scholarly journals Regenerative Therapy for Liver Cirrhosis Based on Intrahepatic Arterial Infusion of Autologous Subcutaneous Adipose Tissue-Derived Regenerative (Stem) Cells: Protocol for a Confirmatory Multicenter Uncontrolled Clinical Trial (Preprint)

2020 ◽  
Author(s):  
Yoshio Sakai ◽  
Shinya Fukunishi ◽  
Masayuki Takamura ◽  
Oto Inoue ◽  
Shinichiro Takashima ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Liver Cirrhosis ◽  
Data Analysis ◽  
Albumin Concentration ◽  
Safety And Efficacy ◽  
Tissue Dissociation ◽  
Primary Endpoints ◽  
Clinical Trials Registry

BACKGROUND Liver cirrhosis results from chronic hepatitis, and is characterized by advanced fibrosis due to long-term hepatic inflammation. Cirrhosis ultimately leads to manifestations of jaundice, ascites, and encephalopathy, and increases the risk of hepatocellular carcinoma. Once cirrhosis is established, resulting in hepatic failure, no effective treatment is available. Therefore, novel therapies to inhibit disease progression of cirrhosis are needed. OBJECTIVE The objective of this investigator-initiated clinical trial is to assess the safety and efficacy of autologous adipose tissue-derived regenerative (stem) cell therapy delivered to the liver via the hepatic artery in patients with liver cirrhosis. METHODS Through consultation with the Japan Pharmaceuticals and Medical Devices Agency, we designed a clinical trial to assess a therapy for liver cirrhosis based on autologous adipose tissue-derived regenerative (stem) cells, which are extracted using an adipose tissue dissociation device. The primary endpoints of the trial are the serum albumin concentration, prothrombin activity, harmful events, and device malfunction. RESULTS Enrollment and registration were initiated in November 2017, and the follow-up period ended in November 2019. Data analysis and the clinical study report will be completed by the end of March 2020. CONCLUSIONS Completion of this clinical trial, including data analysis, will provide data on the safety and efficacy of this novel liver repair therapy based on autologous adipose tissue-derived regenerative (stem) cells using an adipose tissue dissociation device. CLINICALTRIAL UMIN Clinical Trials Registry UMIN000022601; https://tinyurl.com/w9uqw3q INTERNATIONAL REGISTERED REPORT DERR1-10.2196/17904

scholarly journals Regenerative Therapy for Liver Cirrhosis Based on Intrahepatic Arterial Infusion of Autologous Subcutaneous Adipose Tissue-Derived Regenerative (Stem) Cells: Protocol for a Confirmatory Multicenter Uncontrolled Clinical Trial

10.2196/17904 ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. e17904 ◽  
Author(s):  
Yoshio Sakai ◽  
Shinya Fukunishi ◽  
Masayuki Takamura ◽  
Oto Inoue ◽  
Shinichiro Takashima ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Liver Cirrhosis ◽  
Data Analysis ◽  
Albumin Concentration ◽  
Safety And Efficacy ◽  
Tissue Dissociation ◽  
Primary Endpoints ◽  
Clinical Trials Registry

Background Liver cirrhosis results from chronic hepatitis, and is characterized by advanced fibrosis due to long-term hepatic inflammation. Cirrhosis ultimately leads to manifestations of jaundice, ascites, and encephalopathy, and increases the risk of hepatocellular carcinoma. Once cirrhosis is established, resulting in hepatic failure, no effective treatment is available. Therefore, novel therapies to inhibit disease progression of cirrhosis are needed. Objective The objective of this investigator-initiated clinical trial is to assess the safety and efficacy of autologous adipose tissue-derived regenerative (stem) cell therapy delivered to the liver via the hepatic artery in patients with liver cirrhosis. Methods Through consultation with the Japan Pharmaceuticals and Medical Devices Agency, we designed a clinical trial to assess a therapy for liver cirrhosis based on autologous adipose tissue-derived regenerative (stem) cells, which are extracted using an adipose tissue dissociation device. The primary endpoints of the trial are the serum albumin concentration, prothrombin activity, harmful events, and device malfunction. Results Enrollment and registration were initiated in November 2017, and the follow-up period ended in November 2019. Data analysis and the clinical study report will be completed by the end of March 2020. Conclusions Completion of this clinical trial, including data analysis, will provide data on the safety and efficacy of this novel liver repair therapy based on autologous adipose tissue-derived regenerative (stem) cells using an adipose tissue dissociation device. Trial Registration UMIN Clinical Trials Registry UMIN000022601; https://tinyurl.com/w9uqw3q International Registered Report Identifier (IRRID) DERR1-10.2196/17904

scholarly journals Clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for exploration of its safety and efficacy

2021 ◽  
Vol 18 ◽  
pp. 97-101
Author(s):  
Yoshio Sakai ◽  
Shinya Fukunishi ◽  
Masayuki Takamura ◽  
Kazunori Kawaguchi ◽  
Oto Inoue ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Safety And Efficacy ◽  
Stem Cells Therapy

Cell-Based Regenerative Endodontics for Treatment of Periapical Lesions: A Randomized, Controlled Phase I/II Clinical Trial

