unknown
39	2010	Bone marrow	Allogeneic	Portal vein or hepatic artery	Unknown	LC	60	48 weeks	Phase 2	Non-randomized, parallel assignment, open label	NCT01223664	Unknown
40	2010	Bone marrow	Autologous	Hepatic artery	(0.25–1.25 × 106) 0.75 × 106/patient	LC (HBV)	39	24 weeks	Phase 2–3	Non-randomized, parallel assignment, open label	NCT01560845	Unknown	Decrease in Th-17 cells, RORγt, IL-17, TNF-α, and IL-6. Increase in Tregs and Foxp3.	21

LC liver cirrhosis, ACLF acute-on-chronic liver failure, HBV hepatitis B virus, HCV hepatitis C virus, AIH autoimmune hepatitis, PBC primary biliary cholangitis, MELD Model for End-Stage Liver Disease, AST aspartate transaminase, ALT alanine transaminase, ALP alkaline phosphatase, γ-GTP gamma-glutamyl transpeptidase, Alb albumin, T-bill total bilirubin, PT prothrombin time, PC protein C, ROR RAR-related orphan receptor, Foxp3 forkhead box P3, IL interleukin, Th T helper, SMA smooth muscle actin, TGF transforming growth factor, TNF tumor necrosis factor

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