2020 ◽  
Vol 99 (5) ◽  
pp. 523-529 ◽  
Author(s):  
C. Brizuela ◽  
G. Meza ◽  
D. Urrejola ◽  
M.A. Quezada ◽  
G. Concha ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Phase I ◽  
Umbilical Cord ◽  
Root Canal ◽  
Categorical Variables ◽  
Safety And Efficacy ◽  
Randomized Controlled

A randomized controlled phase I/II clinical trial was designed to evaluate the safety and efficacy of encapsulated human umbilical cord mesenchymal stem cells in a plasma-derived biomaterial for regenerative endodontic procedures (REPs) in mature permanent teeth with apical lesions. The trial included 36 patients with mature incisors, canines, or mandibular premolars showing pulp necrosis and apical periodontitis. Patients were randomly and equally allocated between experimental (REP) or conventional root canal treatment (ENDO) groups. On the first visit, cavity access and mechanical preparation of the root canal were performed. Calcium hydroxide medication was used, and the cavity was sealed. Three weeks later, patients were treated following their assigned protocol of ENDO or REP. Clinical follow-up examinations were performed at 6 and 12 mo. Categorical variables were evaluated by Fisher’s exact test. Quantitative variables were compared using the Mann-Whitney test. The evolution over time of the percentage of perfusion units and the dimensions of lesion and cortical compromise were explored. After the 12-mo follow-up, no adverse events were reported, and the patients showed 100% clinical efficacy in both groups. Interestingly, in the REP group, the perfusion unit percentage measured by laser Doppler flowmetry revealed an increase from 60.6% to 78.1% between baseline and 12-mo follow-up. Sensitivity tests revealed an increase of the positive pulp response in the REP group at 12-mo follow-up (from 6% to 56% on the cold test, from 0% to 28% on the hot test, and from 17% to 50% on the electrical test). We present the first clinical safety and efficacy evidence of the endodontic use of allogenic umbilical cord mesenchymal stem cells encapsulated in a plasma-derived biomaterial. The innovative approach, based on biological principles that promote dentin-pulp regeneration, presents a promising alternative for the treatment of periapical pathology (ClinicalTrials.gov NCT03102879).

scholarly journals ID: 1055 Adipose-derived stem cells and platelet rich plasma ameliorate liver cirrhotic circumstance in CCl4-induced mice: a new approach for liver cirrhosis treatment

2017 ◽  
Vol 4 (S) ◽  
pp. 136
Author(s):  
Nhung Hai Truong ◽  
Nam Hai Nguyen ◽  
Trinh Van Le ◽  
Nghia Huynh ◽  
Dat Quoc Ngo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Liver Cirrhosis ◽  
Platelet Rich Plasma ◽  
Ldl Receptor ◽  
Cell Types ◽  
Cirrhotic Liver ◽  
Induction Medium ◽  
Adipose Derived Stem Cells ◽  
Cell Sources

Background: Stem cell therapy in liver cirrhosis treatment is attracting the attention of the scientific community. Adipose tissue-derived mesenchymal stem cells are a potential source of cells because they have self-renewal, high proliferation, and differentiation into a variety of cell types, including hepatocytes as potential cell sources for cirrhosis treatment. Platelet-rich plasma (PRP) growth factors contribute to regeneration and wound healing. We test the hypothesis that PRP co-administration enhances MSC treatment for mouse cirrhosis. Method: Male Swiss mice were treated orally with olive oil or CCl4 for 11 weeks. PRP was obtained from healthy mice. Mouse adipose-derived stem cells (mADSCs) from adipose tissue of 3 weeks CCl4 mice were cultured for three passages (P3-mADSCs) before the transfer by tail vein injection with or without PRP into 11 weeks CCl4 mice. Mice were divided into six groups (n=10 each group). 1) normal, 2) cirrhotic, 3) cirrhotic /PBS; 4) cirrhotic/PRP (0.2 ml/mice with PRP from healthy mice), 5) cirrhotic/mADSCs (5 x 105 cells/mice), and 6) cirrhotic/mADSC-PRP.   Result: mADSCs were highly positive for CD44, CD90, and CD105. Relative to liver cells, P3-mADSCs highly expressed Alb, Ck18, Ck19, Tnf, c-met, Cyp1a1, Afp, Muc1, Ldl receptor. mADSCs were strongly positive for Cyp1a1 (98.21±1.57%) and Hgf (95.55±3.11%); moderately positive for alfa-fetoprotein (45.99±2.08%), Aat (44.43±7.79%), Alb (57.81±8.49%) and differentiated into hepatocyte-like cells under induction medium. After transplantation, CFDA-transplanted cells into CCl4-treated mice were found in the liver at day 21 st. Compared to mADSCs, mADSCs and PRP co-treatment most effectively improved serum AST/ALT/bilirubin and albumin levels in day seven cirrhotic mice (p<0.05); and significantly down-regulated procollagen (104-fold less) and TGF-beta 1 (10-fold less) in day 21 cirrhotic liver. Histology index and collagen deposition were improved in 100% of mADSC/PRP- and mADSCs- cirrhotic mice compared to 33.3% of PBS- or PRP- cirrhotic liver (p<0.05). Conclusion: Cultured mADSCs express hepatocyte enriched markers. PRP coadministration enhances mADSC effects to improve liver function further, and further reduce fibrosis.

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